Modeling the Stereoselectivity of the Johnson−Claisen Rearrangements in the Danishefsky Synthesis of Gelsemine

Abstract

[reaction: see text] The stereochemistries of [3,3] sigmatropic Johnson-Claisen (J-C) rearrangements of six intermediates studied in the synthesis of gelsemine were modeled using DFT methodology. The possible origins of the rearrangement stereoselectivity are explored and compared with the experimentally suggested rationalizations by Danishefsky et al. (J. Am. Chem. Soc. 2002, 124, 9812-9824). In the intermediate used for the J-C rearrangement in the Danishefsky synthesis (3), the closure is inhibited by the repulsive interactions between the enolate terminus and the carbon atoms of the double bond as well as with the hydrogen on C7. The closure is favored by stabilizing interactions between the enolate terminus and the H's of the oxetane ring.

Claisen Rearrangement of Aliphatic Allyl Vinyl Ethers from 1912 to 2012: 100 Years of Electrophilic Catalysis

“…Complementary to the various experimental studies, computational investigations on different levels of theory have been accomplished to obtain more information about the transition structure. [9][10][11][12][31][32][33][34][35] In principle, computational chemistry is a very helpful tool as it allows a picture of the extremely short-lived (i.e., experimentally hard to get to) species of a transition state. of bond cleavage and formation in the Claisen rearrangement of the prototypical ally vinyl ether.…”

Asymmetric Total Synthesis of (+)-21-epi-Eburnamonine Via a Photocatalytic Radical Cascade Reaction

“…We envisioned that the known compound propynal 15 [32] would be an appropriate precursor for construction the A/B/C/D framework of eburnane skeleton through intra-intramolecular photocatalytic radical cascade reaction. The resultant tetracyclic product 14 bears a propenol functionality at C20, which allows us to forge the C20 all-carbon quaternary stereocenter of 13 via Johnson-Claisen rearrangement [62,[69][70][71][72]. We supposed that the substrate-controlled stereoselectivity in the rearrangement process could guarantee the desired C20 (S) configuration.…”

Computational organic chemistry

“…Density functional theory has now been used to investigate the observed stereochemistry of this reaction. 49 It was found that repulsive interactions occurred in the transition structure for the unobserved reaction, while stabilising interactions occurred in the transition structure for the observed reaction. Thus a perfect agreement with experiment was obtained.…”