Direct, Mild, and General n-Bu₄NBr-Catalyzed Aldehyde Allylsilylation with Allyl Chlorides

Abstract

A direct, mild, and general method for the enantioselective allylsilylation of aldehydes with allyl chlorides is reported. The reactions are effectively catalyzed by 5 mol% of n-Bu4NBr, and this rate acceleration allows the use of complex allyl donors in fragment-coupling reactions and of electron-deficient allyl donors. The results are 1) significant progress toward a “universal” asymmetric aldehyde allylation reaction that can reliably and highly stereoselectively couple any allyl chloride-aldehyde combination, and 2) the discovery of a novel mode of nucleophilic catalysis for aldehyde allylsilylation reactions.

A Catalytic Dual Isomerization/Allylboration Sequence for the Stereoselective Construction of Congested Secondary Homoallylic Alcohols

“…Quite unexpectedly, with 3g , a homoprenyl-substituted homoallylboronate, the sequential process furnished quasi-exclusively syn - 6ag with excellent enantioselectivity (19:1 dr, 90% ee). Almost identical catalytic performances were achieved when the allylic alcohol was varied ( syn - 6bg : 10:1 dr, 85% ee; syn - 6ig : 10:1 dr, 86% ee) . To gain insight into the origin of these contrasting results, three independent dual isomerizations using 1a in conjunction with either 3b , 3d , or 3g were conducted under conditions identical to those developed for the first step of the corresponding sequential process.…”

Design and 22-step synthesis of highly potent D-ring modified and linker-equipped analogs of spongistatin 1

“…This impasse inspired a search for ways to accelerate these reactions and this led to the discovery that weakly coordinating anions (e.g. Br − , I − , TfO − ) are effective catalysts that operate, the evidence suggests, by adding to the allylsilane and accessing small equilibrium concentrations of the more highly activated allylsilicate 54 . When the coupling of 13 and 11 was repeated in the presence of 20 mol% n -Bu 4 NBr, the desired product 39 was produced as a single diastereomer (≥20:1 dr) in 71% yield (94% based on recovered allylchloride 13 ), presumably through the intermediacy of the activated allylsilicate 38• Br − .…”

Successive Nucleophilic and Electrophilic Allylation for the Catalytic Enantioselective Synthesis of 2,4-Disubstituted Pyrrolidines

“…Based on this reactivity pattern, we envisioned an approach to N -protected 2,4-disubstituted pyrrolidines wherein the bis -Boc-carbonate derived from 2-methylene-1,3-propane diol is subjected to successive nucleophilic and electrophilic allylation (Figure ). , While numerous related bifunctional allylmetal reagents based on tin, boron, or silicon have been described, the use of such reagents for pyrrolidine synthesis is uncommon and is only known in the context of Trost’s pioneering work on imine-mediated trimethylenemethane (TMM) cycloadditions. ,, Catalytic enantioselective cycloadditions of this type have been reported using phosphoramidite-modified palladium catalysts. − However, while high enantioselectivities are observed in TMM cycloadditions of aryl-substituted imines, , the construction of 2-alkyl-4-methylenepyrrolidines in highly enantiomerically enriched form remains a largely unmet challenge. Here, utilizing an iridium catalyst modified by an inexpensive, commercially available ligand, SEGPHOS, we report a catalytic protocol for the synthesis of diverse 2-substituted-4-methylenepyrrolidines, including 2-alkyl derivatives, that avoids the use of moisture-sensitive imine reactants.…”