Highly stereoselective chlorination of β-substituted cyclic alcohols using PPh3–NCS: factors that control the stereoselectivity

Abstract

A variety of trans-beta-substituted cyclic alcohols were stereoselectively chlorinated to either the corresponding cis-chloride or trans-chloride (inversion or retention of configuration) with good to excellent yields; the stereochemical outcome is determined by the size of the ring and the nature of the beta-substituents, especially the electronegativity of the substituted atom.

Halogenative kinetic resolution of β-amido alcohols: chiral BINAP-mediated SN2 displacement of hydroxy groups by chlorides with inversion of stereochemistry

“…The cis-stereochemistry of the b-amido chloride (1R,2S)-cis-2 was confirmed by comparing its 1 H and 13 C NMR values with the literature reports. 9,12 The trans-chloride was not observed in the reaction. The strong electron-withdrawing nature of sulfonamide group prevented the neighbouring group participation ability of the amino group which resulted in an optically active cis-chloride with an inversion of stereochemistry.…”

“…As part of our ongoing research towards finding a suitable method for the halogenative kinetic resolution of racemic amino alcohols to produce optically active bamino chloride, we found that having a strong electron-withdrawing group on the amine will provide cis-chloride with inversion of configuration. 9 Herein, we report the enantioselective non-enzymatic kinetic resolution of amido alcohols through S N 2 displacement of the hydroxy group by halides with halogenating agents in the presence of commercially available chiral diphosphine BIN-AP and NCS which produces both optically active recovered transamido alcohols and cis-chlorides with an inversion of configuration (Scheme 2).…”

Novel isolated, L-amino acid-ligated rhodium catalysts that induce highly helix-sense-selective polymerization of an achiral 3,4,5-trisubstituted phenylacetylene

“…2) of the Rh(cod)(L-Val) in DMSO-d 6 , the methyl peaks of the L-valine residue appeared at d 0.93 and 0.99 ppm. Since the chemical shifts of the olefinic and methylene protons in cod also shifted to d 4.08, 2.30, and 1.71 ppm 8,31,32 (Fig. 2), respectively, the coordination of L-Val residue is also supported.…”

On the halogenation of N (1), N (2)-di- t -Boc-5-hydroxy-piperazic acid esters and the conformational preferences of their 5-halo-piperazic acid products. The importance of A 1,3 rotameric-strain in determining N (2)-acyl piperazic acid ring conformation

“…We have also proven that N(1), N(2) or C(3)-CO2Me mediated neighboring-group participation does not occur in the Ph3P-mediated halogenation of 5-hydroxy-N(1),N(2)-di-Nacylated piperazic acid derivatives, nor do these substitutions proceed via the SNi mechanism. Indeed, such reactions always proceed with stereochemical inversion, 12 as was indicated in our 1998, 5 2000 5 and 2011 9 literature reports. We have also provided here, for the very first time, an unambiguous explanation of how the rotameric A 1,3 -effect can dramatically affect piperazic acid ring conformation in N(2)-acyl piperazic acid derivatives, 16 and we have definitively shown how this effect can force the adoption of a seemingly disfavored chair that places the C(3)-carboxy in an axial orientation.…”

“…12 Specifically, the process afforded the trans-configured chloride 6 that had previously been synthesized by us 5 in 61% yield, alongside a small quantity (8%) of the 4,5-cycloalkene 5. 5 The latter arose from an anti-E2 elimination of the axial H4 and Ochlorophosphorane groups in the 6 C3 chair conformation, where the C(3)-carboxymethyl is axial.…”