关键词： amino alcohols   amino acids   asymmetric synthesis  

摘要： We describe a new method for the asymmetric synthesis, from allylic sulfoximines and aldehydes, of N,O-protected, cyclic and acyclic, beta-substituted and beta,beta-disubstituted delta-hydroxy-beta-amino acids and of N,O-protected 1,3-amino alcohols, both possessing three contiguous stereogenic centers. Treatment of enantiomerically pure, acyclic allylic sulfoximines with aldehydes after successive lithiation and titanation afforded sulfonimidoyl-substituted homoallylic alcohols with high regio- and diastereoselectivities. Diastereomerically pure, cyclic, sulfonimidoyl-substituted homoallylic alcohols were synthesized in a similar manner from the corresponding enantiomerically pure, cyclic allylic sulfoximmes and isobutyraldehyde. A highly chastere o selective amination of the sulfonimidoyl-substituted homoallylic alcohols with the generation of secondary and tertiary C atoms and formation of the sulfonimidoyl-substituted, protected 1,3-amino alcohols (oxazinones) was achieved by the carbamate method, through cyclization of the corresponding carbarnates after their lithiation with nBuLi. The sulfonimidoyl-substituted, monocyclic and bicyclic oxazinones were converted into protected, acyclic and cyclic, beta-substituted and beta,beta-disubstituted beta-amino acids and protected 1,3-amino alcohols by two different routes: the carbanion route and the substitution route. The carbanion route involves: (1) a double lithiation of the protected beta-amino sulfoximines, (2) treatment of the dilithiated sulfoximines with electrophiles, and (3) reductive removal of the sulfonimidoyl group. By the carbanion route, double lithiation of the sulfommidoyl-substituted oxazinones with nBuLi gave the corresponding dilithium. salts, which re-acted readily with a number of electrophiles to give the corresponding alpha-substituted sulfoximines in good yields. Reduction of the sulfoximines with Raney nickel afforded the corresponding protected monocyclic and bicyclic 1,3-amino alcohols an

关键词： RING formation (Chemistry)   PROLINE   AMINO compounds  

摘要： The amino-zinc-enolate cyclization reaction is a straightforward route for the synthesis of 3-substituted prolines. As classical intramolecular carbometalation reactions, the applicability of the addition of zinc to a double bond was limited to a substrate in which the terminal alkene carbon was unsubstituted. Being interested in the synthesis of cis- and traps-3-prolinoleucine derivatives for our structure-activity relation (SAR) studies, we focused our effort on the preparation of these compounds by amino-zinc-enolate cyclization of terminally substituted double bonds. Herein we report that the attachment of an activating group such as cyclopropyl to the terminal olefin carbon allows the amino-zinc-enolate cyclization of a terminally substituted alkene. The reaction is stereospecific, leading to a trans-3-substituted proline derivative, whereas a cis stereochemistry was observed with the amino-zinc-enolate cyclization of terminally nonsubstituted olefins. Absolute configurations obtained for the 3-prolinoleucine were established by X-ray analysis, NMR, and optical activity comparison of the cis and trans derivatives obtained by an unambiguous pathway.

关键词： Hydrocarbons   Reaction products   Diols   Molecular structure   Selectivity  

摘要： Starting from D-mannitol, we have prepared several C-2-symmetric ethanotethered bis(alpha,beta-butenolides) and studied their [2+2] photocycloaddition reaction with ethylene. The protective groups of the central diol unit have a noticeable influence on the facial selectivity of the cycloaddition, the bis(trimethylsilyloxy) derivatives showing the highest diastereoselectivity. A theoretical conformational analysis of the substrates in the ground state is in good agreement with the diastereofacial selectivity experimentally observed. The bis(photocycloadducts) have been converted into the enantiopure cyclobutanes formally derived from the photoreaction of ethylene with gamma-hydroxymethyl-alpha,beta-butenolide, in which only a moderate facial selectivity had been previously found. As an application of these studies, we have developed a highly efficient and stereoselective synthesis of (+)-grandisol.

关键词： DARZENS reaction   CHLOROMETHYL group   ANIONS  

摘要： An aza-Darzens reaction, involving the addition of chloromethylphosphonate anions to enantiopure sulfinimines, has been developed for the asymmetric synthesis of aziridine 2-phosphonates. Best results involve cyclization of the syn and anti diastereomerically pure alpha-chloro-beta-amino phosphonates to cis- and trans-N-sulfinyl aziridine 2-phosphonates, respectively, with n-BuLi. A transition-state hypothesis is proposed wherein the chloromethylphosphonate anion adds to the C-N bond on the side that is opposite the bulky p-tolyl sulfinyl group. The N-sulfinyl group is easily removed by treatment with MeMgBr or TFA/MeOH, which affords the NH-aziridines in good yield. Using transfer hydrogenation conditions, the NH-aziridines were regioselectively opened to the corresponding enantiopure alpha-amino phosphonates without N-activation and in excellent yield.

关键词： Lactones   Stereoselectivity   Catalysts   Molecular structure   Metathesis  

摘要： Bicylic and tricyclic gamma-butyrolactones with 5,7-, 5,6,5-, 5,6,6-, or 5,7,5-fused ring systems, being found in xanthanolides, eudesmanolides, and guaianolides, were readily synthesized from methyl furan-2-carboxylic acid. Key steps were a copper(I)-catalyzed asymmetric cyclopropanation, Sakurai allylations, intramolecular ene reactions, and ring-closing metathesis reactions.

关键词： synthesis   Sedum   carbonyl compounds   amides   enolate   condensation   Asymmetric synthesis   POTASSIUM ENOLATE  

摘要： N-Sulfinyl beta-amino Weinreb amides are prepared by condensation of sulfinimines with the potassium enolate of N-methoxy-N-methylacetamide. These new chiral building blocks are useful for the asymmetric synthesis of beta-amino carbonyl compounds, as illustrated here by the concise enantioselective syntheses of sedum alkaloids (+)-sedridine and (-)-allosedridine.

关键词： KETONES   OXAZOLES   ENANTIOMERS   ALCOHOLS (Chemical class)   NITRO compounds  

摘要： It is demonstrated that alpha,alpha-disubstituted-alpha-nitroketones are reduced to the corresponding trisubstituted nitro alcohols in good to excellent yield and enantiomeric excess by borane-dimethyl sulfide in the presence of a chiral oxazaborolidine catalyst. Reduction of the nitro alcohols to the corresponding amino alcohols and their subsequent conversion to enantiomerically enriched 4,4,5-trisubstituted oxazoldinones is also reported.

关键词： amino acids   asymmetric synthesis   chiral auxiliaries   nickel   nitrocyclopropylalanine  

摘要： All four diastereomers of 3 - (trans-2-nitrocyclopropyl) alanine (3) were prepared by asymmetrically induced a-C alkylation of the glycine moiety in the [(S)- or (R)-Schiff base]Ni-II complex 7, employing racemic trans-1-(iodomethyl)-2-nitrocyclopropane (8) as the alkylating agent. A notable difference in solubility between the two diastereomeric products 9a/9b [when (S)-7 was used as starting material] or 9d/9e [when (R)-7 was employed] allowed for their separation from the same reaction mixture. All the diastereomers of 3-(trans-2nitrocyclopropyl)alanine (3) were produced upon brief exposure of the alkylation products 9 to dilute hydrochloric acid, with subsequent purification by ion-exchange chromatography and crystallization. The absolute configurations of the nickel complexes 9a-e were established by X-ray crystallographic analyses. In addition, the X-ray crystal structure of (2S,1'S,2'R)-3 was determined to confirm the convergence of the configurations of the parent nickel complexes 9 with those of the amino acids 3 derived from them. (C) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003.

关键词： asymmetry   conjugate addition   copper   dialkylzinc   N-heterocyclic carbenes   Michael acceptors  

摘要： Chiral N-heterocyclic carbenes are good ligands for the copper-catalyzed conjugate addition of dialkylzinc reagents to various Michael acceptors. With as little as 4% of chiral ligand, the enantioselectivity may reach 93% on cycloheptenone.

关键词： Skeletons   Pyridines   Ketones   pyridine derivative   bone structure   Asymmetric synthesis   Antibiotic   lactone derivative  

摘要： Stoichiometric asymmetric reduction of the ketone group of a 2-acetyl-3,6-disubstituted pyridine derivative with an oxazaborolidine and N-ethyl-N-isopropyl aniline-borane complex gave the corresponding (S)-lactone derivative 5 in 96% ee almost quantitatively. Hydrogenolytic cleavage of 5 gave the expected (S)-2-(1-hydroxyethyl)pyridine derivative.