[2,3]-Wittig Rearrangement as a Formal Asymmetric Alkylation of α-Branched Ketones

Abstract

The enantioselective [2,3]-Wittig rearrangement of cinnamyl­oxycyclo­pentanone derivatives was performed in the presence of a Cinchona-based primary amine. The described method provides synthetically valuable α-hydroxy ketones with quaternary stereogenic centers in excellent enantiomeric purities. Relying on the X-ray crystal structure of the product and the DFT calculations, we propose that the rearrangement is promoted by an intramolecular hydrogen bond between the substrate and the catalyst.

Asymmetric Organocatalytic [2,3]‐Wittig Rearrangement of Cyclohexanone Derivatives

“…An experiment with cinnamyloxycyclopentanone 3k proved that the optimized conditions are not optimal for other ring sizes and the results were not improved over those our previous publication (yield 71 %; dr 3.9 : 1; ee 95 %/18 %). [13] The sixmembered substrate possesses less ring-strain compared to the five-membered and, thus, is more conformationally flexible. Finally, limitations of scope were revealed.…”

“…The absolute configuration of the major diastereoisomer of the [2,3]-Wittig rearrangement product 4 a was determined by a comparison of the chiral HPLC chromatogram with the data published previously by us. [13] It is assumed that the main enantiomer is a syn-isomer with an (R,R)-configuration of stereogenic centers. The configurations of other compounds in the series were assigned by analogy.…”

“…General remarks. Full assignment of 1 H and 13 C chemical shifts is based on the 1D and 2D FT NMR spectra measured on a Bruker Avance III 400 MHz instrument, unless note. Residual solvent signals were used (CDCl 3 δ = 7.26 ( 1 H NMR), 77.16 ( 13 C NMR)) as internal standards.…”

“…[10] Our group previously reported an asymmetric [2,3]-Wittig rearrangement of oxindole, malonate and cyclopentanone derivatives, in addition to an example of a diastereoselective [2,3]-sigmatropic rearrangement of N-allyl ammonium ylides. [11][12][13][14] In 2006, Gaunt et al described the first asymmetric organocatalytic rearrangement on aliphatic cinnamyloxyketones. [15] Almost a decade later, Denmark obtained moderate results using phase-transfer catalysis on allyloxy oxindole derivatives (ee up to 54 %).…”

“…[18] We recently described a Wittig rearrangement of cyclic ketones as a method for the formal asymmetric alkylation of αbranched ketones. [13] The rearrangement of cinnamyloxycyclopentanones was performed in the presence of a Cinchona amine derived catalyst and the rearranged products were obtained in very good results (dr up to 5.2 : 1; ee up to 95 %/ 18 %). However, the method developed for the substituted cyclopentanones was incompatible with the corresponding cyclohexanone derivatives affording products in low dr and ee (dr 1.8 : 1; ee 49 %/8 %).…”