Totalsynthese von natülichem α-Tocopherol. 5. Mitteilung. Asymmetrische Alkylierung und asymmetrische Epoxidierung als Methoden zur Einführung der (R)-Konfiguration an C(2) des Chroman-Systems

Total Synthesis of Naturally Occurring α-Tocopherol. Asymmetric Alkylation and Asymmetric Epoxidation as Means to Introduce (R)-Configuration at C(2) of the Chroman Moiety Based on the reductive, stereospecific ring closure of (2R,4′R,8′R)-α-Tocophcrylquinone′ or corresponding analogues with a short, functionalized side chain ( B , Scheme 1) to 1 resp. the chroman system of 1 (C), two different approaches for the introduction of the required tertiary methyl-substituted alcohol structure in the side chain of the aromatic precursors ( A , Scheme 1) were developed. The first approach uses asymmetric alkylation in three different versions featuring (a) diastereoselective steering with chiral auxiliaries I-IV (Scheme 2) attached as esters to a-keto acids, (b) intermediate transfer of chirality in an ester enolate (from 18 , Scheme 4) derived from an optically active α-hydroxy acid, (c) enantioselective alkylation of phytenal ( 20 ) and subsequent ring closure with chirality transfer (Schemes 5–7). The second approach is based on the asymmetric epoxidation of β-metallylalcohol (Sharpless epoxidation), the corresponding epoxyalcohol being converted in situ to the (S)-or (R)-chlorodiol (S)-and (R)- 29 , respectively, for isolation (Schemes 8 and 9). Nucleophilic epoxide opening with a (3R 7R)-3,7,11-trimethyldodecyl (C₁₅**) and an ArCH2 unit in appropriate sequence is used to assemble the C-framework of the target molecule via corresponding epoxide intermediates from either chlorodiol. Combined with the use of the methoxymethyl-ether function for protection of the hydroquinone system, the epoxide approach provides a short route to 1 (Scheme 10).     

Homogeneous and heterogeneous asymmetric reactions. Part 5. Diastereoselective and enantioselective hydrogenation of cyclic β-keto esters on modified Raney-nickel catalysts

The hydrogenations of methyl 2-oxoeyclopentanecarboxylate ( 1 ), ethyl 2-oxocyelohexanecarboxylate ( 3 ), and 2-methylcyclohexanone ( 5 ) on unmodified Raney-Ni catalyst lead predominately to the formation of the cis-hydroxy diastereoisomers of 2 , 4 , and 6 , respectively (Scheme 2). In the asymmetric hydrogenations on catalysts modified with chiral tartaric acid ((R, R )-C₄H₆O₆/Raney-Ni and (R, R)-C₄H₆O₆/NaBr/Raney-Ni), the predominance of the cis-isomer increases significantly. The hydrogenations of β-keto esters 1 and 3 proceed with an enantioselectivity of 10–15% on the modified catalysts, while the similar hydrogenation of 5 yields optically inactive 6 . The (1S,2R)-enantiomers of the cis-isomers of 2 and 4 are formed in larger quantity, whereas the (lR,2R)-enantiomers of the corresponding trans-isomers predominate (Scheme 1). The enantioselective formation of trans- 2 and trans- 4 can be interpreted mainly in terms of the asymmetric hydrogenation of cyclic β-keto esters through the keto form, while that of the corresponding cis-hydroxy esters proceeds through the enol form.     

A Facile Synthesis of Optically Pure (−)-(S)-Ipsenol Using a Chiral Titanium Complex

A stereocontrolled synthetic route to optically pure (?)-(S)-ipsenol ( 1 ), the pheromone of Pityokteines curvidens and various other bark-beetle species is described. Key step of the synthesis is an enantioselective aldol reaction using a chiral titanium–carbohydrate complex (Scheme 1). The carboxylate function of the optically pure β-hydroxy acid 5 thus obtained in mol quantities is then elaborated to the diene moiety by standard methodology (Scheme 2).     

Über die Stereoselektivität der α-Alkylierung von (1R, 2S) (+)-cis-2-hydroxy-cyclohexancarbonsäureäthylester

The Stereoselectivity of the α-Alkylation of (+)-(1R, 2S)-cis-Ethyl-2-hydroxy-cyclohexanecarboxylate In continuation of our work on the stereoselectivity of the α-alkylation of β-hydroxyesters [1] [2], we studied this reaction with the title compound (+)- 2 . The latter was prepared through reduction of 1 with baker's yeast. Alkylation of the dianion of (+)- 2 furnished (?)- 4 in 72% chemical yield (Scheme 1) and with a stereoselectivity of 95%. Analogously, (?)- 7 was prepared with similar yields. Oxidation of (?)- 4 and (?)- 7 respectively furnished the ketones (?)- 6 (Scheme 3) and (?)- 8 (Scheme 4) respectively, each with about 76% enantiomeric excess (NMR.). It is noteworthy that yeast reduction of rac- 6 (Scheme 3) is completely enantioselective with respect to substrate and product and gives optically pure (?)- 4 in 10% yield, which was converted into optically pure (?)- 6 (Scheme 3). The alkylation of the dianionic intermediate shows a higher stereoselectivity (95%) from the pseudoequatorial side than that of 1-acetyl- or 1-cyano-4-t-butyl-cyclohexane (71% and 85%) [9] or that of ethyl 2-methyl-cyclohexanecarboxylate (82%). The stereochemical outcome of the above alkylation is comparable with that found in open chain examples [1] [2]. Finally (+)-(1R, 2S)- 2 was also alkylated with Wichterle's reagent to give (?)-(1S, 2S)- 9 in 64% yield. The latter was transformed into (?)-(S)- 10 and further into (?)-(S)- 11 (Scheme 5). (?)-(S)- 10 and (?)-(S)- 11 showed an e.e. of 76–78% (see also [11]). Comparison of these results with those in [11] confirmed our former stereochemical assignment concerning the alkylation step.     

Optically active imidazole-containing polymers

In order to investigate the stereospecificity of enzyme-catalyzed reactions, an optically active copolymer of 4(5)-vinylimidazole and 2,5(S)-dimethyl-1-hepten-3-one was synthesized, and its effects on the solvolytic rates, in ethanol-water, of the p-nitrophenyl and 4-carboxy-2-nitrophenyl esters of 3(R)- and 3(S)-methylpentanoic acid and of the commercially available N-carbobenzoxy-(R)- and (S)-phenylalanine p-nitrophenyl esters were investigated. The optically active comonomer was prepared by thermal decomposition of solid (+)-1-piperidino-2,5(S)-dimethylheptan-3-one hydrochloride, which was obtained from the reaction of 2(S)-methylbutyllithium with 3-piperidino-2-methylpropionitrile. The 3(R)-methylpentanoic acid was prepared in 92% optical purity from L -alloisoleucine via diazotization in concentrated hydrobromic acid and subsequent reductive debromination with zinc amalgam in dilute hydrochloric acid. In the optically active copolymer-catalyzed solvolyses of the optically active esters performed at pH values of 6–8 no significant differences between the solvolytic rates of (R) and (S) isomers of substrates were observed. Poly-L -histidine was also employed as a catalyst for the solvolyses of these substrates. At pH 6.0 in ethanol–water the latter catalyst also failed to exhibit specificity towards (R) and (S) substrates.     

Preparation and Absolute Configuration of Some Iris Essential Oil Constituents of the 5-methylsafranic-acid series

The β-dienoate (+)-(5S)- 13a (86% ee; meaning of α and β as in α- and β-irone, resp.) was obtained from (?)-(5S)- 9a via acid-catalyzed dehydration of the diastereoisomer mixture of allylic tertiary alcohols (+)-(1S,5S)- 15 /(+)-(1R,5S)- 15 (Scheme 3). Prolonged treatment gave clean isomerization via a [1,5]-H shift to the α-isomer (?)-(R)- 16a with only slight racemization (76% ee; Scheme 4). In contrast, the SnCl₄-catalyzed stereospecific cyclization of (+)-(Z)- 6 to (?)-trans- 8a (Scheme 2), followed by a diastereoselective epoxidation to (+)- 11 gave, via acid-catalyzed dehydration of the intermediate allylic secondary alcohol (?)- 12 , the same ester (+)- 13a (Scheme 3), but with poor optical purity (13% ee), due to an initial rapid [1,2]-H shift. The absolute configuration of (?)- 16a–c was confirmed by chemical correlation with (?)-trans- 19 (Scheme 4). ¹³C-NMR Assignments and absolute configurations of the intermediate esters, acids, aldehydes, and alcohols are presented.     

Enzymatic resolution of flavanone oximes

The optically active (R)- and (S)-flavanones were prepared by an enzymatically enantioselective hydrolysis of (±)-flavanone oxime O-acylates employing lipases, followed by hydrolysis with acid.     

Synthese von optisch aktiven Carotinoiden mit 3,5,6-Trihydroxy-5-6-dihydro-β-Endgruppen

Syntheses of Optically Active Carotenoids with 3,5,6-Trihydroxy-5,6-dihydro β-End Groups For the specification of the relative and absolute configuration in carotenoids with 3,5,6-trihydroxy-5-6-dihydro β-end groups, several ionone derivatives and carotenoids bearing this end group were synthesized. Acid-catalyzed hydrolysis of (3S,5S,6R)– acetoxy-5,6-epoxy-5,6-dihydro-β-ionone ( 7 ) and of its (3S,5R,6S)-isomer ( 13 ) gave the diols 8 and 15 , respectively, with exclusive inversion at c(5) (Scheme 2). Compared to this, mild acid hydrolysis of caroten-5-6-expoxides in the presence of H₂O resulted in the formation of 5,6-diols with either inversion or retention of the configuration at C(6) (Scheme 3). Spectroscopic data allowed us to distinguish the relative configurations (3R*,5S*,6S*) (see A ), (3R*,5R*,6R*) (see B ), (3R*,5S*,6R*) (see C ), and (3R*,5R*,6S*) (see D ), of the 3,5,6-trihydroxy-5-6-dihydro β-end groups. Syntheses of the optically active carotene-hexols 20 and 21 and comparison with published data led to a revision of the structure of mectrazanthin (now formulated as 20 ), heteroxanthin (now formulated as 28 ), and further carotenoids with 3,5,6-trihydroxy end groups.     

Asymmetric Phase-Transfer Catalysis by Quaternary Ammonium Ions Derived from Cinchona-Alkaloid Analogs Containing 1,1′-Binaphthalene Moieties

The synthesis and catalytic properties of a new type of enantioselective phase-transfer catalysts, incorporating both the quinuclidinemethanol fragment of Cinchona alkaloids and a 1,1′-binaphthalene moiety, are described. Catalyst (+)-(aS,3R,4S,8R,9S)- 4 with the quinuclidine fragment attached to C(7′) in the major groove of the 1,1′-binaphthalene residue was predicted by computer modeling to be an efficient enantioselective catalyst for the unsymmetric alkylation of 6,7-dichloro-5-methoxy-2-phenylindanone ( 1 ; Scheme 1, Fig. 1). Its synthesis involved the selective oxidative cross-coupling of two differently substituted naphthalen-2-ols to afford the asymmetrically substituted 1,1′-binaphthalene derivative (±)- 17 in high yield (Scheme 3). Chromatographic optical resolution via formation of diastereoisomeric camphorsulfonyl esters and functional-group manipulation gave access to the 7-bromo-1,1′-binaphthalene derivative (−)-(aS)- 11 (Scheme 4). Nucleophilic addition of lithiated (−)-(aS)- 11 to the quinuclidine Weinreb amide (+)-(3R,4S,8R)- 8 afforded the two ketones (aS,3R,4S,8R)- 27 and (aS,3R,4S,8S)- 28 as an inseparable mixture of diastereoisomers (Scheme 6). Stereoselective reduction of this mixture with DIBAL-H (diisobutylaluminum hydride; preferred formation of the C(8)−C(9) erythro-pair of diastereoisomers with 18% de) or with NaBH₄ (preferred formation of the threo-pair of diastereoisomers with 50% de) afforded the four separable diastereoisomers (+)-(aS,3R,4S,8S,9S)- 29 , (+)-(aS,3R,4S,8R,9R)- 30 , (−)-(aS,3R,4S,8S,9R)- 31 , and (+)-(aS,3R,4S,8R,9S)- 32 (Scheme 6). A detailed conformational analysis, combining ¹H-NMR spectroscopy and molecular-mechanics computations, revealed that the four diastereoisomers displayed distinctly different conformational preferences (Figs. 2 and 3). These novel Cinchona-alkaloid analogs were quaternized to give (+)-(aS,3R,4S,8R,9S)- 4 , (+)-(aS,3R,4S,8S,9S)- 5 , (+)-(aS,3R,4S,8R,9R)- 6 , and (−)-(aS,3R,4S,8S,9R)- 7 (Scheme 7) which were tested as phase-transfer agents in the asymmetric allylation of phenylindanone 1 . Without any optimization work, (+)-(aS,3R,4S,8R,9S)- 4 was found to catalyze the allylation of 1 yielding the predicted enantiomer (+)-(S)- 3b in 32% ee. The three diastereoisomeric catalysts (+)- 5 , (+)- 6 , and (−)- 7 gave access to lower enantioselectivities (6 to 22% ee's), which could be rationalized by computer modeling (Fig. 4).     

Über die Stereospezifität der α-Alkylierung von β-Hydroxycarbonsäureestern. Vorläufige Mitteilung

About the Stereospecific α-Alkylation of β-Hydroxyesters It was found, that dianions derived from β-hydroxyesters with lithium diisopropylamide (LDA) at ?50 to ?20° were alkylated stereospecifically (Scheme 1). The stereospecificity was 95–98%, the threo-compound (threo -2, -3 and -4) being the main product. This was proved for threo -2 and -3 by preparing the β-lactones 7 and 8 , respectively, which were pyrolyzed to trans-1, 4-hexadiene (9) and trans-1-phenyl-2-butene (10) , respectively (Scheme 2). Moreover, the acid threo -6 from threo -3 was converted by dimethylformamide-dimethylacetal to cis-1-phenyl-2-butene (11) (s. footnote 6). The alkylation of α-monosubstituted β-hydroxyesters also turned out to be stereospecific. Reduction of 16 and 18 with actively fermenting yeast furnished (+) -17 and (+) -2. respectively (Scheme 4), which were each mixtures of the (2R, 3S)- and the (2S, 3S)-isomers. Alkylation of (+) -17 with allyl bromide yielded after chromatography (2S, 3S) -19 and of (+) -2 with methyl iodide (2R, 3S) -19 , the oxidation of which finally gave (S)-(?) -20 and (R)-(+) -20 , respectively.     

Synthesis of an Enantiomerically Pure 1,3‐Thiazole‐5(4H)‐thione and Its Stereoselective 1,3‐Dipolar Cycloaddition with an Azomethine Ylide

Starting from the enantiomerically pure 2H‐azirin‐3‐amines (R,S)‐ 4 and (S,S)‐ 4 , the enantiomeric, optically active 4‐benzyl‐4‐methyl‐2‐phenyl‐1,3‐thiazole‐5(4H)‐thiones (R)‐ 1 and (S)‐ 1 , respectively, have been prepared (Schemes 2 and 3). In each case, the reaction of 1 with N‐(benzylidene)[(trimethylsilyl)methyl]amine ( 2 ) in HMPA in the presence of CsF and trimethylsilyl triflate gave a mixture of four optically active spirocyclic cycloadducts (Scheme 4). Separation by preparative HPLC yielded two pure diastereoisomers, e.g., (4R,5R,9S)‐ 10 and (4R,5R,9R)‐ 10 . The regioisomeric compounds 11 were obtained as a mixture of diastereoisomers. The products were formed by a 1,3‐dipolar cycloaddition of 1 with in situ generated azomethine ylide 3 , which attacks 1 stereoselectively from the sterically less‐hindered side, i.e., with (R)‐ 1 the attack occurs from the re‐side and in the case of (S)‐ 1 from the si‐side.     

Synthesis of Optically Active Bifunctional Isoprenoid Building Blocks by Rhodium(I)-Catalyzed Asymmetric Allylamine to Enamine Isomerization

The application of the known asymmetric allylamine to enamine isomerization methodology to bifunctional C⁵-isoprenoid allylic amines of types IId and IIe (Scheme 1) is described. It is shown that a number of such substrates can be isomerized with enantioselectivities of > 90% ee. using cationie Rh¹ complexes containing (6. 6′-dimethylbiphenyl′2, 2′-diyl)bis(dipheny phosphine) (BIPHEMP; 9) as asymmetry-inducing ligand (Scheme 2, Tables 1 and 2). Synthetically most useful is the isomerization of the benzyloxy derivative 10a into the (E)-enamine 11a . This isomerization proceeds with very high enantioselectivity (98-99% ee) and affords, after enamine hydrolysis, the optically active 4-(benzyloxy)-3-methylbutanals ((R)- or (S)- 12 ) in chemical yields of ca. 90%. In conjunction, a short synthetic route to the starting material 10a has been developed which has a Pd-catalyzed amination of isoprene epoxide ( 30 ) as the key step. Thus, convenient and practical access to the optically active aldehydes (R)-and (S)- 12 is now at hand. These aldehydes are useful optically active bifunctional building blocks for isoprenoid homologation.     

L-Phenylalanine Cyclohexylamide: A simple and convenient auxiliary for the synthesis of optically pure α,α-disubstituted (R)- and (S)-amino acids

This work describes L -phenylalanine cyclohexylamide ( 5c ) as a simple, cheap, and powerful chiral auxiliary for the synthesis of a series of optically pure α,α-disubstituted (R)- and (S)-amino acids of type 1 , such as (R)- and (S)-2-methyl-phenylalanine ( 1a ), (R)- and (S)-2-methyl-2-phenylglycine ( 1b ), and (R)- and (S)-2-methylvaline ( 1c ; Scheme 3). These amino acids were efficiently transformed into the suitably protected and activated amino acid building blocks (R)- and (S)- 12b and (R)- and (S)- 12c (Scheme 4) which are ready for incorporation into peptides by solution or solid-phase techniques. Based on the crystal structures of 6b, 6c , and 7a belonging to the diastereoisomeric peptides series 6 and 7 , the absolute configurations of each member of the series were determined. β-Turn geometries of type II′ and I were observed for 6b and 7a , respectively, whereas 6c crystallized in an extended conformation. The impacts of side-chain variation on conformation and crystal packing of these triamides are discussed.     

Synthese von (+)-(5S, 6S)-Azafrin-methylester; absolute Konfiguration von Aeginetinsäure and von weiteren vicinalen Apocarotin-diolen

Synthesis of (+)-(5S, 6S)-Azafrin Methyl Ester; Absolute Configuration of Aeginetic Acid and of Further Vicinal Apocarotenediols We describe the synthesis of a series of optically active vicinal apo-β-carotenediols. Thus, starting from (+)-(5S, 6S)-5,6-dihydroxy-5,6-dihydro-β-ionone ( 2 ) we have prepared the (Z/E)-isomeric (+)-C₁₅-esters 7 and 8 , the (+)-retinoic derivatives 14 , 15 , 18 , 19 and (+)-methyl azafrinate ( 22 ), the enantiomer of the naturally occur-ring compound (s. Scheme 1). Our synthesis also establishes the absolute configura-tion of aeginetic acid ( 24 ), aeginetoside ( 25 ) and aeginetin ( 26 ), compounds isolated from the root parasite Aeginetia indica by Indian and Japanese workers (s. Scheme 2). The presented synthesis of optically active methyl azafrinate confirms our previous assignment [14] of the absolute configuration of azafrin ( 1a ), which was based on degradative evidence.     

Synthesen von optisch aktiven Carotinoiden mit einer (R)-4-Hydroxy-β-Endgruppe

Synthesis of Optically Active Carotenoids with (R)-4-Hydroxy β-End Groups We describe the synthesis of optically active iso-β-kryptoxanthin ( 12 ; (R)-β,β-caroten-4-ol), iso-α-kryptoxanthins 14 ((4R,6′RS)-β,ε-caroten-4-ol) and 16 ((4R,6′R)-β,ε-caroten-4-ol), 4′-hydroxyechinenone ( 18 ; (R)-4′-hydroxy-β,β-caroten-4-one), and isorubixanthin ( 20 ; (R)-β,ω,-caroten-4-ol), their 400-MHz-¹H-NMR spectra, CD spectra and HPLC behaviour.     

Synthesis of polynucleotide analogs by grafting optically active adenine,cytosine, and hypoxanthine derivatives onto polytrimethylenimine

A new family of polynucleotide analogs were prepared by grafting nucleic acid base derivatives onto polytrimethylenimine. Several new optically pure α-nucleic acid base substituted propanoic acids were prepared as pendant groups. The (R)-ethyl adeninylpropanoate was obtained from adenine and (S)-ethyl lactate by utilizing a diethyl azodicarboxylate-triphenyl phosphine method. Subsequent hydrolysis of the ester in aqueous acid gave the (R)-adeninylpropanoic acid without racemization. The reaction of cytosine sodium salt with (S)-ethyl 2-[(methylsulfonyl)oxy] propanoate produced the 20% racemized (R)-ethyl 2-(cytosin-1-yl)propanoate. The optically pure ester was obtained by recrystallization from ethyl alcohol, which was hydrolyzed in aqueous acid to give the (R)-acid with 66% enantiomeric excess. The (R)-2-(hypoxanthin-9-yl)propanoic acid was prepared by reaction of (R)-2-(adenin-9-yl)propanoic acid with sodium nitrite. The pendant groups were allowed to react with N-hydroxy compounds in the presence of dicyclohexylcarbodiimide to give the active esters. These active esters underwent reaction with N,N-dipropylamine to provide monomer model compounds. The pendant groups were grafted onto polytrimethylenimine by using the active ester method. The racemization reactions were observed in the grafting reactions. The resulting polymers showed a range of percent grafting from 60 to 80%.     

Total Synthesis of Racemic and Optically Active Compounds Related to Physostigmine and Ring-C Heteroanalogues from 3-[2′-(dimethylamino)ethyl]2,3-dihydro-5-methoxy-1,3-dimethyl-1H-indo l-2-ol

Oxindole 11 , obtained on 3-[2′-(dimethylamino)ethyl]alkylation of oxindole 12 , yielded, on stereoselective reduction with sodium dihydridobis(2-methoxyethoxy)aluminate, aminoalcohol 8 (Scheme 2). The quaternary methiodide 10 , obtained from 8 with MeI, gave, in nucleophilic displacements concurring with a Hofmann elimination, (±)-esermethole 6 , (±)-5-O-methylphysovenol ( 14 ), (±)-5-O-methyl-1-thiaphysovenol ( 15 ), and (±)-1-benzyl-1-demethylesermethole ( 16 ). Syntheses of (±)-1-benzyl-1-demethylphenserine ( 18 ), (±)-1-demethylphenserine ( 19 ), and (±)-phenserine ( 4 ) from 6 and 16 are described. Optically active 8a and 8b , obtained by chemical resolution, similarly gave the enantiomers 6a and 14a–16a of the (3aS)-series (prepared earlier from physostigmine ( 1a )) and their (3R)-enantiomers. The anticholinesterase activity of (±)- 4 , (±)- 18 , and (±)- 19 was compared with that of their optically active enantiomers.     

Synthesis of chiral azamacrocycles using the bis(α-chloroacetamide)s derived from chiral 1,2-diphenylethylenediamine

Optically active diphenyl-substituted tetraaza-12-crown-4 diamide ( 10 ), tetraaza-15-crown-5 diamide ( 12 ), tetraaza-18-crown-6 diamide ( 11 ), and hexaaza-18-crown-6 diamide ( 9 ) ligands were prepared by treating the appropriate secondary diamines with the (R,R)- and (S,S)- forms of 1,2-bis(N-methyl-α-chloracetamido)-1,2-diphenylethane ( 20 ). Macrocyclic diamides 9 and 10 were reduced to form the optically active diphenyl-substituted hexaaza-18-crown-6 ( 13 ) and tetraaza-12-crown-4 ( 14 ), respectively. Reduction of macrocyclic diamide ligands 11 and 12 gave a complex mixture of products from which the desired tetraaza-15-crown-5 and 18-crown-6 compounds could not be isolated. Dichloride 20 was prepared by treating the chiral forms of 1,2- diphenylethylenediamine with chloroacetic anhydride or chloroacetyl chloride. The crystal structures for the (R,R)-form of dichloride 20 and the (S,S)-forms of macrocycles 10 and 11 are reported.     

Enzyme-Mediated Preparation of the Single Enantiomers of the Olfactory Active Components of the Woody Odorant Timberol®

Enantiomerically pure (3S)- 3a and - 3b , the olfactory active forms of 1-(2,2,6-trimethylcyclohexyl)hexan- 3-ol, components of the commercial woody odorant Timberol ^®, are obtained by lipase-PS-mediated enantioselective acetylation of the allylic alcohols 6 and 7 and of the saturated alcohol 3 . These materials, as mixtures of diastereoisomers, provided (3R)-configured transformation products. However, whereas in the conversion of 6 and 7 there is no diastereoselection, 3 provided the acetate of (1′S,3R,6′R)- 3c much more rapidly than that of the diastereoisomer (1′R,3R,6′S)- 3d (Scheme 3). Inversion of the configuration at C(3) of the side chain of the olfactory inactive (3R)-materials obtained as acetates in the enzymic treatment of 6 , 7 , and 3 also provided, eventually, the desired olfactory active (3S)-products.     

Ring Enlargement and Sulfur‐Transfer Processes in SiO2‐Catalyzed Reactions of Thiocarbonyl Compounds with Optically Active Oxiranes

The reactions of 1,3‐dioxolane‐2‐thione ( 3 ) with (S)‐2‐methyloxirane ((S)‐ 1 ) and with (R)‐2‐phenyloxirane ((R)‐ 2 ) in the presence of SiO₂ in anhydrous dichloroalkanes led to the optically active spirocyclic 1,3‐oxathiolanes 8 with Me at C(7) and 9 with Ph at C(8), respectively (Schemes 2 and 3). The analogous reaction of 1,3‐dimethylimidazolidine‐2‐thione ( 4a ) with (R)‐ 2 yielded stereoselectively (S)‐2‐phenylthiirane ((S)‐ 10 ) in 83% yield and 97% ee together with 1,3‐dimethylimidazolidin‐2‐one ( 11a ). In the cases of 3‐phenyloxazolidine‐2‐thione ( 4b ) and 3‐phenylthiazolidine‐2‐thione ( 4c ), the reaction with (RS)‐ 2 yielded the racemic thiirane (RS)‐ 10 , and the corresponding carbonyl compounds 11b and 11c (Scheme 4 and Table 1). The analogous reaction of 4a with 1,2‐epoxycyclohexane (= 7‐oxabicyclo[4.1.0]heptane; 7 ) afforded thiirane 12 and the corresponding carbonyl compound 11a (Scheme 5). On the other hand, the BF₃‐catalyzed reaction of imidazolidine‐2‐thione ( 5 ) with (RS)‐ 2 yielded the imidazolidine‐2‐thione derivative 13 almost quantitatively (Scheme 6). In a refluxing xylene solution, 1,3‐diacetylimidazolidine‐2‐thione ( 6 ) and (RS)‐ 2 reacted to give two imidazolidine‐2‐thione derivatives, 13 and 14 (Scheme 7). The structures of 13 and 14 were established by X‐ray crystallography (Fig.).