Highly Diastereoselective Synthesis of trans-2,5-Disubstituted Tetrahydrofurans

Abstract

trans-2,5-Disubstituted tetrahydrofurans were obtained as major diastereomers (trans/cis ratio 90:10-100:0) when acetylated gamma-lactols derived from (S)-glutamic acid were treated with titanium enolates of N-acetyl (R)-oxazolidin-2-thiones. A simple transesterification allowed us to obtain the corresponding methyl esters and recover the chiral auxiliary.

Vanadium‐Catalyzed Asymmetric Oxidation of Sulfides Using Schiff Base Ligands Derived from β‐Amino Alcohols with Two Stereogenic Centers

“…With the expectation that the enantioselectivity might be substantially influenced by structural changes in the ligands, we prepared Schiff base ligand 2 and ligands 3a-i (Scheme 1) according to a literature method for evaluation. [25,26] Ligand 2, derived from a β-amino alcohol with one stereogenic center, afforded poor enantioselectivity (3 % ee). In contrast, ligand 3a, derived from a β-amino alcohol with two stereogenic centers, gave the desired product with enhanced enantioselectivity (61 % ee) at room temperature.…”

“…[8] We wish to investigate the structural influence of the β-amino alcohol moiety, especially those with two stereogenic centers, to find a highly efficient catalyst system for this reaction. Because phenylalanine is a very cheap, commercially available material that can be modified to different target products with routine procedures, [25,26] we chose it as the starting material for the screening of the amino alcohols with two stereogenic centers for the enantioselective oxidation of sulfides.…”

Highly Diastereoselective Aldol Reaction with α‐CF3‐Substituted Enolates

“…Thus we first examined the formation of the titanium enolate of the α‐CF 3 ‐substituted amide 1 , and its reactivity towards 4‐nitrobenzaldehyde ( 2 a ) (Table 1). The preparation of the required 4‐benzyloxazolidine‐2‐thione was straightforward and followed reported procedures 6. Quantitative N‐acylation was achieved by treatment with 3,3,3‐trifluoropropanoic acid in the presence of N , N ′‐dicyclohexylcarbodiimide (DCC) and a catalytic amount of 4‐dimethylaminopyridine (DMAP) in dichloromethane at 0 °C.…”

Stereoselective addition of chiral titanium enolates to 5-substituted five-membered oxocarbenium ions

“…Due to the importance of these molecules, considerable effort has been devoted toward the development of methods for the stereoselective construction of 2,5-substituted tetrahydrofurans. Addition of nucleophiles such as Grignard reagents, 8 organozinc reagents, 9 and titanium enolates 10,11 to oxocarbenium ions derived from -lactol derivatives have been broadly employed in the stereoselective construction of tetrahydrofurans. [12][13][14] Recent studies have led to the development of models to explain and predict the stereochemical outcome of nucleophilic additions to oxocarbenium ions.…”