Enantioselective reactions of crotyl silane with ortho-quinone methide intermediates and progress toward an asymmetric cyclopropanation of allenylsilanes
Wong, Christopher Ryan
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The unique ability of allyl and crotyl silane reagents to act as competent nucleophiles as well as electron-rich dienophiles prompted an investigation into utilizing allyl and crotyl silanes in reactions with ortho-quinone methides (oQMs). In the presence of anhydrous FeCl3 and 2,6-lutidine, reaction of allyltrimethylsilane and the oQM intermediate generated from 2-(hydroxy(phenyl)methyl) phenol was found to produce both the cycloaddition and 1,4-addition product in 92% combined overall yield. This method was successfully extended to a stereoselective reaction between an enantioenriched (S,E)-crotyl silane and a variety of oQMs generated from electronically diverse ortho-hydroxybenzyl alcohol precursors. Both the chiral chroman and crotylation products were isolated in ratios reflective of the electronic nature of the parent oQM with overall combined yields of up to 96% and >99:1 er. A titanium tetrachloride-mediated ring-opening and elimination sequence was subsequently developed to provide direct access to the crotylation products, containing a unique vicinal tertiary carbon stereocenter bond construction, in good yields and enantioselectivities. An enantioselective cyclopropanation of di- and tri-substituted allenylsilanes was investigated to expand the relatively limited scope of asymmetric allene cyclopropanation reactions and to provide access to functionalized, chiral alkylidenecyclopropanes (ACPs). In the presence of 2 mol% of the Ru(S-Pheox) catalyst, 1,1-di-substituted allenylsilanes reacted with the metal carbenoid generated from benzyl diazoacetate ester to give the corresponding ACP products in up to 85% yield and 99:1 er. Increasing the catalyst loading to 10 mol% enabled the first reported asymmetric cyclopropanation of chiral, tri-substituted allenylsilanes, which gave optimal yields for the (R)-allenylsilanes over the corresponding (S)-isomers. A proposed mechanistic model was devised to rationalize the observed double stereodifferentiation event in the asymmetric cyclopropanation, which predicted the (R)-allenylsilanes and (S)-pheox ligand to be a matched pair. The reactivity of the densely functionalized ACP products was tested and led to the preparation of an unexpected 3-oxabicyclo[3.1.0]hexan-2-one product via iodolactonization.