Photochemistry of bicyclo[2.2.2]oct-7-ene-2,5-diones and the corresponding 5-hydroxyimino and 5-methylene derivatives

Synthesis and photochemistry of several title compounds 1-3 containing multiple chromophoric systems are described. The Diels-Alder reactions of 2,6,6-trimethylcyclohexa-2,4-dienone (5) with acetylenes 6a-d provided the adducts 7a-d, which upon hydrolysis furnished the desired bicyclo[2.2.2]octenediones 1a-d. Oximes 2a-d were prepared from diones 1a-d by treatment with hydroxylamine hydrochloride in pyridine. 5-Methylenebicyclo[2.2.2]oct-7-en-2-ones 3a-d were obtained via chemoselective Wittig reaction of the corresponding diones 1a-d. Bicyclo[2.2.2]octenediones 1a-c underwent chemoselective oxa-di-pi-methane rearrangement under sensitized conditions and suffered formal ketene extrusion upon direct irradiation. Direct irradiation of 1d afforded 11d via formal ketene extrusion but under sensitization it remained unchanged. Oximes 2a-d suffered ketene extrusion upon direct irradiation and E/Z isomerization under sensitized conditions. On the other hand, 5-methylenebicyclo[2.2.2]oct-7-en-2-ones 3a-d generally underwent 1,3-acyl shift. The plausible courses of all these photochemical processes are discussed.     

A Convenient Preparation of 2-(2-Arylidene)- and 2-(2-Polyhydroxyalkylidene)hydrazono-4-imidazolidinones with Various Heterocyclic Side Chain Substituents at Position 5 as Potential Antiviral and Antitumor Agents

A variety of novel 5-[( Z )-arylidene]-2-[(2-( E )-arylidene)hydrazono]-4-imidazolidinones 1a-c to 4a , b and 5-[( Z )-arylidene]-2-[(2-( E )-polyhydroxyalkylidene)hydrazono]-4-imidazolidinones 5a-c to 7a-c were prepared from the reaction of 5-[( Z )-arylidene]-2-methylmercaptohydantoins 8a-c with 2-( E )-arylidene hydrazones 13a-d and/or 2-( E )-monosaccharides hydrazones 16a-c . The linear structure, and not that of the angular isomer, has been selected for the products. This structure has been confirmed from a model study of the condensation of 5-[( Z )-2-thienylidene]-2-hydrazono-4-imidazolidinone 9a with benzaldehyde and D -galactose, respectively. The acetylation and benzoylation reactions of compounds 1-7 have been studied. All the new compounds were tested for their potential antiviral and antitumor activities.     

NaOH-catalyzed thiolysis of alpha,beta-epoxyketones in water. A key step in the synthesis of target molecules starting from alpha,beta-unsaturated ketones

NaOH (0.02-0.3 molar equiv) is an efficient catalyst for the thiolysis reactions of alpha,beta-epoxy ketones with alkyl and aryl thiols in water. Thiolysis of 3,4-epoxyheptan-2-one (1) with thiols 2a-d has been accomplished in mild conditions (30 degrees C and pH 6 or 9) with complete C-alpha-regioselectivity and anti-stereoselectivity, and the corresponding anti-beta-carbonyl-beta-hydroxysulfides 3a-d have been prepared in excellent yields (95-98%). Compounds 3a-d, depending on their nature and pH conditions, have undergone dehydration, C-3 epimerization reaction, and retroaldol condensation. Dehydration of anti-3a-d has been chemoselectively carried out by in situ acidic treatment at 70 degrees C, giving stereoselectively the related (Z)-vinyl sulfides 4 in 89-94% overall yields. Under NaOH-catalyzed thiolysis conditions, cyclic alpha,beta-epoxyketones 6-9 have shown C-alpha attack only and spontaneously dehydrated to furnish the corresponding vinyl sulfides in high yields (90-96%). The reactions of calchone oxide (10) with thiols 2b-d have exclusively resulted in the formation of beta-carbonylsulfides 10b-d (82-93% yield), coming from the nucleophilic attack at the alpha-position and retroaldol condensation. To highlight the synthetic utility of this procedure, one-pot multisteps preparation of vinyl sulfides 7b and 7c, vinyl sulfoxides 12 and 13, and 1,5,6,7-tetrahydro-4H-1,2,3-benzotriazol-4-one (14) starting from 2-cyclohexen-1-one (11) have also been reported.     

Photolytic, thermal, addition, and cycloaddition reactions of 2-diazo-5,6- and -3,8-disubstituted acenaphthenones

Preparation and varied thermal and photolytic reactions of 2-diazo-5,6-(disubstituted)acenaphthenones (11a-d) and 2-diazo-3,8-dimethoxyacenaphthenone (12) are reported. Alcohols react thermally and photolytically with 11a-c with losses of N(2) to yield 2-alkoxynaphthenones (24a,band 47a,b) and acenaphthenones (25 and 48a,b). Aniline and diphenylamine are converted by 11a-c at 180 degrees C to acenaph[1,2-b]indoles (29a,b and 53a,b). Thermolyses of 11a-c at approximately 450 degrees C (0.15 mmHg) yield reduction products 25 and 48a,b, respectively. Wolff rearrangements to 1,8-naphthyleneketenes (15a-d) and/or their derivatives are not observed in the above experiments. Oxygen converts 11a-c thermally to acenaphthenequinones (19a-c) and/or 1,8-naphthalic anhydrides. Insertion, addition, substitution, and/or isomerization reactions occur upon irradiation of 2-diazoacenaphthenones in cyclohexane, benzene, and tetrahydrofuran. Photolysis of 11d in benzene in the presence of O(2) yields the insertion-oxidation product 2-hydroxy-5,6-dinitro-2-phenylacenaphthenone (60). Photolyses of 11a-c in nitriles result in N(2) evolution and dipolar cycloaddition to give acenaph[1,2-d]oxazoles (41 and 61a,b). Acetylenes undergo thermal and photolytic cycloaddition/1,5-sigmatropic rearrangement reactions with 11a-d with N(2) retention to give pyrazolo[5,1-a]quinolin-7-ones (69f-j). 2-Diazoacenaphthenones 1a and 11a react thermally and photolytically with electronegatively-substituted olefins with N(2) expulsion to yield (E)- and (Z)-2-oxospiro[acenaphthylene-1(2H),1'cyclopropanes] 73a-c and 74a-c, respectively. The mechanisms of the reactions of 1a, 11a-d, and 12 reported are discussed.     

First synthesis and isolation of the E- and Z-isomers of some new Schiff bases. Reactions of 6-azido-5-formyl-2-pyridone with aromatic amines

Some novel Schiff bases have been prepared by reacting 6-azido-5-formyl-2-pyridone 1 with a series of aromatic amines 2a-f. 5-Arylaminomethylene-6-(E)-aryl-iminopyridones 3a-e were obtained by reaction of 1 with 2a-e at room temperature, whereas with 2f, the 6-azido-5-naphthalen-2-yl-iminomethylpyridone derivative 4 was formed. On the other hand, heating 1 with 2a-d at 140-150 degrees C yielded two sets of isomeric products, (E)-3a-d and (Z)-5a-d. Refluxing compounds (Z)-3a,c with hydroxyl-amine in methanol gave the corresponding hydroxyliminopyridones 8a,c. Heating of (E)-3a-d with excess POCl3 at reflux did not give the expected tricyclic compound 9, but rather the isomeric products (Z)-5a-d were obtained. The structures of all these products have been characterized using IR and 1H- and 13C-NMR spectroscopy.     

Tandem transesterification and intramolecular cycloaddition of alpha-methoxycarbonylnitrones with chiral acyclic allyl alcohols: systematic studies on the factors affecting diastereofacial selectivity of the cycloaddition

Factors affecting the stereochemical course of the intramolecular cycloaddition of intermediary alpha-allyloxycarbonylnitrone resulting from transesterification of alpha-methoxycarbonylnitrones 1a-d with chiral allyl alcohols 5 or 6 were investigated systematically. It was found that the factors of diastereofacial selection are highly dependent on the geometries of the allyl alcohols. In the cases where primary or secondary chiral (Z)-allyl alcohols are used, A(1,3)-strain arising from the chiralities in the (Z)-nitrone transition states of the intramolecular cycloaddtion is the most important factor. In contrast, in the case of the reaction using chiral nitrones 1c,d and (E)-allyl alcohols, steric interaction between the chiral N-substituent and the trans substituent of the olefin moiety in the intermediate is dominant. These aspects were applied to geometry-differentiated cycloaddition using a mixture of (E)-5 and (Z)-5. As a typical example, treatment of bulky 1b with a 1:1 mixture of (E)-5 and (Z)-5 in the presence of a catalytic amount of TiCl(4) and MS 4A gave 7b as the predominant product among four possible products.     

Peri- and enantioselectivity of thermal, scandium-, and [pybox/scandium]-catalyzed Diels-Alder and hetero-Diels-Alder reactions of methyl (E)-2-oxo-4-aryl-butenoates with cyclopentadiene

The cycloaddition between methyl (E)-2-oxo-4-aryl-3-butenoates (2 a-d) and cyclopentadiene, in addition to the expected normal Diels-Alder (DA) adducts endo-3 a-d and exo-4 a-d, gives the less expected endo-5 a-d products of the [4+2] hetero-Diels-Alder (HDA) reaction in which the alpha-ketoester behaves as a heterodiene. If a comparison is made between the thermal and the scandium(III) triflate-catalyzed conditions, the periselectivity changes and whereas under thermal conditions the main products are those from the DA reaction (3 a-d), in the presence of Sc(OTf)3 (OTf=triflate), the HDA products 5 a-d become largely predominant. The reactions are enantioselectively catalyzed by the scandium(III) triflate complex of (4'S,5'S)-2,6-bis[4'-(triisopropylsilyl)oxymethyl-5'-phenyl-1',3'-oxazolin-2'-yl]pyridine (1) and both the DA and the HDA products are obtained with excellent enantiomeric excess, up to >99% ee. The X-ray crystallographic structure determination of 5 c assigns it the 4R,4aS,7aR absolute configuration. The thermal retro-Claisen rearrangement of 3 c into (4R,4aS,7aR)-5 c allows the correlation of their absolute configuration, and 3 c has therefore the 2R,3R configuration. By analogy the same absolute configuration can be assigned to 3 a,b,d and 5 a,b,d, and the stereospecific thermal Claisen rearrangement of the optically active 5 a,b,d into 3 a,b,d completes the correlation between their absolute configuration. The [3,3]-sigmatropic rearrangements can be easily carried out under catalytic conditions with scandium(III) triflate, which promotes the equilibration between 3 a-d and 5 a-d, with a different degree of enantioselectivity characterizing the process starting from 3 a-d or 5 a-d. The unambiguous attributions of the configuration to the products allows us to propose a rationale of the stereochemical outcome of the catalyzed cycloaddition and to investigate the reaction mechanism of the competing DA and HDA reactions and shifts in products distribution by acid catalysis.     

Methylene-bridged glycoluril dimers: synthetic methods

Methylene-bridged glycoluril dimers are the fundamental building blocks of cucurbituril (CB[6]), its homologues (CB[n]), and its derivatives. This paper describes three complementary methods for the synthesis of C- and S-shaped methylene-bridged glycoluril dimers (29-34 and 37-44). For this purpose, we prepared glycoluril derivatives (1a-d) bearing diverse functionalities on their convex face. These glycoluril derivatives were alkylated under basic conditions (DMSO, t-BuOK) with 1,2-bis(halomethyl)aromatics 6-15 to yield 4a-d and 16-24, which contain a single aromatic o-xylylene ring and potentially nucleophilic ureidyl NH groups. Glycoluril derivatives bearing potentially electrophilic cyclic ether groups (5a-f) and 25-28 were prepared by various methods including condensation reactions in refluxing TFA containing paraformaldehyde. The condensation reactions of 4a-d and 16-24 with paraformaldehyde under anhydrous acidic conditions (PTSA, ClCH(2)CH(2)Cl, reflux) give, in most cases, the C-shaped and S-shaped methylene-bridged glycoluril in good to excellent yields. In many cases, the C-shaped compound is formed preferentially with high diastereoselectivity. Cyclic ethers 5a,d-f and 25-26 undergo highly diastereoselective dimerization reactions to yield methylene-bridged glycoluril dimers with the formal extrusion of formaldehyde. Last, it is possible to perform selective heterodimerization reactions using both cyclic ethers and glycoluril derivatives bearing ureidyl NH groups. These reactions deliver the desired C- and S-shaped heterodimers with low to moderate diastereoselectivities. This heterodimerization route is the method of choice in cases where the homodimerization reactions fail. The formation of side products (+/-)-35b and (+/-)-35d helps clarify the electronic requirements for a successful CB[n] synthesis. The X-ray structures of 30C, 38C, and 38S allow for a discussion of the structural features of this class of compounds.     

Synthesis of new imidazo[4,5-d][1,3]diazepine derivatives from 5-amino-4-(cyanoformimidoyl)imidazoles

N¹-[(Z) -2- Amino-1,2-dicyanovinyl]formamidines 1a-d react readily with tosyl isocyanate to form novel 8-amino-3-substituted-5-oxo-7-tosylaminoimidazo[4,5-d][1,3]diazepines 6a-d rather than the 6-cyano-2-oxopurine derivatives 5a-d expected. Compound 5a has been synthesized from 1a by reaction with ethyl chloroformate and base-catalyzed cyclization of the resultant 5-ethoxycarbonylamino-4-(cyanoformimidoyl)imidazole. Treatment of the 5-amino-4-cyanoimidazoles 7a and b with tosyl isocyanate under similar conditions gives the 4-cyano-5-(3′-tosylureido)imidazoles 8a and b , which on treatment with ethanolic ammonia cyclizes to the corresponding isoguanines 10a and b .     

Reactivity of p-phenyl substituted β-enamino compounds using K-10/ultrasound. I. Synthesis of pyrazoles and pyrazolinones

The reactivity of the β-enamino ketones, 3-amino-1-(p-phenyl-substituted)-2-buten-1-ones 1a-d and β-enamino esters, ethyl 3-amino-3-(p-phenyl-substituted)-2-propenoates 5a-d was systematically studied when allowed to react with hydrazine and methylhydrazine under solid support K -10/ultrasound conditions and in homogeneous media (reflux in ethanol or dichloromethane). The products were pyrazoles 2a-d , N-methylpyrazoles 3a-d, 4a-d and N-methylpyrazolinones 6a-c and 7a-c . The regiochemistry of the cyclization reactions showed dependence upon the reaction conditions employed as well as upon the sub-stituent in the aromatic ring.     

Reactivity of p-phenyl substituted β-enamino compounds using k-10/ultrasound. I. synthesis of pyrazoles and pyrazolinones

The reactivity of the β-enamino ketones, 3-amino-1-(p-phenyl-substituted)-2-buten-1-ones 1a-d and β-enamino esters. Ethyl-3-amino-3-(p-phenyl-substituted)-2-propenoates 5a-d were evaluated by systematic studies of the reactions with hydrazine and methylhydrazine by reactions with solid support K-10/ultrasound and homogeneous media (reflux in ethanol or dichloromethane) yielding pyrazole rings 2a-d , N-methylpyrazoles 3a-d, 4a-d and N-methylpyrazolinones 6a-c and 7a-c . The regiochemistry of the cyclization showed dependence of the reaction conditions employed as well as the substituent in the aromatic ring.     

Nucleophilic di- and tetrafluorination of dicarbonyl compounds

Reactions of various diketo compounds with Deoxofluor [(CH(3)OCH(2)CH(2))(2)NSF(3)] have been investigated. When reacted with Deoxofluor, alpha-diketones, R(1)COCOR(2) (R(1) = R(2) = Ph; R(1) = R(2) = 4-Me-C(6)H(4); R(1) = Ph, R(2) = Me; R(1) = Me, R(2) = Et) (1a-d) formed difluoro derivatives (2a-d) in the presence of a catalytic amount of HF and/or tetrafluoro (3a-d) products depending on the reaction conditions and stoichiometry used. Reactions of beta-diketones, R(3)COCH(2)COR(4) (R(3) = R(4) = Ph; R(3) = R(4) = Me; R(3) = Me, R(4) = Ph) (4e-g), with Deoxofluor in the presence of a catalytic amount of HF led to the formation of difluoroalkenones as a mixture of E (5e-g) and Z (6e-g) isomers in good yield. Reaction of other diones, R(5)CO-X-COR(6) (R(5) = R(6) = Ph, X = -CH=CH-; R(5) = R(6) = Me, X = -C(6)H(4)C(6)H(4)-; R(5) = R(6) = Ph, X = -CH(2)CH(2)CH(2)-; R(5) = R(6) = Me, X = -CH(2)CH(2)-) (7h-k) with Deoxofluor produced mainly difluoro products (8h-k) with low yields of tertrafluoro derivatives (9h-k). Acyclic alpha-keto amides react poorly to give the corresponding difluoro derivatives, whereas cyclic alpha-keto amides (10l-p) react smoothly under very mild conditions to produce the corresponding difluoro products (11l-p) in >88% isolated yield.     

Nucleosides and Nucleotides. 151. Conversion of (Z)-2'-(Cyanomethylene)-2'-deoxyuridines into Their (E)-Isomers via Addition of Thiophenol to the Cyanomethylene Moiety Followed by Oxidative Syn-elimination Reactions(1)

The Wittig reaction of 1-[3,5-O-(1,1,3,3-tetraisopropyldisiloxane-1,3-diyl)-beta-D-erythro-pentofuranos-2-ulosyl]uracil (6) with Ph(3)P=CHCN afforded (Z)-2'-cyanomethylene derivative 7 exclusively. The (E)-isomer was accessed from its (Z)-isomer through a sequence of addition of thiophenol to the 2'-cyanomethylene moiety of the (Z)-isomer from the alpha-face, selectively, and stereoselective oxidative syn-elimination of the resulting adduct. The diastereofacial selectivity of the benzenethiolate addition to the cyanomethylene moiety was found to be influenced by participation of the 2-carbonyl group at the base moiety and steric hindrance of the sugar protecting groups. Although nucleophilic addition reactions at the 2'-position of 6 have been well-known to occur from the alpha-face selectively, treatment of 7 with LiSPh in THF unexpectedly afforded a mixture of alpha- and beta-phenylthio derivatives 8 and 9 in almost equal ratio. Furthermore, an unusual beta-facial selective addition was observed on treatments of 7 with PhSAlMe(2) in CH(2)Cl(2) or with LiSPh in the presence of Mg(ClO(4))(2) in THF. On the other hand, when (Z)-2'-(cyanomethylene)-5'-O-triisopropylsilyl derivative 10 was treated with LiSPh, the alpha-phenylthio derivative 13 was obtained predominantly (89:11). Oxidation of 8 with m-chloroperbenzoic acid (m-CPBA) in CH(2)Cl(2) and pyrolysis of the resulting sulfoxides afforded the (Z)-isomer 7 exclusively. Treatment of 13 with m-CPBA under the same conditions afforded the desired (E)-cyanomethylene derivatives 18 as a major product (E:Z = 14:1) in good yield. Deprotection of 18 by the standard procedures furnished (E)-2'-(cyanomethylene)-2'-deoxyuridine (5).     

Intramolecular Diels-Alder reactions of brominated masked o-benzoquinones. A detour method to synthesize highly functionalized oxatricyclic [m.3.1.0] ring systems from 2-methoxyphenols

Intramolecular Diels-Alder (IMDA) reactions of masked o-benzoquinones (MOBs) 5a-d to 7a-d and 17a-d to 19a-d generated in situ from 2-methoxyphenols 2-4 and 14-16, respectively, in the presence of alkenols 1a-d, resulting in highly functionalized oxatricyclic [m.3.1.0] ring systems are described. The MOBs 5a-d to 7a-d underwent the IMDA reactions to furnish the adducts 8a-d, 10a-d, and 12a-d (direct method) in poor yields with the concomitant formation of considerable amounts of unexpected byproducts 9a-d, 11a-d, and 13a-d, respectively. To avoid the formation of byproducts and to improve the yields of the desired cycloadducts, a detour method comprising sequential bromination of 2-methoxyphenols 2-4, tandem oxidative acetalization-Diels-Alder reaction, and debromination has been developed. The oxidation of bromophenols 14-16 in the presence of alkenols 1a-d produced the corresponding MOBs 17a-d to 19a-d, which underwent cycloaddition to afford the cycloadducts 20a-d to 22a-d, respectively, as sole products in good to high yields in a highly regio- and stereoselective manner. Treatment of the bromoadducts 20a-d to 22a-d with tributylammonium formate-palladium reagent produced the corresponding debrominated products 8a-d, 10a-d, and 12a-d in high to excellent yields. In general, the latter oxatricycles were obtained in higher overall yields via the detour method than those via the direct method.     

Synthesis of 2-(3-tropolonyl)-1-benzopyrylium perchlorates and related compounds

3-Acetyltropolone ( 1 ) reacted with 2-hydroxybenzaldehyde ( 3a ) in the presence of perchloric acid in ethyl orthoformate to afford 2-(3-tropolonyl)-1-benzopyrylium perchlorate ( 4a ). The reactions with 2-hydroxy-5-methylbenzaldehyde ( 3b ), 5-chloro-2-hydroxybenzaldehyde ( 3c ), and 2-hydroxy-1-naphthalde-hyde ( 3d ) gave respectively the corresponding products 4b-d . The reactions of 2-acetyl-7-methylamino-tropone ( 2 ) with 3a-d also gave the corresponding products 5a-d , respectively.     

Chemistry of the enaminone of 1-acetylnaphthalene under microwave irradiation using chitosan as a green catalyst

Enaminone 1 was reacted with hydrazonoyl halides 2a-d to yield 3,4-disubstituted pyrazoles 6a-d. Coupling with arenediazonium chlorides afforded the 2-(arylhydrazono)-3-(1-naphthalenyl)-3-oxopropionaldehydes 13a-c. Compounds 13 could be utilized for the synthesis of a variety of arylpyrazoles, arylazolopyrimidines, and pyridazinones via reaction with hydrazines, aminoazoles, and active methylene derivatives, respectively. A comparative study of aforementioned reactions was carried out with chitosan as a basic ecofriendly catalyst under conventional heating as well as under pressurized microwave irradiation conditions.     

Nucleophilic reactivities of benzenesulfonyl-substituted carbanions

Kinetics of the reactions of four benzenesulfonyl-stabilized carbanions (1a-d)- with reference electrophiles (quinone methides 2 and diarylcarbenium ions 3) have been determined in dimethyl sulfoxide solution at 20 degrees C in order to derive the reactivity parameters N and s according to the linear free-energy relationship logk(20 degrees C) = s(N + E) (eqn (1)). The additions of (1a-d)- to ordinary Michael acceptors (e.g., benzylidene Meldrum's acid 4a, benzylidenebarbituric acids 5a-c, and benzylidene-indan-1,3-diones 6a-d) were also studied kinetically and found to be 5-24 times slower than predicted by eqn (1).     

Crystalline-state Z,E-photoisomerization of a series of (Z,E,Z)-1,6-diphenylhexa-1,3,5-triene 4,4'-dicarboxylic acid dialkyl esters. Chain length effects on the crystal structure and photoreactivity

[reaction: see text] Crystalline-state Z,E-photoisomerization of a series of (Z,E,Z)-1,6-diphenylhexa-1,3,5-triene 4,4'-dicarboxylic acid dialkyl (R) esters [(Z,E,Z)-1a, R = Me; (Z,E,Z)-1b, R = Et; (Z,E,Z)-1c, R = n-Pr; (Z,E,Z)-1d, R = n-Bu] was investigated. All Z,E,Z isomers underwent one-way isomerization to the corresponding E,E,E isomers. The reaction efficiency was strongly enhanced as the length of the alkyl chain increased. Single-crystal X-ray analyses of (Z,E,Z)-1a-d showed that the alkyl chain part of the crystals became larger as the chain length increased. The conformational flexibility of the alkyl chains made the large change in the triene geometry in the lattice possible, leading to the enhancement of the photoreactivity in the crystalline state.     

Lithiation of 1-chloromethylbenzotriazole: generation and elaboration of benzotriazolyloxiranes

1-Benzotriazolylchloromethyllithium generated from 1-chloromethylbenzotriazole (1) and LDA reacts with enolizable and nonenolizable ketones to give benzotriazolyloxiranes 2a-g in good yields. The oxiranyllithiums 4a-d generated from 2a-d and n-BuLi at -78 degrees C were trapped by a variety of electrophiles to give oxiranyl derivatives 5a-j in good to excellent yields. Lewis-acid-promoted nucleophilic ring opening of benzotriazolyloxiranes 2a,f,g with allyltrimethylsilane gave the corresponding 1,7-octadien-4-ols 6a-c in 68-75% yield. Hydrolysis of alpha-acylbenzotriazolyloxiranes 5g,h provided 3-hydroxy-1,2-diones 7a and 7b in 73 and 86% yield, respectively.     

Syntheses of optically active tetrahydro-1H-pyrrolo[1,2-a]imidazol-2-ones and hexahydroimidazo[1,2-a]pyridin-2(3H)-ones

The reactions of (2S)-2-amino-2-substituted-N-(4-nitrophenyl)acetamides 16a-c, succindialdehyde (13), and benzotriazole afforded enantiopure (3S,5R,7aR)-5-(1H-1,2,3-benzotriazol-1-yl)-3-substituted-1-(4-nitrophenyl)tetrahydro-1H-pyrrolo[1,2-a]imidazol-2-ones 17a-c, which were converted by sodium borohydride into (3S,7aR)-3-substituted-1-(4-nitrophenyl)tetrahydro-1H-pyrrolo[1,2-a]imidazol-2-ones 18a-c. Chiral (2S)-2-amino-2-substituted-N-(4-methylphenyl)acetamides 12a-d, easily prepared in two steps from N-Boc-alpha-amino acids 10a-d, similarly reacted with glutaraldehyde (20) and benzotriazole to generate 5-benzotriazolyl-3-substituted-hexahydroimidazo[1,2-a]pyridin-2(3H)-ones 21a-d, which were converted by sodium borohydride directly into optically active 3-substituted-hexahydroimidazo[1,2-a]pyridin-2(3H)-ones 22a-d.