Synthesis of Enantiomerically Pure 2-Heteroaromatic-Substituted 1,2-Amino Alcohols from Chiral tert-Butanesulfinyl Aldimines

Abstract

Nine R/S pairs of 2-heteroaromatic-substituted 1,2-amino alcohols were synthesized through 1,2-nucleophilic addition between chiral N-(tert-butylsulfinyl)imines and heteroaromatic carbanions. In most cases, the R S-isomer of N-(tert-butylsulfinyl)imines afforded the R amino alcohol from deprotection of the major diastereomer, and S Simines afforded the S product. In general, this procedure allows for the preparation of a variety of enantiomeric pairs of 2-heteroaromatic-substituted 1,2-amino alcohols on a practical scale (>10 g) in two steps in good yields.

Regioselective Electrophilic Fluorination of Rationally Designed Imidazole Derivatives

“…In an initial attempt to investigate the direct fluorination of substituted imidazole derivatives, we selected 2-chloro-1-(ethoxymethyl)-1 H -imidazole 1a as model substrate with N -fluorobenzenesulfonimide (NFSI) 2 as electrophilic fluorinating reagent , and tetrahydrofuran (THF) as polar aprotic solvent (Table ). The introduction of chlorine at position C2 provides an electron-deficient functionality acting also as a cleavable protecting group, potentially facilitating the direct fluorination at C5.…”

Chiral N‐tert‐Butylsulfinyl Imines: New Discoveries

“…When the starting sulfinyl imine contains a α‐DTBSO group, the reaction with different lithiated heterocycles led to the formation of protected chiral 1,2‐amino alcohols [22] . In the case of anisole ( 26 ), after lithiation with Bu n Li, the reaction with imines 16 led to the formation of the expected compounds 27 with high stereoselectivities (Scheme 11).…”

A Magnesium-Based Diastereoselective Preparation of Pyridylic 1,3-Amino Alcohols Using the tert-Butyl Sulfinamide Auxiliary

“…Whereas the preparation of chiral 1,2-amino alcohols has been described in detail, 5,9,[11][12][13] syntheses of 1,3-amino alcohols using a common precursor are much less abundant. Our first approach towards the synthesis of 1c using lithium-based chemistry did not afford any of the desired product, likely as a result of the elimination of HF from the trifluoroethoxy functionality, which has often been noted; 14 thus, the development of a milder magnesium-based protocol was desired.…”