Baeyer-Villiger-Including Domino Two-Step Oxidations of β-O-Substituted Primary Alcohols: Reflection of the Migratory Aptitudes of O-Substituted Alkyl Group in the Outcome of the Reaction

Tom Targel,Moshe Portnoy

doi:10.3390/catal10111275

Abstract

Following the recent development of the one-pot two-step oxidation protocol for primary β-alkoxy alcohols, additional primary β-oxy alcohols were examined under similar conditions. The outcome of these reactions closely follows the migratory aptitudes of the related α-oxy-alkyls in Baeyer-Villiger oxidation vs. that of hydrogen. Thus, these experiments helped to establish the correct order of these aptitudes for α-oxy-alkyls. Furthermore, in the case of primary β,β-dialkoxyalcohols, the formation of dialkoxymethyl formates by the domino oxidation reaction was followed by secondary reactions, forming a number of interesting products.

Highlights

Oxidation of secondary alcohols usually leads to ketones as end products [1], and only the Baeyer-Villiger (BV) reaction [2,3,4,5], inserting oxygen between the carbonyl and an adjacent carbon and, forming an ester with an interrupted carbon skeleton, could lead to an additional oxidation completing a two-step oxidation sequence [6,7,8,9,10,11,12,13,14,15,16,17,18,19]
TEMPOof one of the hydrolytic intermediates. These results prove that β,β-dialkoxy alcohols catalyzed oxidation of one of the hydrolytic intermediates (Scheme 6) [39]. These results prove that react in the domino oxidation reaction in a way similar to β-alkoxy alcohols, but form unstable products
In order to compare the aptitudes of α,α-dialkoxyalkyl and α-alkoxyalkyl, we examined the reaction of a secondary alcohol 1h with both groups flanking the hydroxyl-bearing carbon (Table 1, Entry 8)

Summary

Introduction

Oxidation of secondary alcohols usually leads to ketones as end products [1], and only the Baeyer-Villiger (BV) reaction [2,3,4,5], inserting oxygen between the carbonyl and an adjacent carbon and, forming an ester with an interrupted carbon skeleton, could lead to an additional oxidation completing a two-step oxidation sequence [6,7,8,9,10,11,12,13,14,15,16,17,18,19]. In the case of the primary alcohols, two-stage oxidation is much more common and leads predominantly to carboxylic acids [20], which are formed from aldehydes via the Baeyer-Villiger pathway or one of the alternative mechanisms at the second step. We reported an unprecedented and efficient one-pot procedure for transformation of primary β-alkoxy alcohols into the corresponding hemiacetal formates [32]. Secondary β-alkoxy alcohols can be converted in a one-pot fashion into hemiacetal esters [33]. This process, combining TEMPO-based catalytic and mCPBA-induced stoichiometric steps (Scheme 1a, TEMPO = (2,2,6,6-tetramethylpiperidin-1-yl)oxyl, mCPBA = m-chloroperbenzoic acid), reflects the stronger migratory aptitude of alkoxyalkyls compared to that of hydrogen or simple alkyl in the BV step

Methods

Results

Conclusion