RESUMO
The doubly diastereoselective [3,3]-sigmatropic aza-Claisen rearrangement of silylketene aminals derived from 5-substituted (3S,4E,alphaR)-1-benzyloxy-3-[N-acyl-N-(alpha-methylbenzyl)amino]pent-4-enes furnishes 2,3-disubstituted (R)-N-alpha-methylbenzyl (2S,3R,4E)-7-benzyloxyhept-4-enamides in >90% de under the "matched" control of both stereogenic centres. Rearrangement of the "mismatched" diastereomeric (3R,4E,alphaR)-substrates proceeds with low diastereoselectivity. The substrate scope of the doubly diastereoselective rearrangement of the "matched" substrates in which two new stereogenic centres are created has been delineated.
RESUMO
Integration of a (13)C-(1)H satellite peak of a given (12)C-(1)H parent resonance within a quantitative (1)H NMR spectrum and comparison to the minor component represents a simple protocol for the accurate determination of diastereoisomeric ratios of up to 1000:1 (i.e., 99.8% de).
RESUMO
The incorporation of a gem-dimethyl group at the 5-position of a chiral oxazolidinone biases the conformation of the adjacent C(4)-stereodirecting group such that the gem-dimethyl-4-iso-propyl combination mimics a C(4)-tert-butyl group, providing higher levels of stereocontrol than a simple 4-iso-propyloxazolidinone. The generality of this principle is demonstrated with applications in stereoselective enolate alkylations, kinetic resolutions, Diels-Alder cycloadditions and Pd-catalysed asymmetric acetalisation reactions.
RESUMO
Conjugate addition of lithium dibenzylamide to methyl 5-isopropyl, 5-phenyl- and 5-tert-butyl-cyclopentene-1-carboxylates occurs with high levels of substrate control (>88% de), with preferential addition to the face of the cyclic alpha,beta-unsaturated acceptor anti- to the stereodirecting 5-alkyl substituent. Treatment of a range of methyl (+/-)-5-alkyl-cyclopentene-1-carboxylates with both lithium (+/-)-N-benzyl-N-alpha-methylbenzylamide and lithium (+/-)-N-3,4-dimethoxybenzyl-N-alpha-methylbenzylamide indicates significant enantiorecognition in their mutual kinetic resolutions, with preferential addition anti- to the 5-alkyl substituent, giving the 1,2-syn-1,5-anti-arrangement (E >16) after enolate protonation anti- to the amino functionality. The kinetic resolution of a range of methyl (+/-)-5-alkyl-cyclopentene-1-carboxylates with lithium (S)-N-benzyl-N-alpha-methylbenzylamide, and their efficient parallel kinetic resolution with a pseudoenantiomeric mixture of lithium (S)-N-benzyl-N-alpha-methylbenzylamide and lithium (R)-N-3,4-dimethoxybenzyl-N-alpha-methylbenzylamide are also demonstrated, giving a range of 5-alkyl-cispentacin derivatives in >98% de and high ee after N-deprotection.
RESUMO
Diketopiperazinespirocyclopropane 12 is prepared in > 98% d.e. via the conjugate addition of a phosphorus ylide to (6S)-N,N'-bis(p-methoxybenzyl)-3-methylenepiperazine-2,5-dione 2. Deprotection and hydrolysis of adduct 12 and subsequent peptide coupling demonstrate the applicability of this methodology to the asymmetric synthesis of 1-aminocyclopropane-1-carboxylic acids for incorporation into novel peptides. A model for the high level of diastereofacial selectivity observed in the cyclopropanation reaction is presented. A highly selective asymmetric approach (> 98% d.e.) to (S)-[2,2-(2)H2]-1-aminocyclopropane-1-carboxylic acid 29 is also reported via a deuterated sulfur ylide addition to acceptor 2.
RESUMO
Asymmetric [3,3]-sigmatropic aza-Claisen rearrangement of the (Z)-N-allyl-N,O-silylketene aminal of (3S,4E,alphaR)-1-benzyloxy-3-(N-propionyl-N-alpha-methylbenzylamino)hex-4-ene furnishes (2S,3R,4E,alphaR)-N-alpha-methylbenzyl-2,3-dimethyl-7-benzyloxyhept-4-enamide in > 92% d.e.; rearrangement of the diastereomeric (3R,4E,alphaR)-(Z)-N,O-silylketene aminal proceeds with low diastereoselectivity.