Organic Chemistry Portal

Abstracts

Search:

Chemoselective Ketone Synthesis by the Addition of Organometallics to N-Acylazetidines

Chengwei Liu, Marcel Achtenhagen and Michal Szostak*

*Department of Chemistry, Rutgers University, 73 Warren Street, Newark, New Jersey 07102, United States, Email: michal.szostakrutgers.edu

C. Liu, M. Achtenhagen, M. Szostak, Org. Lett., 2016, 18, 2375-2378.

DOI: 10.1021/acs.orglett.6b00842


see article for more reactions

Abstract

N-acylazetidines are bench-stable, readily available amide acylating reagents, in which the reactivity is controlled by amide pyramidalization and strain of the four-membered ring. A general and highly chemoselective synthesis of ketones by the addition of organometallics to N-acylazetidines via stable tetrahedral intermediates offers wide substrate scope and exquisite selectivity for the ketone products.

see article for more examples



General Procedure for Ketone Synthesis from Azetidinyl Amides

An oven-dried vial equipped with a stir bar was charged with an N-acylazetidine substrate (typically, 0.50 mmol, 1.0 equiv), placed under a positive pressure of nitrogen, and subjected to three evacuation/backfilling cycles. Tetrahydrofuran (typically, 5.0 mL, 0.10 M) was added, the reaction mixture was cooled to 0 C or -78 C, followed by dropwise addition of an organometallic reagent (typically, 3.0 equiv) with vigorous stirring. After the indicated time, the reaction was quenched by slow addition of HCl (1.0 N, 5 mL), extracted with Et2O (2 x 30 mL), organic layers were combined, dried, filtered and concentrated. The sample was analyzed by 1H NMR (CDCl3, 500 MHz) and GC-MS to obtain selectivity, conversion and yield using internal standard and comparison with authentic samples. Purification by chromatography on silica gel afforded the title product.

Note: For reactions that were run at -78 C, the reaction was quenched with HCl (1.0 N, 5 mL) at -78 C and then allowed to reach room temperature. All other reactions were quenched with HCl (1.0 N, 5 mL) at room temperature. For the addition of the reactive organometallic reagents, the rate of addition was about 1 drop every 3 seconds (MeLi, n-BuLi, t-BuLi). For the less reactive organometallic reagents, the rate of addition was about 1 drop every second.


Key Words

ketones, aryl ketones


ID: J54-Y2016