Christoph Schneider

New Polyol Syntheses

1,3,5,…︁-Polyol structures are characteristic components of polyene macrolide antibiotics such as filipin III (1). Iterative stereoselective alkylation of lithiated cyanohydrin acetonides and subsequent reductive decyanation is one possibility for the stepwise synthesis of this class of natural products characterized by a polyol framework of 1,3-diol units.

Lewis base-catalyzed addition of triethylaluminum to epoxides

Abstract Lewis bases like phosphines, arsines, and antimonies catalyze the nucleophilic addition of triethylaluminum to epoxides very efficiently. They are proposed to coordinate to triethylaluminum with formation of monomeric and more reactive triethylaluminum Lewis base adducts.

Stereodivergent Synthesis of Highly Substituted Tetrahydropyrans

Intramolecular oxa-conjugate addition has been employed in a stereoselective synthesis of enantiopure polyalkyl-substituted tetrahydropyrans, which are frequently found as substructures in many natural products. The requisite cyclization precursors, 7-hydroxy-2-enimides 3 and 7-hydroxy-2-enoates 6 were easily accessible by silyloxy Cope rearrangements of the appropriate chiral syn-aldols. It was found that the stereoselectivity of the cyclization could be controlled by judicious choice of the carboxylic acid derivative, resulting in a kinetically controlled reaction for the imides and a thermodynamically controlled process for the esters. Mechanistic considerations that could account for the stereocontrol of the process are outlined.

Highly stereoselectively cope rearrangements of enantiomerically pure, silylated syn-aldols

Abstract Enantiomerically pure, 1,6-disubstituted 1,5-dienes 3a–k with an aldol subtitution pattern undergo rapid thermal Cope rearrangements with very high diastereoselection (up to 97.3) and in very good yield.

Enantioselective Polyol Synthesis via the Cope Rearrangement of Chiral Aldol Products. A Synthesis of the C1-C10-Fragment of Nystatin A1

Abstract A stereoselective synthesis of a fully protected C1-C10-polyol-fragment of nystatin A1 is described. The oxy-Cope rearrangement of the chiral aldol product 1 affords the aldehyde 3 as the key intermediate which is converted into the natural product fragment by enantioselective allylboration and intramolecular conjugate addition of a hemiacetal-alkoxide.

Highly stereoselective and efficient synthesis of functionalized cyclohexanes with multiple stereocenters.

Chiral 7-oxo-2-enimides 2, which were readily obtained through a silyloxy-Cope rearrangement of syn-aldol products 1, have proved to be versatile substrates for a one-step, highly efficient and stereoselective synthesis of functionalized cyclohexanes. Organocopper and organoaluminum reagents have been employed as nucleophiles that underwent a conjugate addition to the enimide structure of the Cope products. The enolates formed in situ attacked the aldehyde or iminium ion in an intramolecular aldol or Mannich reaction, respectively, to directly yield cyclohexanols 3 and 4 and cyclohexylamines 5, respectively, in moderate to good yields and with excellent stereocontrol.

Stereoselective Synthesis of Highly Substituted Piperidines

Enantiopure piperidines 4 may be accessed in very good overall yields and high stereoselectivity from the bifunctional products 2 of the silyloxy Cope rearrangement of chiral aldol products 1 by sequential nucleophilic addition of primary amines and subsequent hydrogenation. The reaction is proposed to proceed by initial imine formation followed by an intramolecular aza-conjugate addition to the α,β-unsaturated imide. The stereoselectivity is controlled by A(1.2) strain between the imine N-alkyl group and the conjugate double bond. In an alternate approach, polyalkyl-substituted piperidines were prepared by the addition of organozinc reagents to cyanopiperidines readily obtained from the Cope products in the presence of a silver salt.

Zr(OtBu)4-catalysed synthesis ofacetone aldol adducts and domino aldol-Tishchenko reactions with diacetonealcohol as enol equivalent

Zr(OtBu)4 was found to be a potent catalyst for the synthesis of acetone aldol adducts with diacetone alcohol as enol equivalent and for domino aldol-Tishchenko reaction giving rise to 1,3-anti-diol monoesters with excellent diastereoselectivity.

Structures of endo- and exo-3-acetoxy-2,4-diethoxy-6-(2-oxo-1,3-oxazolidin-3-ylcarbonyl)-3,4-dihydro-2H-pyran

The crystal structures of (+)-(2fl,3fl,43)- and (4-)- (2a,3a,4fl)-2,4-diethoxy-6-(2-oxo-l,3-oxazolidin-3-yl- carbonyl)-3,4-dihydro-2H-pyran-3-yl acetate (the endo compound with half a molecule of diethyl ether in the asymmetric unit) determined at 153 and 293 K, respec- tively, are reported. The two structures have similar bond lengths and angles and similar conformations.