Wolfgang Oppolzer

Asymmetric alkylation of N-acylsultams: A general route to enantiomerically pure, crystalline C(α,α)-disubstituted carboxylic acid derivatives

Abstract Successive treatment of acylsultams 2 with nBuLi or NHMDS and primary alkyl halides, followed by crystallization, gave pure C(α)-alkylation products 4 and, via their non-destructive cleavage, enantiomerically pure alcohols 5 or carboxylic acids 6 .

Enantioselective synthesis of sec-allylalcohols by catalytic asymmetric addition of divinylzinc to aldehydes.

Readily available chiral tridentate ligand 8 catalyzes the highly Si-face selective addition of diethyl-, di-n-propylzinc and, more significantly, of divinylzinc to aromatic and aliphatic aldehydes whereas bidentate ligands 11 and 12 exert a topologically reversed catalytic bias.

Chiral toluene-2,α-sultam auxiliaries: Preparation and structure of enantiomerically pure (2R)- and (S)-ethyl-2,1′-sultam ☆

Abstract Crystalline sultams (R)- 2 or (S)- 2 were selectively prepared from prochiral saccharine ( 3 ) in two steps (53% overall yield) via Ru-(R)-BINAP- or Ru-(S)-BINAP catalyzed asymmetric hydrogenation of imine 4 . Alternatively, pure (R)- 2 was synthesized (37% overall yield) from (R)-α-phenethylamine in 4–5 steps involving the ortho-sulfination 6 → 7 and the highly diastereoselective cyclization of sulfinic acid 7 to the sulfinamide 8 . X-ray diffraction analyses of sulfinamide 8 and sultam (R)- 2 are presented.

Iridoids: enantioselective synthesis of loganin via an asymmetric Diels-Alder reaction

Abstract Starting from (-)-camphor-10-sulfonic acid ( 5 ) the crystalline sultam 9 was readily prepared. TiCl4-mediated Diels-Alder addition of the N-crotonoyl sultam 11 to cyclopentadiene, crys- tallization of the resulting adduct 12 and subsequent reduction gave virtually pure (1S, 4R, 5R, 6S)- 1 together with recovered auxiliary 9 . The loganin precursor 1 was transformed into norbornanone 20 , which upon Baeyer-Villiger oxidation led to the suitably substituted cyclo- pentane 22 from which 1-B-O-methyl loganin aglucone ( 2 ) was rea- dily available.

Asymmetric synthesis of α-amino acids and α-N-hydroxyamino acids via electrophilic amination of bornanesultam-derived enolates with 1-chloro-1-nitrosocyclohexane.

Successive treatment of N-acylsultams 3 with NaN(TMS)2, l-chloro-1-nitrosocyclohexane (1) and 1N aq. HCl gave diastereomerically pure, crystalline Nhydroxyamino acid derivatives 4. Products 4 were converted to various amino acids 6, an NBOC-amino acid 8 and to N-hydroxyamino acids 9. (S,S)-Isoleucine (16) was obtained from N-crotonoylsultam 13 via an organomagnesium- 1,4-addition/enolate trapping process generating two stereogenic centers.

Asymmetric diels-alder reactions : facile preparation and structure of sulfonamido-isobornyl acrylates

Abstract The crystalline chiral auxiliaries 2 , 3 and 4 were prepared from camphor-10-sulfonyl chlorides in 2 steps. Their readily accessible acrylates underwent efficient asymmetric diels-alder additions to cyclopentadiene, the topicity of which agrees with X-ray evidence.

Chiral toluene-2,α-sultam auxiliaries: Asymmetric diels-alder reactions of N-enoyl derivatives

Abstract Asymmetric, R m AlCl n mediated Diels-Alder reactions of 1,3-dienes to N -enoyl derivatives 4 and 9 of ( R )-methyl-, ( R,S )- t -butyl-, α,α-dimethylbenzyl-, benzyl and ( S )-methyl-toluene-2,α-sultams 3 as well as to N -enoyl derivatives 15 of ( R )-2,3-dihydro-3-methylisoindolinone 14 are described.

Chiral toluene-2,α-sultam auxiliaries: Asymmetric alkylations, acylations and aldolizations of N-acyl derivatives

Abstract Successive treatment of ( R )- N -acylsultams 4 with NHDMS/alkyl halides or NHDMS/acyl chlorides provides alkylated or acylated products 6 or 7 . Diastereoselective reductions of 7 with Zn(BH 4 ) 2 or NaHB( s Bu) 3 gives “ syn ”- or “ anti ”-aldols 8 or 9 . Reaction of 4 with BEt 3 /TfOH/EtN( i Pr) 2 followed by addition of aromatic or aliphatic aldehydes affords diastereomerically pure “ syn rd-aldols 10 . Non-destructive removal of auxiliary 3 from 6 , 8 , 9 and 10 yields enantiomerically pure products 12 to 16 .

Asymmetric alkylations of a sultam-derived glycinate equivalent: practical preparation of enantiomerically pure α-amino acids

Abstract Deprotonation/alkylation of sultam-derived N-[bis(methyl)thiomethylene]glycinate equivalent 3 gave crystalline products 5 which on mild hydrolysis furnished α-amino acids 7 (~100% e.e.) in high overall yield.

ENANTIOMERICALLY PURE, CRYSTALLINE ANTI-ALDOLS FROM N-ACYLBORNANESULTAMS :ALDOLIZATION AND STRUCTURE OF INTERMEDIATE T-BUTYLDIMETHYLSILYL-N,O-KETENE ACETAL

Abstract O-Silylation of N-propionylsultam 1 provides pure Z O-silyl-N,O-ketene acetal 2 which undergoes Lewis acid promoted addition of aromatic and aliphatic aldehydes to give diastereomerically pure, crystalline “anti” aldols 7 or their silylethers 3 . Hydroperoxide-assisted hydrolysis/esterification of products 7 yields enantiomerically pure methoxycarbonyl aldols ( 11 , 12 , 13 , 14 ).