Stereoselective Construction of Cyclic Ethers via Intramolecular Acyl Radical Cyclizations:  A Practical Solution to Decarbonylation

Abstract

Cyclic ether containing natural products represent important synthetic targets owing to their unique structural and biological properties. 1 The development of new methodology for the synthesis of this ubiquitous class of compounds has been the focus of extensive investigation for the last 20 years. However, the development of new and general methods capable of accessing this class of compounds continues to dominate this area of investigation. 2 A number of radical methods 3-5 have recently been developed for the stereoselective synthesis of cyclic ethers. Methods that utilize acyl radicals 6 have, however, not been forthcoming. In this paper, we describe the first example of the intramolecular addition of an acyl radical to a vinylogous carbonate for the efficient and stereoselective construction of 5-, 6-, and 7-membered cyclic ethers (eq 1). 7

Chemistry of Acyl Radicals

“…The selectivity is explained in the standard manner through the intervention of a Beckwith, chairlike transition state. Related examples in which the SO 2 Ph group was replaced by CO 2 Me behaved similarly. ,

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Ultrasonographic findings in conservatively treated placenta percreta

“…The literature shows that this process depends on the stability of the corresponding alkyl radicals, on the temperature, and on the solvent used 1. 15, 16 Decarbonylation is known to be decreased to some extent when using (Me 3 Si) 3 SiH/Et 3 B as radical initiators17 and more effectively through an indirect approach recently proposed by Skrydstrup and co‐workers through SmI 2 reduction of different radical precursors ( N ‐acyl oxazolidinones) at temperatures below −40 °C 18. In principle, the simple approach of lowering the temperature is suited to aldehydes owing to the lower activation energy of acylation versus the decarbonylation reaction 19.…”

Tin-Free Radical Reactions Mediated by Organoboron Compounds

“…By using Et 3 B/O 2 initiation rather than AIBN, the cis-oxepanones are obtained in higher stereoselectivity and yield since the decarbonylation of the intermediate acyl radical is suppressed (Scheme 3, Eq. 3a) [11]. In another striking example, a thermally unstable propargyl bromide cobalt complex cyclizes in the presence of Ph 2 SiH 2 under Et 3 B/O 2 initiation at 20 • C. A mixture of reduced and bromine atom transfer products are isolated (Eq.…”