Äîêóìåíò âçÿò èç êýøà ïîèñêîâîé ìàøèíû. Àäðåñ îðèãèíàëüíîãî äîêóìåíòà : http://www.chem.msu.ru/eng/misc/babaev/papers/132e.pdf Äàòà èçìåíåíèÿ: Thu Jan 20 18:51:48 2011 Äàòà èíäåêñèðîâàíèÿ: Sat Feb 12 03:15:55 2011 Êîäèðîâêà:

Russian Chemical Bulletin, International Edition, Vol. 57, No. 4, pp. 845--862, April, 2008

845

Oxazolo[3,2 a]pyridinium and oxazolo[3,2 a]pyrimidinium salts in organic synthesis
E. V. Babaev, V. L. Alifanov, and A. V. Efimov Department of Chemistry, M. V. Lomonosov Moscow State University, 1 Leninskie Gory, 119991 Moscow, Russian Federation. Fax: +7 (495) 932 8846. E mail: babaev@org.chem.msu.ru
The methods for the synthesis of oxazolo[3,2 a]pyridinium and oxazolo[3,2 a]pyrimidinium salts and their reactivities are reviewed. Both systems exhibit ambident properties in reactions with nucleophiles; depending on the substituents and the reagents, both the oxazole and azine rings can undergo opening and transformations. A number of new methodologies involving oxazolopyridini um and oxazolopyrimidinium salts for the design of functionalized oxazoles, imidazoles, fused pyrroles, and other heterocyclic systems are generalized. Key words: recyclization, oxazole, pyridine, pyrimidine, pyrrole, indolizine, fused rings.

One of the main features of aromatic heterocycles is their tendency (in contrast to carbocycles) toward het erolytic ring opening via cleavage of a carbon--heteroat om bond. The resulting acyclic fragment is often capable of undergoing cyclization into a new ring. As a rule, such a recyclization of one heterocycle into another is a single step process leading to otherwise inaccessible structures with unusually arranged functional groups. The well known examples of recyclization include the Yur´ev reac tion, the Hafner reaction, and the Dimroth, Kost--Sa gitullin, and Boulton--Katritzky rearrangements.1 A num ber of our reviews2--4 have been devoted to the general structural classification of recyclization reactions. Recy clization is widely used in modern organic synthesis as a nontrivial strategy for the targeted preparation of bio logically active compounds, dyes, and compounds with other valuable properties. A search for new recyclization examples is still of current interest for organic chemists. In the general case, bond cleavage in a monocyclic heterocycle can involve different positions of the ring to give various acyclic compounds (or recyclization prod ucts). Opening of fused rings consisting of at least two fused heterocycles can follow a more complicated pat tern. In this case, any of the annulated heterocycles can undergo opening and recyclization so that the opening pathway is difficult to predict. An interesting model sys tem with dissimilar rings capable of opening and recy clization is the class of cationoid heteroaromatic systems 1 with the bridgehead nitrogen atom, in which the ox azole fragment is fused with the pyridine (X = CH) or pyrimidine ring (X = N). It is well known that mono cyclic oxazolium, pyridinium, and pyrimidinium cations readily undergo ring opening under the action of various nucleophiles; in bicyclic salts 1, competitive opening of

the azole and azine rings seems to be possible (Scheme 1, also see the reviews5--7).
Scheme 1

Potentially ambident cations 1 could serve as promis ing reagents for the synthesis of various classes of hetero cycles (substituted azoles, azines, and azoloazines). The present review is devoted to development of synthetic routes to fused systems 1, study of the regularities and the factors that influence the regioselectivity of ring open ing, and ways of controlling such processes. 1. Methods for the synthesis of oxazolo[3,2 a]pyridinium salts 1.1. Known strategies Oxazolo[3,2 a]pyridinium salts 2 were first obtained from N phenacyl 2 pyridones 3 in the presence of conc. H2SO4 according to reaction 2a (Scheme 2).8,9

Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 4, pp. 831--848, April, 2008. 1066 5285/08/5704 0845 © 2008 Springer Science+Business Media, Inc.


846

Russ.Chem.Bull., Int.Ed., Vol. 57, No. 4, April, 2008

Babaev et al.

Scheme 2

X = Cl, Br

Reagents and conditions: (2a) H2SO4, HClO4; (2b) R´3N or pi coline; (2c) Br2, , R = H; (2d) HBr, Ac2O.

Later, this system was alternatively synthesized by a reaction of 2 halo 1 phenacylpyridinium salts 4 with

various tertiary amines:10,11 triethylamine, N,N dime thylaniline, diisopropyl(ethyl)amine, or picoline (re action 2b). Bicyclic compound 2 can also be constructed in two other (less common) ways: closure of an oxazole ring from 2 (vinyloxy)pyridine12 (reaction 2c) and clos ure of a pyridine ring in reaction 2d (see Ref. 13). It should be noted that reaction 2b has been recently14,15 modified by using sulfur containing pyridinium salts 5 instead of halopyridinium salts 4 (Scheme 3, reaction 3). A version of this reaction involves immobilization of the above salts on the solid phase support. We found another, very unusual example of the forma tion of an oxazolopyridinium salt in a reaction of a thiaz olopyridinium salt with an aromatic amine16,17 (Scheme 4). Compound 6 was isolated which turned out to be a complex of an oxazolopyridinium salt with 4 bromo aniline (X ray diffraction data). During the reaction, the framework of the starting reagent loses the fragment MeSCS. The unexpected formation of the oxazole ring from the thiazole one can be explained only by the forma tion of intermediate N phenacylpyridinium betaine (e.g., A)

Scheme 3

X = Cl, Br RHal = MeI or the Merrifield resin

Scheme 4

6

A


Oxazolo[3,2 a]pyri(mi)dinium salts

Russ.Chem.Bull., Int.Ed., Vol. 57, No. 4, April, 2008

847

that undergoes cyclization by eliminating a leaving group from the position (dithiocarbamate residue). 1.2. Synthesis of oxazolo[3,2 a]pyridinium salts by cyclization of N substituted pyridones Among the aforementioned synthetic strategies leading to oxazolopyridinium salts 2 (see Schemes 2--4), pathway 2a involving cyclization of N (2 oxoethyl)pyridones 3 should be preferred. As a rule, the residue CH2COR at the nitrogen atom is the phenacyl group. Closure of the ox azole ring in such pyridones easily occurs in conc. H2SO4 (such a cyclization is analogous to the Gabriel synthesis of monocyclic oxazoles) and the resulting salts can be easily isolated as insoluble perchlorates. This cyclization can be complicated by the sulfonating ability of H2SO4. For in stance, an attempted synthesis of an oxazolopyridinium salt containing a p anisyl residue at the C(2) atom gave a sulfo derivative and in a cyclization of pyridone with a diphenyl residue, sulfonation was prevented only by care ful heating of the reaction mixture in conc. HClO4.9 Ana logous cyclizations of benzopyridones proceed smoothly for isoquinolone (Scheme 5, reaction 5a).9 In the case of quinolones, they follow usual (reaction 5b)9 or anom alous pathways (reaction 5c),18 depending on the pres ence of electron donating substituents in the phenacyl residue. We studied the possibility of obtaining in this way various oxazolopyridinium salts containing aromatic, al iphatic, arylaliphatic, and heterocyclic substituents in the five membered ring and (cyclo)alkyl substituents and/or electron withdrawing substituents in the six mem

bered ring (Scheme 6, Table 1). The yields from these cyclocondensations are usually very high (sometimes, up to 100%). In some cases, addition of an equimolar amount of 30% oleum to H2SO4 was efficient. The structures of the resulting salts were unambiguously confirmed by 1H NMR data: upon the aromatization, the signal for N-- CH2 of pyridone (2 H intensity) changes into a low field singlet for the H(3) atom of oxazole (1 H intensity) (see Table 1). The structures of 12 perchlorates were proved by X ray diffraction analysis.
Scheme 6

For pyridones with labile (under acid hydrolysis con ditions) substituents, side processes could be expected. It turned out that the cyclization rates of N phenacyl deriv atives of 2 oxonicotinonitrile, 2 oxonicotinamide, and ethyl 2 oxonicotinate (Scheme 7) are higher than the hydrolysis rates of their functional groups.23,32 However, the cyclization rates of the cyclic homologs of such compounds were lower than their hydrolysis rates; as the result, the cyclization of nitriles yielded amides33--35 (Scheme 8).

Scheme 5

Reagents: H2SO4, HClO4.


848

Russ.Chem.Bull., Int.Ed., Vol. 57, No. 4, April, 2008

Babaev et al.

Table 1. Synthesis of oxazolopyridinium salts 2 and the starting pyridones 3 Substituents R2 H H H H Me Me Me Me Me Me Me (CH (CH (CH (CH (CH Me Me Me Me (CH2) (CH2) (CH2) H H H H H H H H
a b c
3 4 5 2)3 2)4 2)5 2)6 2)4

Salt 2 R
5

Pyridone 3 H(3), 8.63 8.70 8.87 8.92 8.50c 8.86c 8.50c 9.49 9.58 9.68 9.42 9.33 9,37 9.58 9.52 9.63 9.72 9.61 9.43 9.51 9.50 9.52 9.76 9.11 9.18 9.13 8.64 8.71 8.56 8.61 8.63
a

References

R

3

R

4

R1 C6H5 p Br6H4 m NO26H4 p NO26H4 p Br6H4 p NO26H4 C6H5 p Cl6H4 3,4 Cl26H3 p NO26H4 p Br6H4 p Cl6H4 p Cl6H4 p Cl6H4 p Cl6H4 p NO26H4 p Cl6H4 p Br6H4 p Br6H4 p Br6H4 p Cl6H4 p Cl6H4 p Cl6H4 p 6H4 p NO26H4 p Cl6H4 p ClC6H4CH2 p NO2C6H4CH Me Et 4 Py

Yield (%) 83 89 68 70 79 69 72 46 88 83 90 98 98 97 96 95 92 82 74 81 97 98 96 94 66 95 87 84 42 67 96

Yield (%) 85 87 92 80 (71)b (62)b (51)b (54)b 31 57--67 14 48 27 39 38 42 40 58 42 55 6 42 34 24 45 43 21 51 38 79 90 91 67 52 95

Reaction 9a 9a 9a 9a 9c 9c 9c 9c 9c 9c 9c 9c 9c 9c 9c 9c 9c 9j 9j 9j 9j 9j 9j 9j 9j 9j 13 13 13 13 13 19--21

H H H H H H H H H H (CH2)4

H H H H H H H H H Me Me Me Me Me Me Me Me Me Me H H H H H H H H H H H

NO H H H

2

NO NO NO H H H H H

2 2 2

H H H H H H H H H H H H H H H H H CN CONH CO2Et CONH CONH CONH H H H H H H H H

21--23

24, 25 26, 27 28, 29 27, 30 31 28 17 23, 32 23 23 33 34 35 36

2

2 2 2

16, 37

2

In DMSO d6. In CF3COOH. The yield of chloropyridinium salt 4 is given in parentheses. In CF3COOH. Scheme 7

1.3. Distinctive features of the synthesis of intermediate N (2 oxoethyl)pyridones 3 Since these are N (2 oxoethyl)pyridones 3 that are key intermediates in the preparation of bicyclic oxazolopyri dinium salts (see Scheme 6), let us briefly consider the methods of their synthesis (Scheme 9, see Table 1). The simplest route to pyridones 3 involves the hydro lysis of 2 halopyridinium salts 4 (Scheme 9, reaction 9a).19,20 Salts 4 can be easily prepared by quaternization of 2 halopyridines (reaction 9b); however, this method is unsuitable for sterically hindered pyridines.22 An efficient route to pyridones 3 containing a second substituent involves N alkylation of 2 methoxy pyridines (reaction 9c). In this case, the OMe group serves as a protective function and the reaction is ac companied by demethylation. 2 Methoxypyridines are easily prepared from 2 halopyridines and sodium meth

R = CN, CONH2, CO2Et

Reagents and conditions: H2SO4, HClO4, 30 min. Scheme 8


Oxazolo[3,2 a]pyri(mi)dinium salts

Russ.Chem.Bull., Int.Ed., Vol. 57, No. 4, April, 2008

849

Scheme 9

Scheme 11

B is a base

matographically mobile, which allows easy isolation of the N isomers 3 in the individual state.
Scheme 12

X = Cl, Br

Reagents: (9a) NaOH, H2O/EtOH; (9b, 9c) R´COCH 2Br; (9d) H3O+; (9e) MeONa/MeOH; (9f) POCl3; (9g) Ag2CO3, MeI; (9h) NaOH/ClCH2COOH; (9i) Ac2O/HClO4, R3N/R´COCl; (9j) 1) NaOH, H2O/EtOH, 2) R´COCH2Br.

oxide (reaction 9e) or by methylation of silver pyridinolates (reaction 9g). We employed this strategy to obtain a large number of alkylpyridones 3 (and their cyclic ho mologs)22,23,25,27 and the corresponding salts 2 (Scheme 10). Sterically hindered 2 alkyl 6 methoxypyridines are alkylated in moderate to high yields (see Table 1).
Scheme 10

X = CN, CONH2, CO2Et B is a base

Direct phenacylation of sodium salts of pyridones (re action 9j) was efficient to obtain pyridones 3 containing an electron withdrawing substituent in the ring. For in stance, alkali metal salts of 5 nitro 2 pyridone are alkylat ed regioselectively at the N atom (Scheme 11).36 Alkylation of pyridones combining an electron with drawing group in the position and a second substi tuent (methyl group or an alicyclic fragment), gives mixtures of O and N phenacyl derivatives (Sche me 12).23,35,38 Preparatively, such mixtures are not diffi cult to separate: the O isomers are more soluble and chro

The last strategy in the synthesis of pyridones 3 in volves hydrolytic opening of the oxazolone ring in me soionic oxazolopyridinium 2 olates 7 (see Scheme 9, re action 9d).37,39,40 Bicyclic mÝnchnones 7 are prepared from (2 oxopyridyl)acetic acid and acid anhydrides (chlo rides) (Scheme 13). Structurally, the overall sequence of transformations in Scheme 13 resembles the Dakin--West conversion of an amino acid into an amino ketone, provided that (2 oxopyridyl)acetic acid is regarded as a peculiar amino acid. This step sequence has a number of distinct advan tages over the methods discussed above (see Scheme 9, reactions 9a, 9c, 9j and Schemes 10--12). First, no lach rymatory bromo ketones are employed; second, the re sulting pyridones can contain at the N atom such a methyl ketone residue (e.g., that of benzyl methyl ketone or 4 acetylpyridine) that is otherwise difficult (or impossible) to introduce into structure 3. Thus, Scheme 6 provides a reliable route to oxazolopy ridinium salts 2 starting from N substituted pyridones 3, which in turn can be prepared in various ways. This meth


850

Russ.Chem.Bull., Int.Ed., Vol. 57, No. 4, April, 2008

Babaev et al.

Scheme 13

pounds leading to cationoid bicycles is well known, being a general method for their synthesis.42,43 We used this strategy17 in the synthesis of novel ox azolopyrimidinium salt 9 containing no substituent in the pyrimidine fragment: the target salt was obtained by condensation of 2 amino 4,5 dimethyloxazole with ma londialdehyde acetal (reaction 14b). 2.2. Synthesis from pyrimidines An alternative route to the salts in question (construc tion of an oxazole ring on the pyrimidine one) has been described by Liebscher group.44,45 The key intermediate was N phenacylpyrimidine 2 thione prepared in a rather unusual fashion (Scheme 15); such pyrimidinethiones were converted in two different ways (15a and 15b) into oxazolo[3,2 a]pyrimidinium salts 10. It should be em phasized that the chemical properties of salts 8 and 10 have not been studied in the cited papers.41,44,45 During the multistep transformation (see Scheme 15), the pyrimidine fragment of the target oxazolopyrimidines 10 is originally assembled in a very complicated way, presenting a striking contrast to the simple reaction se quence in the synthesis of their pyridine analogs 2 : pyridinesN alkylpyridonesoxazolopyridinium salts. We wondered whether oxazolopyrimidinium salts could be directly obtained from easily accessible pyrimidone (by analogy with the aforesaid tandem of reactions shown in Schemes 6 and 9 (reaction 9j)). It turned out (Table 2) 46 that alkali metal salts of 2 pyrimidone undergo high yielding regioselective N phenacylation (Scheme 16, reaction 16a). The IR spec tra of the resulting compounds 11 contain two groups of CO vibrations (CH2C=O and N--C=O). The struc ture of one N isomer was confirmed by X ray diffrac tion analysis.47

i. Et3N, (RCO2)O or Et3N, RCOCl

odology allows broad variation of the nature of the substituents in the pyridine and oxazole fragments of salts 2. 2. Methods for the synthesis of oxazolo[3,2 a]pyrimidinium salts 2.1. Synthesis from oxazoles Oxazolo[3,2 a]pyrimidinium salts, which are aza ana logs of salts 2, can be obtained by constructing the second ring on both oxazoles and pyrimidines. Condensation of accessible 2 aminooxazoles with acetylacetone gave salts 8a,b (Scheme 14, reaction 14a).41 Condensation of ami noazoles and aminoazines with 1,3 dicarbonyl com
Scheme 14

Table 2. Synthesis of oxazolopyrimidinium salts from 2 pyrimidone46 Ar Pyrimidone 11 Yield (%) p ClC6H4 p BrC6H4 p NO2C6H4 C6H5 p CH3C6H4 p CH3OC6H4
a b c d

Salt 12
a
2

NCH

Yield (%)b 90 85 80 55 (79) 75c

H(3) a

90 95 65 79 81 70

5.48 5.43 5.55 5.50 5.45 5.40

c

9.31 9.31 9.50 9.81d 9.20

Reagents and conditions: (14a) HCl, R = Ph (8a), Me (8b); (14b) HCl, , HClO4, R = Me.

DMSO d6. H2SO4 + SO3. CF3SO3H/P2O5. CF3COOD.


Oxazolo[3,2 a]pyri(mi)dinium salts

Russ.Chem.Bull., Int.Ed., Vol. 57, No. 4, April, 2008

851

Scheme 15

X = I, ClO4

Scheme 16

the bicycle can be varied by using different synthetic strat egies. 3. Structure and reactivity of oxazolopyridinium salts 3.1. Structure of salts 2 It follows49 unambiguously from X ray diffraction data for salts 2 that the pyridine fragment of the bicyclic com pound exhibits a slight quasidiene character. Therefore,

Reagents and conditions: (16a) ArCOCH2Br, K2CO3--Me2CO, 20 °C, 48 h; (16b) Ar = p ClC6H4, HClO4/Ac2O or H2SO4/HClO4, or polyphosphoric acid/HClO4; ( 16c) H2SO 4·SO3/HClO4, CF3SO3H--P2O5, HClO4--H2O, Ar = Ph, p MeC6H4.

Cyclocondensation of compounds 11 into salts 12 has been carried out46 under the action of oleum. With H2SO4 or polyphosphoric acid, reaction 16b stops at the proto nation step. To avoid sulfonation for Ar = Ph and p MeC6H4, we used CF3SO3H--P2O5 as an efficient de hydrating agent. The 1H NMR spectra of salts 12 show a characteristic low field signal for the oxazole proton at 9.2--9.8; the structure of one salt was proved by X ray diffraction analysis.48 Thus, the above strategies allow oxazolopyrimidini um salts to be obtained from both oxazoles and pyrim idines. The substituents in positions 2, 3, 5, and 7 of


852

Russ.Chem.Bull., Int.Ed., Vol. 57, No. 4, April, 2008

Babaev et al.

the structure of this aromatic system is accurately de scribed by superposition of resonance structures 2A and 2B (not 2C) with the positive charge delocalized over the chain of the atoms N--C(9)--O. According to quantum chemical calculations,20,21,50,51 the greatest positive charge is localized on the bridgehead C(9) atom. That is why nucleophiles should be expected to attack this position with subsequent opening of the oxazole ring. 3.2. Reactions of oxazolopyridinium salts 2 with nucleophiles Before our investigations, reactions of salts 2 with nu cleophiles included only a few documented examples (Scheme 17). It has been mentioned11 that the oxazole ring in salt 2 undergoes opening in the presence of alkali (reaction 17a) to give N phenacyl 2 pyridone in a nearly quantitative yield. In some cases, the opening of the ox azole ring was accompanied by closure of a new ring. For instance, prolonged reflux of salt 2 in n butylamine trans formed the oxazole ring into an imidazole one (reaction 17b) to give a 1 butyl 2 phenylimidazo[1,2 a]pyridinium salt;10 no analogous recyclization with aniline occurs. On short time reflux in n butylamine (10 min), the interme diate of this transformation can be isolated: this is a cyclic hydrate that undergoes dehydration and aromatization under the action of polyphosphoric acid. The formation of imidazo[1,2 a]pyridinium salts can be promoted by other primary amines.52 Reactions with phosphorus and arsenic containing nucleophiles (reactions 17c,d) afford very uncommon azolopyridines with the ring P or As atoms.53 Insofar as the range of the nucleophilic agents used was not representative enough, we studied reactions of salts 2 with simple O , N , S , and C nucleophiles. In all the cases, a nucleophilic attack follows an analogous pattern, with opening (and/or recyclization) of the ox azole ring (Scheme 18). Salts 2 reacted with sodium

Scheme 18

Com pound 13a 13b 14a 14b 14c 14d 15 16

R H Me H Me H H H Me

R´ Ph 3,4 Cl2C6H3 Ph p NO2C6H4 Py p ClC6H4CH2 Ph p NO2C6H4

Yield (%) 90 52 60--80 98 10 40 74 78

Reagents: (18a) NaSH; (18b) NH3/DMF; (18c) MeNO2, K2CO3; (18d) N2H4.

hydrosulfide23,51 (reaction 18a) to give the corresponding pyridinethiones 13, which are inaccessible (e.g., 13b) via direct N alkylation of pyridine 2 thione. Reactions of salts

Scheme 17

R = Bun, PhCH2


Oxazolo[3,2 a]pyri(mi)dinium salts

Russ.Chem.Bull., Int.Ed., Vol. 57, No. 4, April, 2008

853

2 with ammonia (reaction 18b) give, through the ring opening and recyclization steps, a new imidazole ring.23,37,51,54 5 Methylimidazopyridine 14b is obtained in a virtually quantitative yield. (An alternative synthesis by cyclocondensation of 2 amino 6 methylpyridine with phenacyl bromide affords this compound in very low yield.) Also note that imidazopyridines with the pyridyl (14c) or benzyl residues (14d) are difficult to obtain in an alternative way ( e.g. , according to the Chichibabin scheme). Reactions of salts 2 with nitromethane55 (reac tion 18c) result in the recyclization of the oxazole ring into a pyrrole one; this reaction is a new route to indoliz ines (nitroindolizine 15 is difficult to obtain by direct nitration of 2 phenylindolizine). Reaction 18d of salt 2 with hydrazine gives 1,4 dihydropyrido[2,1 c] 1,2,4 tri azinium perchlorate 16, which constitute an unusual het erocyclic system.54 The base--perchloric acid ratio in the product was 2 : 1. Interestingly, according to X ray diffraction data, the arrangement of the bicyclic struc tures in the crystal packing of compound 16 makes it impossible for pairs of its molecules to be linked by linear N--H--N hydrogen bonds. In reactions with the acetylacetonate anion, salts 2 undergo transformations into indolizines 17a,b (Sche me 19, pathway 19a).56 The reaction scheme involves a nucleophilic attack of a carbanion resulting in opening of the oxazole ring. In the reaction intermediate, an acetyl group acts as a carbonyl component in condensation with the methylene fragment of the N phenacyl residue. The proposed new scheme of construction of the indoliz ine framework can be formally regarded as the formation of two bonds, C(2)--C(3) and C(9)--C(1), in the pyrrole

fragment. With a homologous salt (pathway 19b), further cyclization of an analogous indolizine into cyclazine 17c could not be excluded. However, according to X ray dif fraction data,57 the reaction product was 1 acetyl 2,5 dimethylindolizine 17d (i.e., the formation of indolizine via closure of the pyrrole ring is accompanied by elimi nation of the p nitrobenzoyl residue, probably because of the steric hindrance created by the methyl group). For rational classification of the types of possible transformations of salts 2, we should introduce the fol lowing definitions.40 By convention, let nucleophiles be classified under the "XH type" if their anions contain at least one extra H atom (XH­ = OH­, SH­, RNH­, NO2CH2­, and Ac2CH­) or under the "X type" if the anion contains no extra proton (X­ = RO­ or R2N­). In all the reactions studied above, we used XH type nucleo philes. As the result, upon the ring opening in adduct 18a (Scheme 20), unstable ylide 18b can be stabilized by an extra proton of the XH group through tautomerization into covalent structure 18c. The atom at which subsequent cyclizations occur is determined by the nature of the residue X. Obviously, for X type nucleophiles, an analogous transformation of ylide 19 into any covalent structure is impossible. We found it interesting to study reactions of salts 2 with X type nucleophiles. It turned out that salts 2 react with such nucleophiles (alkoxide or secondary amines) in an uncommon way (Scheme 21). A reaction of salt 2 with sodium methoxide (reaction 21a) gives ketal 20,58 while reactions of salts 2 with secondary amines (reaction 21b) yields amino dienes 21 (Table 3).19--21

Scheme 19

Ar = Ph (17a), 55%; p NO2C6H4 (17b), 15%


854

Russ.Chem.Bull., Int.Ed., Vol. 57, No. 4, April, 2008

Babaev et al.

Scheme 20

Scheme 21

Dienes with the p nitrophenyl residue (in contrast to compounds containing other aryl substituents) are col ored deep dark cherry, probably because of intramo
Table 3. Characteristics of 1 amino 4 (oxazol 2 yl)buta 1,3 dienes (21) Ar X Yield (%) 67 70 68 81 96 62
max (log),

lecular charge transfer. In the mass spectra of amino dienes, the peak [M ­ NR2] is most intense (apparently, because of cyclization into aromatic cation 2). The stereochemis try of dienes, determined from NOESY spectra in C6D6 and X ray diffraction data,59 depends on the conditions for their synthesis and isolation. Short time stirring of the neat reagents at room temperature gives butadienes with the 1E,3Z configuration, while reflux of the reagents in MeCN yields 1E,3E dienes. On keeping the solutions of the dienes, the 1 E ,3 Z iso mer undergoes a slow transformation into the 1E,3E iso mer. The higher thermodynamic stability of the trans trans isomer is confirmed by quantum chemical calculations of the enthalpies of formation of the isomer ic molecules. Unusual opening of salts 2 in Scheme 21 should be associated with the fact that the formation of inter mediate ylide 19 (in the case of a nucleophilic attack on the C(9) atom) is thermodynamically unfavorable. As the result, the nucleophilic attack occurs either at the C(2) atom (for MeONa) followed by addition of a methanol molecule to the intermediate or at the C(5) atom (for amines) followed by opening of the ad duct into diene 21. Our quantum chemical calcula tions20,51,58 confirmed that the energies of the adducts and the open species depend on the nature of the nuc leophile. Interestingly, when oxazolopyridinium salts contain an additional nitro group in position 6, their reactivities change dramatically. An attack of not only second ary amines but also primary amines or ammonia (Sche me 22), as well as an attack of CH acids (Scheme 23), occurs always at the C(5) atom, giving oxazole deri vatives.17,36
Scheme 22

m/z (Irel (%)) M+ M ­ NR -- 276/274 (94/100) 241 (100) 241 (100) 241 (100) 241 (100)
2

EtOH

i. NuH (Nu = NH2, NHBu, piperidino, morpholino)

Ph p BrC6H4 m NO2C6H4 p NO2C6H4

CH2 CH2 CH2 CH2 (CH2)2 O

382 280 (4.38) (34) 391 360/358 (4.47) (46/40) 400 325 (4.37) (47) 464 325 (4.88) (63) 475 339 (4.33) (63) 439 327 (4.34) (40)

Thus, oxazolopyridinium salts 2 are promising reagents for the synthesis of unknown or difficult to obtain classes of organic compounds (Schemes 18, 19, and 21--23). Such salts are ambident systems capable of opening the oxazole or pyridine rings of the bicyclic molecule, depending o n the nucleophile (XH or X type) and the substituent in the pyridine fragment. It remains un clear how X type nucleophiles will react with homolo gous oxazolopyridinium salts 2 containing a methyl group at the C(5) atom that could present steric hindrances to an attack on the position 5.


Oxazolo[3,2 a]pyri(mi)dinium salts

Russ.Chem.Bull., Int.Ed., Vol. 57, No. 4, April, 2008

855

Scheme 23

Ar = p tolyl

3.3. Recyclization of 5 methyloxazolo[3,2 a]pyridinium salts into indolizines We found60 that salts 2 containing the methyl group in position 5 react with secondary amines in a very uncom mon way (Scheme 24). Instead of the expected amino dienes 22, we obtained representatives of the novel fami ly of 5 aminoindolizines 23.
Scheme 24

Scheme 25

The possible mechanism of this recyclization seems to involve an initial nucleophilic attack on the C(9) atom to give intermediate ylide (Scheme 25).21,23 The methyl group (acidic CH group) of the pyridinium ylide acts as a nucleophilic site in closure of a new five membered ring followed by aromatization of the pyrrole fragment. Using the 1H NMR technique, we detected an intermediate hy drate, which forms rapidly and undergoes slow dehydra tion.23

Apparently, in the reactions of salts 2 containing the 5 CH3 group with secondary amines, the regioselectivity changes because the methyl group creates steric hindrance to a nucleophilic attack on the C(5) atom. According to calculated data,21 the energy difference between the adducts at positions 5 and 9, which is small for 5 unsub stituted salts, increases substantially for 5 methyl deriva tives so that the formation of the adduct at the C(9) atom is more favorable.


856

Russ.Chem.Bull., Int.Ed., Vol. 57, No. 4, April, 2008

Babaev et al.

Variation of the secondary amine and the aryl residue in 5 methyloxazolopyridinium salts showed (Table 4) that reaction 26a is of general character and provides good yields.40 The stability of the resulting 5 aminoindoliz ines largely depends on the electron withdrawing nature of the aryl residue in position 2: for Ar = p NO2C6H4 or 3,4 Cl2C6H3, the indolizines are stable in storage; other wise, they rapidly oxidize in air.23,25 Another stabilizing factor is introduction of an electron withdrawing substi tuent into position 6 or 8 of indolizine. It turned out that when secondary amines are replaced by alkoxides, recyclization proceeds analogously (reac tion 26b, see Table 4) to give novel 5 alkoxyindoliz ines.24 The reaction did not occur with sterically hin dered high basicity nucleophiles (tert butoxide and di isopropylamine), as well as with phenoxides and second ary aromatic amines (probably because of their low nu cleophilicities). The scope of the recyclization we had discovered earli er were investigated in a study published in 2006.62 In that study, several interesting observations were cited. It turned out that the molar amount of secondary amine required

Scheme 26

for the reaction can be lowered by adding a tertiary amine. In addition, reaction 26a can be efficiently accelerated by microwave radiation. Finally, with an ambident reagent

Table 4. Synthesis of 5 substituted indolizines and their (cyclo)homologs R H H H H H H H H H H H H H H H (CH (CH (CH (CH H H H (CH2)3 (CH2)4 H H H H H H (CH2)3 NO2 H H H H (CH2)4
2)3 2)3 2)5 2)4

R´ H H H H H H H H H H H H H (CH2)4 (CH2)4

R H H H H H H H H H H Me Me Me

R´´´ H H H H H H H H H H H H H H H H H H H CN CONH2 CO2Et CONH2 CONH2 H H H H H H H

Ar p NO2C6H4 p NO2C6H4 p NO2C6H4 p NO2C6H4 p NO2C6H4 p NO2C6H4 p BrC6H4 p BrC6H4 3,4 Cl2C6H p ClC6H4 p NO2C6H4 p NO2C6H4 p NO2C6H4 p BrC6H4 p BrC6H4 p ClC6H4 p NO2C6H4 p ClC6H4 p ClC6H4 p BrC6H4 p BrC6H4 p BrC6H4 p ClC6H4 p ClC6H4 p ClC6H4 p NO2C6H4 p NO2C6H4 p NO2C6H4 p NO2C6H4 p BrC6H4 p NO2C6H4

HNR2 or OAlk Piperidine Hexamethylenimine Diethylamine Morpholine Pyrrolidine N Methylpiperazine Piperidine Morpholine Piperidine Piperidine Pyrrolidine Piperidine Hexamethylenimine Piperidine Morpholine Piperidine Morpholine Piperidine Piperidine Morpholine Morpholine Morpholine Piperidine Piperidine Morpholine MeO EtO PriO MeO MeO MeO

Yield (%) 66 65 37 79 60 74 71 38 88 89 45 83 63 60 25 98 40 97 72 56 41 35 87 67 65 66 43 63 39 79 62

References 21 61 23 60 23 23 23 23 23 23 25 25 25 25 25 28 28 27 27 23 23 23 34 35 17 24 24 24 24 24 28

3

H H H

Me Me Me Me Me Me Me H H Me H H H Me Me


Oxazolo[3,2 a]pyri(mi)dinium salts

Russ.Chem.Bull., Int.Ed., Vol. 57, No. 4, April, 2008

857

(4 aminopiperidine), it was found that the reaction in volves a more nucleophilic site (secondary N atom of the diamine). Note that we studied in detail the behavior in this recyclization of fused tricyclic salts 2 containing annulat ed alicyclic rings of different sizes.27,35 Such transforma tions are very uncommon since they are associated with a dramatic topological reconstruction of the tricycle: du ring the rearrangement, a linear structure is transformed into an angular one (Scheme 27) and an angular system is transformed into a peri fused tricycle (Scheme 28).
Scheme 27

Scheme 29

Scheme 28

Moreover, by varying the size of the alicyclic ring (Scheme 28), we determined the scope of the recycliza tion depending on nonevident steric factors, viz., the strain of the alicyclic ring annulated with the aromatic bi cycle.25,27,28 For a six or eight membered cycloalkane fragment, the recyclization proves to occur easily (Sche me 29, reactions 29a, 29b). For a seven membered alicy clic ring (reaction 29c), the reaction stops to yield stable intermediate 24a, which is less strained than aromatic system 24b. Finally, for a five membered alicyclic ring (reaction 29d), the oxazole ring seems to undergo opening; howev er, subsequent cyclization is impossible because the me thylene unit and the electrophilic site in intermediate 24c are distant from each other. An analogous effect was observed35 in tricyclic salts 2 containing an additional acceptor (an amide group in position 8). 4. Reactivity of oxazolopyrimidinium salts 4.1. Recyclization of the salts containing the 5 Me group As mentioned above, oxazolo[3,2 a]pyrimidinium salts 8a,b containing the 5 Me group are easiest to obtain (reaction 14a, Scheme 14). (The starting 2 aminoox azoles can be, in turn, easily prepared by condensation of cyanamide with accessible hydroxy ketones: acetoin or

benzoin.) Such salts are isostructural with the 5 Me ho mologs of oxazolopyridines and hence can be involved in the recyclization of the oxazole ring into a pyrrole one under the action of X type nucleophiles. We studied reactions of salts 8a,b with secondary amines and alkoxides. It turned out that tetramethyl salt 8a smoothly undergoes an earlier unknown recyclization to give the corresponding 1 amino or 1 alkoxypyrro lo[2,1 c]pyrimidines 25 (Scheme 30, Table 5).17,63 In analogous reactions of salts 8b, the yields were substan tially lower. The formation of pyrrolopyrimidines 25 is confirmed by mass spectra of the compounds obtained: in all cases,


858

Russ.Chem.Bull., Int.Ed., Vol. 57, No. 4, April, 2008

Babaev et al.

Table 5. Characteristics of pyrrolo[2,1 c]pyrimidines 25 Com pound 25a 25b 25c 25d 25e 25f 25g 25h
a b

the newly formed framework bonds (Scheme 31) shows that this strategy is very unusual.
m/z [M]+ Scheme 31 229 257 271 190 204 360 381 --

Substituents R Me Me Me Me Me Ph Ph Ph 1X N(CH2)4 N(CH2)6 N(CH2)7 Me OEt Me N(CH2)7 N(CH2)4

Yield (%)

M.p. /°

a

(4) (5) (s, 1 ) 5.91 5.92 5.92 5.87 5.85 6.49 6.33 6.38

40 65 48 73 80 7 13 2

6.50 6.52 b 6.52 30(2) 6.45 38(2) 6.42 128(1) 6.74 146(1) 6.72 137(2) 6.72
b

b

The 1H NMR spectrum (DMSO d6). Liquid. Scheme 30

the mass spectra contain a molecular ion peak and the molecular mass of the product equals the sum of the masses of the starting cation and anion of the nucleo phile (alkoxide or amide ion) minus the mass of a water molecule. In the 1H NMR spectra, a signal for the methyl group disappears (this signal was present in the spectrum of the starting cation) but a new aromatic singlet appears at 5.9 corresponding to the H(5) proton of the newly formed pyrrole ring. The resulting pyrrolopyrimidines, as well as indolizines, show a positive Ehrlich color probe; note that these pyrrolopyrimidines are more stable than analogous amino and alkoxyindolizines. The discovered reaction provides a novel strategy for the synthesis of the aromatic pyrrolo[2,1 c]pyrimidine system. In fact, we managed to effect a stepwise conver sion of 2 aminooxazoles into pyrrolo[1,2 c]pyrimidines through 5,7 dimethyloxazolopyrimidinium salts as in termediates. Consideration of the overall strategy of as sembly of this bicycle with regard to the reagents used and

Scheme 31 displays the reagents from which we "as sembled" the pyrrolo[1,2 c]pyrimidine system; particular emphasis should be given to the fact that these reagents are accessible and inexpensive. Seeking to understand the causes of the low yields in the recyclization of salts 8b, we varied the secondary amines and the reaction conditions. It turned out17 that reactions of the salt in boiling pure amine occur in an uncommon way (Scheme 32). A reaction of salt 8b with pyrrolidine (reaction 32a) gave only trace amounts of pyrrolopyrimidine 25h, while the major product was 2 amino 4,5 diphenyloxazole (26a). When salt 8b was refluxed in morpholine (reaction 32b), we unexpectedly isolated 2 morpholino 4,5 diphe nylimidazole (26b) as the sole product. To explain the observed facts, one should consider the structure of the plausible intermediate ylide 27 formed from salt 8b (see Scheme 32). Obviously, such an ylide is stabilized by additional delocalization of the negative charge over the phenyl ring; this stabilization is impossi ble in the ylides formed from salts 8a and 2. The stability of the ylide hinders cyclization of the pyrrole ring, which can be responsible for the noticeably lower yields of pyrrolopyrimidines from salt 8b (see Table 5). The formation of 2 aminooxazole 26a in reaction 32a with pyrrolidine can be explained only by opening (and complete decomposition) of the pyrimidine ring during this reaction. Therefore, two processes proceed in paral lel: opening of the oxazole ring gives pyrrolopyrimidine 25h and opening of the pyrimidine ring gives aminoox azole. Therefore, the bicyclic system of oxazolopyrimi dinium exhibits ambident properties in this reaction, which were not observed in other cases. The unexpected formation of aminoimidazole 26b (re action 32b) can be explained under the assumption that


Oxazolo[3,2 a]pyri(mi)dinium salts

Russ.Chem.Bull., Int.Ed., Vol. 57, No. 4, April, 2008

859

Scheme 32

the opening of the pyrimidine ring of salt 8b (as in reaction 32a of salt 8b with pyrrolidine) initially gives 2 aminooxazole, which under drastic conditions (reflux in amine) can further undergo recyclization into imid azole 26b. Similar examples of the oxazoleimidazole conversion have been documented (e.g., upon reflux of oxazoles with formamide).64 However, it turned out that oxazole is not a precursor of imidazole 26b (in a control experiment, oxazole remains intact upon reflux in mor pholine). The formation of the imidazole ring cannot be explained without plausible participation of intermedi ate ylide 27 (Scheme 33). Apparently, it is ylide 27 that reacts with the amine via stepwise decomposition of the pyrimidine ring and the formation of the guanidine fragment that undergoes cyclization into imidazole. In other words, the formation of aminoimidazole 26b can be explained under the as sumption that both rings in the bicyclic system undergo

opening and that a new cyclization involves a fragment of the resulting chain. Thus, two competitive processes proceed in parallel during reaction 32a: opening of both the oxazole and pyrimidine rings. The same processes are sequential in reaction 32b: the opening of the oxazole ring is followed by the opening of the pyrimidine one. In other words, the ambident nature of the oxazolopyrimidinium system is manifested in two different ways, which is very uncom mon in heterocyclic systems. When passing from X type to XH type nucleophiles, the oxazole ring in system 8a undergoes regioselec tive opening (Scheme 34).63 Reaction 34a with ammo nia gives imidazopyrimidine 28; its properties are iden tical with the literature data. Reaction 34b with an al kali c ould be expected (as with salts 2 by analogy with reaction 17a) to yield pyrimidone 29a. However, the final product is pyrrolopyrimidone 29b, probably

Scheme 33


860

Russ.Chem.Bull., Int.Ed., Vol. 57, No. 4, April, 2008

Babaev et al.

Scheme 34

because of the high acidity of the methyl group in inter mediate 29a. 4.2. Reactions of nucleophiles with 5 unsubstituted oxazolopyrimidinium salts Salt 9 (see Scheme 14, reaction 14b) reacts with vari ous XH and X type nucleophiles through opening of the pyrimidine ring.17 In reactions with morpholine, a pri mary aromatic amine, or hydrazine, salt 9 is transformed into 2 amino 4,5 dimethyloxazole (Scheme 35). (Re member that oxazolopyridine analogs 2 do not react with anilines at all, while their reactions with hydrazine in volve opening of the oxazole ring followed by recycliza tion (see Schemes 17 and 18).) In a reaction of salt 9 with p anisidine (reaction 35b), we isolated salt 30, which is a peculiar "fragment" of the opened pyrimidine ring. The structure of salt 30 was convincingly proved by 1H NMR spectroscopy (because of the molecular symmetry, the corresponding peaks of the protons show double in tensities). Note that even in a reaction with an alkali, no opening of the oxazole ring of salt 9 was detected, which was typical of oxazolopyridinium salts 2 and their 5 Me homologs. The 1H NMR spectrum of the unstable com pound obtained in the reaction of salt 9 with an alkali contained no signals characteristic of N substituted py
Scheme 35

rimidone and the product seemed to result from an attack of the hydroxide ion on the pyrimidine ring of the salt: an adduct or an open chain tautomer. Preparatively, a combination of Schemes 14 and 35 (transformation of oxazole into oxazolopyrimidine and the reverse conversion into the same oxazole) seems to hold no promise. Nevertheless, the transformations of oxazolopyrimidines into oxazoles make sense and are of practical value if one tries to synthesize an oxazolopyrim idinium salt from pyrimidine derivatives rather than from oxazoles. This would allow one to effect the interesting tandem sequence pyrimidines--oxazolopyrimidines--ox azole s as a novel promising strategy in heterocyclic chemistry. We reproduced one of few routes from pyrimidine to oxazolopyrimidinium salts according to Scheme 15 and obtained the desired representative 10 of this series (Ar = p ClC6H4). It turned out (Scheme 36)17,25 that this salt reacts with a secondary amine (reaction 36a) to give stable adduct 31 at the C(5) atom, which undergoes no further opening of the pyrimidine fragment.
Scheme 36

Morpholine

or

Compound Yield (%)

32a 12

32b 88 (with respect to salt 10)

32 80


Oxazolo[3,2 a]pyri(mi)dinium salts

Russ.Chem.Bull., Int.Ed., Vol. 57, No. 4, April, 2008

861

Hydrazinolysis of salt 10 (Scheme 36, reaction 36b) proceeded in a more complicated way to give a mixture of three compounds 32a--c. Along with the expected products (oxazole 32a and pyrazole 32b) resulting from the decomposition of the pyrimidine ring of salt 10, the reaction yielded triazine derivative 32c, probably via recyclization of the oxazole ring of salt 10 into triazine 33 followed by decomposition of its pyrimidine ring. Obviously, in this case too, the oxazolopyrimidine sys tem exhibit ambident properties: decomposition of the pyrimidine ring competes with opening (and recycliza tion) of the oxazole ring followed by the decomposition of the pyrimidine one. Thus, the synthesis of 2 aminooxazole (e.g., 32a) from pyrimidine through oxazolopyrimidinium salt 10 is fun damentally feasible; however, the overall reaction se quence consists of many steps, is labor consuming, and is complicated by a side process. We developed a novel, much simpler and more effi cient strategy of the synthesis of oxazole derivatives from pyrimidines through oxazolopyrimidinium salts. Above, we discussed the simple and convenient route from 2 pyr imidone to 2 aryloxazolopyrimidinium salts 12 (see Scheme 16, reactions 16a, 16c). It turned out17 that salts 12 react with secondary amines to give stable, bright ly colored azadienes (Scheme 37) (e.g., compound 34 characterized by X ray diffraction data).
Scheme 37

Table 6. Synthesis of oxazoles 35 Ar p ClC6H4 p BrC6H4 p NO2C6H4 Ph p CH3C6H4 Yield (%) 9 9 9 9 8 5 6 3 0 2 M.p./°C 220 221 236 215 218

Note that usually the current routes to 2 aminoox azoles either are complicated by side processes or consist of many steps involving complex reagents. The "text book" reactions of cyanamide with hydroxy carbonyl compounds are not suitable for the synthesis of 2 amino 5 aryloxazoles because hydroxyphenylacetaldehydes are not easily accessible. Thus, not only does the method proposed supplement successfully the current ones but it can also serve as their convenient alternative since it involves a straightforward sequence of high yield ing reactions of accessible and inexpensive starting ma terials. Recently,66 we have shown that the strategy under discussion (synthesis of 2 amino 1,3 azoles from pyrim idines through azolopyrimidinium salts) can be extend ed, e.g., to the synthesis of not easily accessible 2 ami noimidazoles from 2 aminopyrimidine derivatives. This work was financially supported by the Russian Foundation for Basic Research (Project No. 07 03 0092 a).

Morpholine

References
1. H. C. Van der Plas, Ring Transformation of Heterocycles, Aca demic Press, London, 1973, V. 1, 2. 2. E. V. Babaev, D. E. Lushnikov, N. S. Zefirov, J. Am. Chem. Soc., 1993, 115, 2416. 3. E. V. Babaev, N. S. Zefirov, Bull. Soc. Chim. Belg., 1992, 101, 67. 4. E. V. Babaev, N. S. Zefirov, Khim. Geterotsikl. Soedin., 1992, 808 [Chem. Heterocycl. Compd., 1992, 28, 658 (Engl. Transl.)]. 5. V. I. Terenin, E. V. Babaev, M. A. Yurovskaya, Yu. G. Bundel´, Khim. Geterotsikl. Soedin., 1992, 792 [Chem. Heterocycl. Compd., 1992, 28, 671 (Engl. Transl.)]. 6. D. A. Maiboroda, E. V. Babaev, Khim. Geterotsikl. Soedin., 1995, 1445 [Chem. Heterocycl. Compd., 1995, 31 , 1251 (Engl. Transl.)]. 7. E. V. Babaev, N. S. Zefirov, Khim. Geterotsikl. Soedin., 1996, 1564 [Chem. Heterocycl. Compd., 1996, 32, 1344 (Engl. Transl.)]. 8. C. K. Bradsher, M. F. Zinn, J. Heterocycl. Chem., 1964, 1, 219. 9. C. K. Bradsher, M. F. Zinn, J. Heterocycl. Chem., 1967, 4, 66. 10. C. K. Bradsher, R. D. Brandau, J. E. Boliek, T. L. Hough, J. Org. Chem., 1969, 34, 2129. 11. H. Pauls, F. KrÆhnke, Chem. Ber., 1976, 109, 3646. 12. D. G. Kim, G. G. Skvortsova, Khim. Geterotsikl. Soedin., 1986, 1396 [Chem. Heterocycl. Compd., 1986, 21 (Engl. Transl.)]. 13. R. H. Good, G. Jones, J. Chem. Soc. C, 1970, 1938.

Hydrazinolysis of salts 12 (Scheme 38) gives 2 ami no 5 aryloxazoles 35 in high yields (Table 6).46 The con stants of the oxazoles (melting points, 1H NMR spectra) are identical with the literature data. We also recorded their 13C NMR and mass spectra missing in the litera ture; the structure of one of the compounds was con firmed by X ray diffraction analysis.65
Scheme 38


862

Russ.Chem.Bull., Int.Ed., Vol. 57, No. 4, April, 2008

Babaev et al.

14. E. V. Babaev, V. B. Rybakov, I. A. Orlova, A. A. Bush, K. V. Maerle, A. F. Nasonov, Izv. Akad. Nauk, Ser. Khim., 2004, 170 [Russ. Chem. Bull., Int. Ed., 2004, 53, 176]. 15. E. V. Babaev, A. F. Nasonov, ARKIVOC, 2001, 2, 139. 16. A. A. Bush, Ph.D. (Chem.) Thesis, Moscow State University, Moscow, 2006, 140 pp. 17. E. V. Babaev, D.Sc. (Chem.) Thesis, Moscow State University, Moscow, 2008, 450 pp. 18. I Li Chen, Yeh Long Chen, Tai Chi Wang, Cherng Chyi Tzeng, Heterocycles, 2003, 60, 131. 19. D. A. Maiboroda, E. V. Babaev, L. V. Goncharenko, Khim. Farm. Zh., 1998, 32, 6, 24 [Pharm. Chem. J., 1998, 32, 310 (Engl. Transl.)]. 20. D. A. Maiboroda, Ph.D. (Chem.) Thesis, Moscow State Uni versity, Moscow, 1998, 165 pp. 21. E. V. Babaev, A. V. Efimov, D. A. Maiboroda, K. Jug, Eur. J. Org. Chem., 1998, 193. 22. E. V. Babaev, A. V. Efimov, D. A. Maiboroda, Khim. Geterotsikl. Soedin., 1995, 1104 [Chem. Heterocycl. Compd., 1995, 31, 962 (Engl. Transl.)]. 23. A. V. Efimov, Ph.D. (Chem.) Thesis, Moscow State University, Moscow, 2006, 137 pp. 24. E. V. Babaev, A. V. Efimov, A. A. Tsisevich, A. A. Nevskaya, V. B. Rybakov, Mendeleev Commun., 2007, 17, 130. 25. A. A. Tsisevich, Ph.D. (Chem.) Thesis, Moscow State Universi ty, Moscow, 2006, 129 pp. 26. D. V. Albov, V. B. Rybakov, E. V. Babaev, L. A. Aslanov, Acta Cryst., Section E, 2004, E60, o2313. 27. D. V. Albov, Ph.D. (Chem.) Thesis, Moscow State University, Moscow, 2005, 140 pp. 28. E. V. Babaev, A. A. Tsisevich, D. V. Albov, V. B. Rybakov, L. A. Aslanov, Izv. Akad. Nauk, Ser. Khim., 2005, 253 [Russ. Chem. Bull., Int. Ed., 2005, 54, 259]. 29. D. V. Albov, V. B. Rybakov, E. V. Babaev, L. A. Aslanov, Kristallografiya, 2004, 49, 495 [Crystallogr. Reprts, 2004, 49, 430 (Engl. Transl.)]. 30. D. V. Albov, V. B. Rybakov, E. V. Babaev, L. A. Aslanov, Acta Cryst., Section E, 2004, E60, o1096. 31. D. V. Albov, V. B. Rybakov, E. V. Babaev, L. A. Aslanov, Acta Cryst., Section E, 2004, E60, o1301. 32. D. V. Albov, E. I. Turubanova, V. B. Rybakov, E. V. Babaev, L. A. Aslanov, Acta Cryst., Section E, 2004, E60, o1303. 33. O. S. Mazina, V. B. Rybakov, S. I. Troyanov, E. V. Babaev, L. A. Aslanov, Kristallografiya, 2005, 50, 68 [Crystallogr. Reprts, 2005, 50, 61 (Engl. Transl.)]. 34. O. S. Mazina, V. B. Rybakov, V. V. Chernyshev, E. V. Babaev, L. A. Aslanov, Kristallografiya, 2004, 49, 1095 [Crystallogr. Reprts, 2004, 49, 998 (Engl. Transl.)]. 35. O. S. Mazina, Ph.D. (Chem.) Thesis, Moscow State University, Moscow, 2005, 150 pp. 36. A. A. Bush, E. V. Babaev, Molecules, 2003, 8, 460; http:// www.mdpi.org/molecules/papers/80600460.pdf 37. Z. G. M. Kazhkenov, A. A. Bush, E. V. Babaev, Molecules, 2005, 10, 1109; http://www.mdpi.org/molecules/papers/ 10091109.pdf. 38. E. V. Babaev, N. I. Vasilevich, A. S. Ivushkina, Beilstein J. Org. Chem., 2005, 1, 9; http://bjoc.beilstein journals.org/content/ pdf/1860 5397 1 9.pdf. 39. E. V. Babaev, I. A. Orlova, Khim. Geterotsikl. Soedin., 1997, 569 [Chem. Heterocycl. Compd., 1997, 33, 489 (Engl. Transl.)].

40. E. V. Babaev, J. Heterocycl. Chem., 2000, 37, 519. 41. V. A. Chuiguk, E. A. Leshchenko, Ukr. Khim. Zh. [Ukrainian Journal of Chemistry], 1974, 40, 633 [Chem. Abstr., 1974, 81, 105438]. 42. S. I. Shul´ga, V. A. Chuiguk, Ukr. Khim. Zh. [Ukrainian Journal of Chemistry], 1972, 38, 169 (in Russian). 43. S. I. Shul´ga, V. A. Chuiguk, Ukr. Khim. Zh. [Ukrainian Journal of Chemistry], 1970, 36, 483 (in Russian). 44. J. Liebscher, A. Hassoun, Synthesis, 1988, 816. 45. B. Reimer, M. Patzel, A. Hassoun, J. Liebscher, Tetrahedron, 1993, 49, 3767. 46. V. L. Alifanov, E. V. Babaev, Synthesis, 2007, 263. 47. V. B. Rybakov, V. L. Alifanov, P. V. Gormay, E. V. Babaev, Acta Cryst., Section E, 2006, E62, o3840. 48. V. B. Rybakov, V. L. Alifanov, E. V. Babaev, Acta Cryst., Section E, 2006, E62, o4578. 49. E. V. Babaev, V. B. Rybakov, S. G. Zhukov, I. A. Orlova, Khim. Geterotsikl. Soedin., 1999, 542 [Chem. Heterocycl. Compd., 1999, 35, 479 (Engl. Transl.)]. 50. D. A. Maiboroda, E. V. Babaev, K. Jug, J. Org. Chem., 1997, 62, 7100. 51. E. V. Babaev, K. Yu. Pasichnichenko, D. A. Maiboroda, Khim. Geterotsikl. Soedin., 1997, 397 [Chem. Heterocycl. Compd., 1997, 33, 338 (Engl. Transl.)]. 52. A. R. Katritzky, A. Zia, J. Chem. Soc., Perkin Trans. 1, 1982, 131. 53. G. Markl, S. Pflaum, Tetrahedron Lett., 1987, 28, 1511. 54. E. V. Babaev, A. V. Efimov, V. B. Rybakov, S. G. Zhukov, Khim. Geterotsikl. Soedin., 1999, 550 [Chem. Heterocycl. Compd., 1999, 35, 488 (Engl. Transl.)]. 55. E. V. Babaev, S. V. Bozhenko, D. A. Maiboroda, Izv. Akad. Nauk, Ser. Khim., 1995, 2298 [Russ. Chem. Bull., Int. Ed., 1995, 44, 2203]. 56. E. V. Babaev, S. V. Bozhenko, Khim. Geterotsikl. Soedin., 1997, 141 [Chem. Heterocycl. Compd., 1997, 33, 125 (Engl. Transl.)]. 57. E. V. Babaev, A. V. Efimov, V. B. Rybakov, S. G. Zhukov, Khim. Geterotsikl. Soedin., 2000, 401 [Chem. Heterocycl. Compd., 2000, 36, 339 (Engl. Transl.)]. 58. E. V. Babaev, S. V. Bozhenko, D. A. Maiboroda, V. B. Rybakov, S. G. Zhukov, Bull. Soc. Chim. Belg., 1997, 106, 631. 59. V. B. Rybakov, E. V. Babaev, A. A. Tsisevich, A. V. Arakcheeva, A. Shonleber, Kristallografiya, 2002, 47, 1042 [Crystallogr. Reprts, 2002, 47, 973 (Engl. Transl.)]. 60. E. V. Babaev, A. V. Efimov, Khim. Geterotsikl. Soedin., 1997, 998 [Chem. Heterocycl. Compd., 1997, 33, 964 (Engl. Transl.)]. 61. E. V. Babaev, A. V. Efimov, S. G. Zhukov, V. B. Rybakov, Khim. Geterotsikl. Soedin., 1998, 852 [Chem. Heterocycl. Compd., 1998, 34, 852 (Engl. Transl.)]. 62. P. Tielmann, C. Hoenke, Tetrahedron Lett., 2006, 47, 261. 63. E. V. Babaev, V. L. Alifanov, Izv. Akad. Nauk, Ser. Khim., 2007, 1611 [Russ. Chem. Bull., Int. Ed., 2007, 56, 1675]. 64. R. Gompper, O. Christmann, Chem. Ber., 1959, 92, 1945. 65. V. B. Rybakov, V. L. Alifanov, E. V. Babaev, Acta Cryst., Section E, 2006, E62, o4809. 66. D. S. Ermolat´ev, E. V. Babaev, E. V. Van der Eycken, Org. Lett., 2006, 8, 5781.

Received January 28, 2008