Intramolecular CH-Hydrogen Bonding During the Dissociation of the Oxaphosphetane Intermediate Facilitates Z/E-Selectivity in Wittig Olefination

Abstract

Herein, DFT studies corroborating experimental results revealed that the shortest intramolecular hydrogen bonding distance of cis/trans-oxaphosphetane (OPA) oxygen with the CH-hydrogen of a triphenylphosphine phenyl ring provides good evidence for the attained olefin Z/E-selectivity in Wittig olefination of the studied examples. 2-Nitrobenzaldehyde, 3-nitrobenzaldehyde, 2-nitro-3-bromobenzaldehyde, 2-nitro-5-bromobenzaldehyde and 2-nitro-5-arylbenzaldehydes provided Z-nitrostilbenes with (2-chloro-4-hydroxy-3-methoxy-5-(methoxycarbonyl)benzyl) triphenylphosphonium chloride as the major products. However, 4-nitrobenzaldehyde and 2-nitro-6-bromobenzaldehydes furnished E-nitrostilbenes as the major products in high yields. Furthermore, the DFT computed intramolecular CH1/CH2-hydrogen bond distances with Cl/NO₂ of selected stilbene derivatives were in good agreement with intramolecular hydrogen bond distances measured from single-crystal X-ray diffraction measurements.

Keywords: 2-arylindoles; Wittig olefination; benzylphosphonium salts; hydrogen bonding; nitrostilbenes.

Figure 1

Wittig olefination of nitrobenzaldehydes.

Scheme 1

De novo synthesis of benzylphosphonium chloride salts 2 a–g.

Scheme 2

Synthesis of 2’/3’/4’‐nitro‐stilbene derivatives from 2 a.

Scheme 3

Synthesis of 3’/5’/6’‐bromo‐2’‐nitro‐stilbene derivatives.

Scheme 4

Synthesis of 5’‐aryl‐2’‐nitro‐stilbene derivatives.

Scheme 5

Reactivity of multi‐substituted aromatic aldehydes with Wittig salt 2 a.

Figure 2

Intramolecular CH‐hydrogen bond distances of X‐ray and DFT computed stilbenes (A) 4 a‐cis; (B) 4 b‐trans; (C) 5 b‐trans; (D) 6 b‐trans.

Scheme 6

A plausible mechanism for the Z‐selective formation of 5‘‐Br(H/Ar)‐2‘‐nitrostilbenes.

Scheme 7

Synthesis of 2‐aryl indole derivatives 12 a and 12 b.