Intramolecularly Competitive Ireland-Claisen Rearrangements:  Scope and Potential Applications to Natural Product Synthesis

Abstract

A variety of bis-allylic esters were prepared by vinylmetal addition to cycloalkenones followed by esterification either in situ or in a separate operation. For chiral cyclohexenones, the vinyl additions generally occurred with >10:1 diastereoselectivity. Although in some cases the bis-allylic esters proved to be sensitive to silica gel or other adsorbents, all of the esters examined could be isolated in acceptable purity. The Ireland-Claisen rearrangement of the bis-allylic esters occurred with complete regioselectivity via the exocyclic alkene. The alkene stereochemistry and the stereochemistry at C-2 and C-3 of the pentenoic acid products were consistent with a chairlike transition state in the rearrangement. Substituents at the carbons adjacent to the allylic carbinol carbon (i.e., C-2 or C-6 in cyclohexenone-derived substrates) directed the stereochemical course of the rearrangement. The rearrangements generally proceeded so as to place the larger of the C-2 or C-6 substituents in the pseudoequatorial position with respect to the chairlike transition state. For a bis-allylic ester bearing both a C-2-CH(3) and a C-6-OMEM substituent, the rearrangement product resulted from the nominally smaller OMEM substituent occupying a pseudoequatorial position with respect to the chairlike transition state.

Synthesis of 1,2‐Amino Alcohols by Sigmatropic Rearrangements of 3‐(N‐Tosylamino)allylic Alcohol Derivatives

“…[33] However, these latter conditions have been routinely used in glycolate-Ireland-Claisen rearrangements with no adverse effect on the diastereoselectivity. [13,34] By starting from a purified glycolate 22 and reducing the amount of base and TMSCl (2 equiv each) the diastereomeric ratio was not altered.…”

“…As enolization of 22 was carried out in the presence of an excess of KHMDS and TMSCl, post-enolization of the rearranged a-alkoxy-b-amino esters trimethylsilyloxyester could not be ruled out to account for the low diastereoselectivity. [33] However, these latter conditions have been routinely used in glycolate-Ireland-Claisen rearrangements with no adverse effect on the diastereoselectivity. [13,34] By starting from a purified glycolate 22 and reducing the amount of base and TMSCl (2 equiv each) the diastereomeric ratio was not altered.…”

Directed Hydrogenations and an Ireland–Claisen Rearrangement Linked to Evans–Tishchenko Chemistry: The Highly Efficient Total Synthesis of the Marine Cyclodepsipeptide Doliculide

“…Reaction of 27 with TBSOTf then produced TBS ether 23 as the substrate for the crucial Ireland–Claisen rearrangement. After a series of unsuccessful attempts to induce the rearrangement by treatment with TBSCl/LDA or TMSCl/LDA in THF/HMPA29, 30 at temperatures between −78 °C and up to 60 °C, the difficulties with the reaction could be overcome by the use of KHMDS and TBSOTf in Et 2 O/THF 35. This reagent/solvent combination induced clean rearrangement of 23 and, after the in situ cleavage of the TBS‐ester/TBS‐ether groups with HF ⋅ pyridine, gave acid 28 as a single isomer in a remarkable overall yield of 85 %.…”

“…Eur.J.2015, 21,8403 -8407 www.chemeurj.org THF/HMPA [29,30] at temperatures between À78 8Ca nd up to 60 8C, the difficulties with the reactionc ould be overcome by the use of KHMDS and TBSOTf in Et 2 O/ THF. [35] This reagent/solvent combination induced clean rearrangement of 23 and, after the in situ cleavage of the TBS-ester/TBS-ether groups with HF·pyridine, gave acid 28 as as ingle isomer in ar emarkable overall yield of 85 %.…”

Synthesis of the C21–C34 fragment of antascomicin B

“…The HOAc served to protonate excess base and prevent enolization of the rearrangement product. 17 The rearrangement presumably proceeded via a chair-like transition state corresponding to Z -ketene acetal 5 ′ in which the larger OTBS-substituted C30 carbon was oriented in the pseudo-equatorial position. Pentenoic acid 4 was obtained in very good yield as a single diastereomer based on 1 H NMR and 13 C NMR analyses.…”