Origins of Stereoselectivity in Strain‐Release Allylations

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

“…When this protocol was employed to generate and react (without isolation) crotylsilane 23 with 9a , however, we were surprised to find that the reaction produced, at best, trace amounts of the desired product. Based on a computational model for the first-generation crotylsilylation reaction 42 and on Evans’ comprehensive model for merged 1,2- and 1,3-stereoinduction in related aldol reactions 43 , we constructed transition state model A for the successful reaction of first-generation crotylsilane 20 , and then applied it to the reaction of crotylsilane 23 to construct transition state model B . This exercise revealed that the tethering of the phenol to the silane with diaminophenol ligand 22 , which induces the greater reactivity in the silane, also has the unintended consequence of generating a prohibitive steric interaction between the t -Bu group on the phenol ring and the β-OTES group on the aldehyde.…”

A new and more powerfully activating diamine for practical and scalable enantioselective aldehyde crotylsilylation reactions

“…Whereas the oxygen in 3 is free to rotate and dynamically interact with both Si-N antibonding orbitals, however, the oxygen in 8 is not, and though the differences are small, the shorter O-Si bond distance and larger C3-O-Si bond angle in 3 are consistent with greater O to Si π-type donation and therefore reduced silane acidity. Transition state effects are almost certainly relevant as well, 18 and as the geometry around Si changes along the reaction coordinate for the allylsilylation reaction, the phenoxy group in 3 is more free to rotate than is the phenoxy group in 8 . This freer rotation insures that the O to Si π-type donation – and therefore the minimization of the acidity of the silicon center – can be maintained throughout the allylsilylation reaction more fully in 3 than in 8 .…”

Strategies and Methods for the Synthesis of Anticancer Natural Product Neopeltolide and its Analogs

“…[12] As summarized in Scheme 3, starting from aldehyde 26 , which was synthesized from Noyori asymmetric hydrogenation followed by DIBAL-H reduction, a Leighton asymmetric allylation[13] was used to synthesize compound 28 with the C 11 stereocenter. After 28 was converted to α,β-unsaturated thioester 29 , a Feringa-Minnaard reaction enabled the introduction of the C 9 methyl group in a stereoselective manner.…”