Siloxyalkyne-Alkene Metathesis: Rapid Access to Highly Functionalized Enones

Abstract

The advent of structurally defined metal alkylidenes capable of promoting p-bond metathesis under mild conditions, with high efficiency and functional group compatibility, has had a profound effect on modern organic synthesis.[1] Among a range of synthetically useful transformations, the enyne metathesis is particularly noteworthy for the ability to assemble two carbon ± carbon bonds in a single step starting from appropriate alkyne and alkene components. [2] However, elaboration of the full synthetic potential of this process has been limited largely to the use of simple, unactivated enyne precursors. [3] We report here a mechanistically intriguing example of the participation of siloxyalkynes in the intramolecular Ru-catalyzed metathesis with terminal alkenes, which resulted in the development of a new method for the synthesis of highly functionalized enones III starting from readily accessible acyclic precursors I (Scheme 1). [4] Furthermore, this approach represents a novel method for the construction of silyldienol ethers II starting directly from enyne I, conceptually different from the conventional enol silylation of carbonyl compounds. Scheme 1. Projected outcome of the siloxyalkyne ± alkene metathesis.Our studies began with the preparation of a model cyclization substrate 2 (Scheme 2). Construction of siloxyalkyne 2 was accomplished according to a modified Kowalski protocol [5] entailing the initial conversion of ester 1 to the corresponding dibromoketone, followed by generation of the ynolate anion (LHMDS, nBuLi) and silylation with TIPSOTf to afford enyne 2.Scheme 2. Preparation of siloxyalkyne 2. LiHMDS lithium bis(trimethylsilyl)amide, TIPSOTf triisopropyl trifluoromethanesulfonate. We next systematically examined several olefin metathesis catalysts in order to achieve the desired conversion of siloxyalkyne 2 to the corresponding diene 3 [Eq. (1)]. Following the unsuccessful attempts to employ either the original Grubbs or the Schrock Mo-catalyst 6 [7] (Table 1, entries 1 and 2), we turned our attention to the recently developed Ru-complexes bearing highly nucleophilic imidazolylidene ligands. [8] To our delight, both 7 [9] and 8 [10] were found to promote the desired transformation, nevertheless they displayed a noticeable difference in reactivity. [11] The reaction proceeded to completion in the presence of 8 (5 mol %) over a period of 13 h at 20 8C, and within minutes at 60 8C (entries 4, 5). The cyclization employing complex 7 was [6] a) L.