An Efficient and Versatile Approach for Optical Resolution of C₂-Symmetric Axially Chiral Biaryl Dials. Synthesis of Enantiopure Biaryl-Derived Cyclic trans-1,2-Diols

Abstract

An efficient and practical method for optical resolution of axially chiral biaryl dials using enantiomeric tert-butanesulfinamide as resolving agent was developed. The approach offers a very convenient and straightforward access to versatile enantiomerically pure C2-symmetric biaryl dials in good yields. With the obtained axially chiral dials, stereoselective synthesis of a series of cyclic trans-1,2-diols in optically pure form was investigated.

Mechanistic Insights on the Stereoselective Nucleophilic 1,2-Addition to Sulfinyl Imines

“…The 1 E isomer is more stable than 1 Z by 10.0 kcal mol –1 , which is in agreement with the lack of observation of 1 Z . The calculated structure of 1 E compares well with the crystal structures of related systems, which all have an E conformation (Table ). − In 1 E , the CNSO dihedral angle is 14°, in excellent agreement with the average value of 14° observed in the crystal structures. A search for other conformations varying the CNSO dihedral angle identified a conformer, 1 Eb , 4.4 kcal mol –1 higher in energy.…”

“…The inversion barrier for the structurally similar compound Nethylidenesulfinamide has been calculated by Bharatam et al to be 24.2 kcal mol −1 at the B3LYP/6-31+G* level of theory. 8 For comparison, the inversion barrier of methyleneimine is 21 1.457(8) 1.255(5) 1.707(5) 1.470(5) 1.840(5) 8.1(4) VAHYOT 22 1.475(4)…”

Programmed serial stereochemical relay and its application in the synthesis of morphinans

“…In this context, the synthesis of biaryl aldehyde 4 was originally envisioned based on the desymmetrization of the readily accessible (and potentially optically active) dialdehyde 1 ( Scheme 2 ). 6 However, a more direct approach was later realized through one of the earliest illustrations of CH-activation chemistry pioneered by Dyker, 7 and the as-obtained biaryl system 3 underwent smooth benzylic oxidation (DDQ) to afford the targeted aldehyde 4 together with its equilibrating hemiacetal 4′ in 65% yield over the two steps. The phenolic aldehyde 4 (and 4′ ) was next subjected to a selection of organometallic reagents, and gratifyingly, each organometallic addition reaction afforded a separable mixture of two stereoisomers in high yield ( 5a / 5a′ – 5d / 5d′ , 85–97%).…”

Synthesis of Chiral and Modifiable Hexahydroxydiphenoyl Compounds

“…Despite the biological and chemosynthetic importance of the chiral HHDP compounds, their availability from natural sources is low because the isolation of a substantial amount of pure ellagitannin is generally difficult . Although many methods for synthesizing chiral HHDP compounds have been studied, − most of them adopt methyl groups to protect the phenolic hydroxy groups despite their difficult removal. Application of removable protecting groups on the HHDP compounds has been carried out in total syntheses of natural ellagitannins. − However, an effective and usable method of synthesizing both enantiomers of chiral HHDP was not presented in these works.…”