摘要：Laboratory of Synthesis and NaturalProducts, Institute of Chemical Sciences and Engineering, EPFL-SB-ISICLSPN,CH-1015 Lausanne, Sw

转自：康龙化成

Oxidative Rearrangement of1,1-disubstituted Alkenes to Ketones

Qiang Feng, Qian Wang, Jieping Zhu*

Laboratory of Synthesis and NaturalProducts, Institute of Chemical Sciences and Engineering, EPFL-SB-ISICLSPN,CH-1015 Lausanne, Switzerland

—Science, 2023,379, 1363–1368.

Recommended by Shi Li_MOC

KEYWORDS:Pdcatalysis (反应类型),oxidative rearrangement (反应类型),ring expansion (反应类型),dyotropic rearrangement (反应类型), C(sp2)–O (成键类型), strained methylene cyclobutane (原料),1,1-disubstitutedalkenes (原料), ketones (产物)

ABSTRACT: TheWacker process, which is widely used to convert monosubstituted alkenes intothe corresponding methyl ketones, is thought to proceed through a Pd(II)/Pd(0)catalytic cycle involving a b-hydride elimination step. This mechanisticscenario is inapplicable to the synthesis of ketones from the 1,1-disubstitutedalkenes. Current approaches based on semi-pinacol rearrangement of Pd(II)intermediates are limited to the ring expansion of highly strained methylene cyclobutane derivatives. Herein, Zhu report asolution to this synthetic challenge by designing a Pd(II)/Pd(IV) catalyticcycle incorporating a 1,2-alkyl/Pd(IV) dyotropic rearrangement as a key step.This reaction, compatible with a broad range of functional groups, isapplicable to both linear olefins and methylene cycloalkanes, includingmacrocycles. Regioselectivity favors the migration of the more substitutedcarbon, and a strong directing effect of the b-carboxyl group was alsoobserved.

Oxidativefunctionalization of alkenes. (A)Wacker reaction of monosubstituted alkenes. The β-hydride eliminationterminates the Pd (II)/Pd (0) catalyticcycle. (B) Wacker reaction of 1.1-disubstituted terminal alkenes using Grigg’sand Wahl’s previous work on ring expansion of the methylene cyclobutanes. (C)Reaction design. A Pd(II)/Pd(V) catalytic cycle involving dyotropic orsemi-pinacol rearrangement. For comparison purposes, the Tiffeneau-Demjanov homologation of ketones involving diazonium intermediates is presented in thesame figure.

From 1,1-disubstituted alkenes torearranged ketones

Directing effect of carboxyl group

Prof. Jieping Zhu et al have developed a Pd(II)-catalyzed oxidative conversion of1,1-disubstituted alkenes to the rearranged ketones. Thereaction, applicable to both the linear terminal alkenes and the methylenecycloalkanes, is compatible with a wide range of functional groups includingalkyl halides, aryl halides, alkyl tosylate, hydroxyl, carboxylic acid, ester,lactone, amide, and ketone and α,β-unsaturatedketone, providing products with handles for further chemical transformations.

祝介平教授课题组发展了Pd(II)-催化的氧化重排过程，利用1,1-二取代烯烃实现了酮的制备。反应可以应用于线性端烯、环烯烃以及大环，并可兼容一系列不同的官能团，为进一步的分子修饰提供了可能性。此反应的发展为1,1-二取代烯烃到酮的转化提供了新的思路。

来源：新浪财经