New Strategies in Carbonylation Chemistry:  The Synthesis of δ-Lactones from Saturated Alcohols and CO

Abstract

This paper describes the δ-carbonylation of saturated alcohols which uses a 1,5-hydrogen-transfer reaction of alkoxyl radicals and subsequent carbonylation at the δ-carbon atoms as the key. The carbonylation reactions of five classes of saturated alcohols, namely, primary alcohols having primary δ-carbons, primary alcohols having secondary δ-carbons, primary alcohols having tertiary δ-carbons, secondary alcohols having primary δ-carbons, secondary alcohols having secondary δ-carbons, were carried out, in which lead tetraacetate (LTA) was used as a one-electron oxidant to generate the alkoxyl radicals. Carbonylation of these saturated alcohols, except for primary alcohols having tertiary δ-carbons, took place to afford δ-lactones in moderate to good yields. The mechanism of the remote carbonylation likely involves (1) alkoxyl radical generation via LTA oxidation of a saturated alcohol, (2) conversion of this alkoxyl radical to a δ-hydroxyalkyl radical by a 1,5-hydrogen-transfer reaction, (3) CO trapping of the δ-hydroxyalkyl radical yielding an acyl radical, and (4) oxidation and cyclization of the acyl radical to give a δ-lactone. A metal salt-free system was also tested for a substrate derived from a tertiary alcohol having a secondary δ-carbon; the photolysis of an alkyl 4-nitrobenzenesulfenate under CO pressures gave a δ-lactone in moderate yield.

Synthesis of Functionalized Heterocycles via Oxidative Carbonylation

“…Primary alcohols having primary δ-carbons, primary alcohols having secondary δ-carbons, secondary alcohols having primary δ-carbons, and secondary alcohols having secondary δ-carbons all underwent carbonylation to afford δ-lactones in moderate to good yields. The mechanism of this carbonylation involves (1) oxidation of a saturated alcohol by LTA to generate alkoxyl radicals, (2) conversion of this alkoxyl radical to a δ-hydroxyalkyl radical via a 1,5-hydrogen-transfer reaction, (3) generation of an acyl radical by CO trapping of the δ-hydroxyalkyl radical, and (4) oxidation and cyclization of the acyl radical to final δ-lactones [127]. As reported, oxidative carbonylation of amines or alcohols yields ureas or carbonate esters, respectively.…”

Cooperative Polar/Steric Strategy in Achieving Site‐Selective Photocatalyzed C(sp3)−H Functionalization

“…Based on the similar but wider concept of 1,5‐radical translocation, synthetically useful methods for δ‐site‐selective C−H functionalization are now abundant. In this area, our group reported the δ‐selective C−H carbonylation of saturated alcohols leading to δ‐lactones …”

Conjugate Allylation of Cyclic α,β-Unsaturated Esters

“…5 In order to determine the relative configuration, 1,4-allylation product 11a with dr = 70:30 was submitted to ozonolysis followed by reductive workup in MeOH, CH 2 Cl 2 , and pyridine (4:4:1) giving alcohol 13, 21 which was cyclized to the lactone 14 in 65% yield (Scheme 4). Comparison of its NMR spectra with literature data 22 Due to the poor results of allylcuprate addition, only the conditions of method B and C were applied to the esters 9 and 10 with increased ring size (Scheme 5, Table 1). 19,20 The results in Table 1 reveal that for six-and seven-membered esters 9, 10 methods B and C behave somewhat complementary depending on the ester moiety.…”