A Highly Regio‐ and Stereoselective Vinylogous Horner–Wadsworth–Emmons Route to Densely Substituted 1,3‐Butadienes

Abstract

Since the landmark reports [1] by Wittig and co-workers in the early 1950s, the Wittig reaction has established itself as a gold standard for the olefination of carbonyl groups. Its efficacy was further elevated by employing phosphoryl-stabilized carbanions, in a modification known as the Horner-Wadsworth-Emmons (HWE) [2, 3] reaction. In 1935, Fuson [4] formulated the principle of vinylogy to provide a better understanding of the "anomalous" reactivity of some unsaturated compounds. Since then, this concept has been applied in many important CÀC bond-forming reactions [5] to extend the electrophilic or nucleophilic character of a functional group. Allylic phosphonium and phosphoryl ylides should in principle undergo a vinylogous Wittig/HWE reaction to give a new type of olefinic product that is regioisomerically different from that expected from the normal reaction course (Scheme 1).Aldehydes and ketones usually react preferentially at the a position of allylic phosphorus ylides.[6] However, a few examples have been reported [7][8][9] in which, in spite of preferential reaction at the g position, no vinylogous Wittig/ HWE olefination products were formed. Corey and Erickson [10] reported a single example of a vinylogous Wittig reaction of (E)-3-methoxycarbonyl-2-methylallyltriphenylphosphonium bromide with hexanal under special conditions to give a stereoisomeric mixture of g-condensed vinylogous products. It appears that the base used, the olefin geometry, and the substituents present were crucial to the success of this reaction. In contrast, the analogous trans phosphonate provided only the a-condensed HWE product. [10,11] Although there has been tremendous growth in the chemistry of allylic phosphorus ylides, [12] to our knowledge there has been no other report of a vinylogous Wittig or related reaction.We speculated that for a vinylogous Wittig/HWE reaction to occur, three essential requirements should be fulfilled: 1) selective reaction of the ylide at the g carbon atom, 2) selective isomerization of the vinyl phosphorus derivative 2 (Scheme 1) to the allyl phosphorus derivative 3, and 3) the substituent Y should be able to modulate the reactivity of the phosphorus center and ensure rapid equilibration to facilitate the cycloelimination. A potential solution to these requirements might accrue from the application of our recently developed [13,14] sulfonium methylide [15] chemistry with suitably substituted vinyl phosphonates. Herein we present a highly regio-and stereoselective vinylogous HWE reaction [16] of aldehydes with allylic phosphonates generated in situ from a-cyano vinyl phosphonates.The vinyl phosphonates 7 a-c were prepared by a known method.[17] When 7 a was added to a mixture of sodium dimsylate and Me 3 SI, and the intermediate was quenched with benzaldehyde, the 1,3-diene 5 a was formed along with a trace amount of the HWE product 6 a (method A). Diene 5 a must have been produced via the allylic ylide 1 a through a vinylogous HWE reaction (Scheme 2). The product was formed in moderate (ca. 4...