Formal Asymmetric (4+1) Annulation Reaction between Sulfur Ylides and 1,3‐Dienes

Abstract

A highly enantioselective synthesis of functionalized cyclopentanoids by a formal asymmetric (4+1) annulation strategy was developed. The methodology consists of a stereoselective cyclopropanation reaction between chiral sulfur ylides and 1,3-dienes followed by a, in situ, stereospecific MgI2 -catalyzed rearrangement of vinylcyclopropanes. This method is distinguished by a remarkable compatibility with functional groups and a high stereocontrol.

Synthesis of Vinylcyclopropane‐Fused Pyrazolone Derivatives by Sulfur Ylide‐Initiated 1,6‐Michael Addition‐Cyclization Reactions

“…We hypothesize that 3a is transformed to 5 via the following reaction mechanism, which is consistent with the pioneering work of Robiette's group (Scheme ) . Highly diastereoselective rearrangement of vinylcyclopropane‐fused pyrazolone to spiro‐cyclopentene pyrazolone takes place in the presence of MgI 2 via a ring‐opening step.…”

“…This likely reflects the fact that remote 1,6‐addition/substitution cyclization is much more difficult than 1,2‐ or 1,4‐addition annulation, in part because of the need to ensure regioselectivity between the β‐ and δ‐positions due to the propagation of electronic effects through the conjugated π‐system . Robiette and colleagues were the first to present an effective [2+1] annulation between sulfur ylides and linear α,β,γ,δ‐unsaturated esters, affording versatile vinylcyclopropane intermediates that could be transformed to functionalized cyclopentanoids in one pot . This reaction shows limitations in substrate compatibility and efficiency, highlighting the need for more efficient methods for remote cyclization of ylide chemistry.…”

Synthesis of 1-Acyl-2-vinylcyclopropanes: Utilizing Copper-Carbenoid versus Sulfur Ylide Methodology

“…the amount of 13 was increased to 11 equivalents following a method described by Rousseau. 22 However, the yield of 6a•Br decreased to 43% (Table 2, entry 2). When the respective allylic bromide 11a was treated with 3 equivalents of 13 in acetone instead of CH 2 Cl 2 , based on a protocol reported by La Rochelle, 23 the reaction indeed was complete after 24 hours affording 6a•Br in 92% yield (Table 2, entry 3).…”

Asymmetric Synthesis of 2,3‐Dihydrobenzofurans by a [4+1] Annulation Between Ammonium Ylides and In Situ Generated o‐Quinone Methides

“…Following our recent research focused on ammonium ylide mediated asymmetric annulation reactions and [4+1] annulations using ylides, we became interested in testing the potential of in situ generated achiral and chiral ammonium ylides (by starting from ammonium salts 6 ) to access 2,3‐dihydrobenzofurans with control of both the relative and the absolute configuration. Besides the development of the first (highly) asymmetric ammonium ylide based protocol, which will overcome the less than satisfactory enantioselectivity observed so far when using chiral sulfur ylides, we also became interested in investigating this reaction in more detail by computational means to reveal the key factors in this ylide‐mediated [4+1] annulation reaction…”