Catalytic Anti-Markovnikov Transformations of Hindered Terminal Alkenes Enabled by Aldehyde-Selective Wacker-Type Oxidation

Abstract

A new strategy for the functionalization of sterically hindered terminal olefins is reported. Alkenes bearing quaternary carbons at the allylic or homoallylic position are readily oxidized to the corresponding aldehydes by palladium/copper/nitrite catalysis. A broad range of functional groups including esters, nitriles, silyl ethers, vinylogous esters, ketones, lactones, and β-ketoesters are tolerated under the reaction conditions. The crude aldehyde products can be transformed further, enabling direct conversion of hindered terminal alkenes to various other synthetically useful functional groups, resulting in formal anti-Markovnikov hydroamination, among other transformations.

Nickel-catalyzed enantioselective allylic alkylation of lactones and lactams with unactivated allylic alcohols

“…Reduction of lactam 5aa with lithium aluminium hydride delivers chiral piperidine derivative 9 , which is of potential value to medicinal chemists. 9 Use of the aldehyde selective Wacker procedure 19 affords aldehyde 10 in 75% yield. Lastly, cleavage of the benzoyl protecting group under basic conditions provides unprotected lactam 11 in 84% yield.…”

Palladium-Catalyzed Anti-Markovnikov Oxidation of Aromatic and Aliphatic Alkenes to Terminal Acetals and Aldehydes

“…An efficient PdCl 2 (PhCN) 2 /CuCl 2 /AgNO 2 /O 2 catalytic system was reported by Grubbs et al, 24,57 which provided aldehydes in up to 70% yield and with up to 90% AM selectivity (Scheme 25). The proposed key intermediate involves a NO 2 radical acting as a ligand for Pd, and the NO 2 radical attacks at the terminal carbon of the alkene.…”

Synthesis of α‐Quaternary Aldehydes via a Stereoselective Semi‐Pinacol Rearrangement of Optically Active Epoxy Alcohols

“…After the oxidation of 8 to aldehyde 9 , the reaction with phenylmagnesium bromide and a subsequent DMP oxidation afforded ketone 10 (66% yield over three steps). A Wacker‐type oxidation of the olefin moiety in 10 provided aldehyde 11 , which was ultimately converted into serotonin antagonist 7 upon a reductive amination . We also achieved the formal synthesis of ent ‐ 7 by the transformation of 1 a into ent ‐ 9 .…”