Silyloxy-Cope Rearrangement Research Articles

Microwave-Assisted Silyloxy-Cope Rearrangement of syn-Aldol Products in DMF: Enhancement of Rate and Diastereoselectivity

Microwave-assisted Cope rearrangements of 1,5-dienes embedded in a syn-aldol structure proceed in substantially reduced reaction times and markedly increased diastereoselectivity when conducted in DMF as solvent.

An approach to the synthesis of the phomoidrides.

The phomoidrides are a structurally fascinating family of natural products which possess moderate inhibitory activity against Ras farnesyl transferase and squalene synthase. Since their discovery they have inspired a great deal of attention from synthetic chemists. Our own work, culminating in an efficient synthesis of the fully elaborated tetracyclic core of phomoidrides B and D, is described herein. The synthesis relies on a late stage tandem reaction involving a novel carbonylation reaction that delivers the strained bicyclic pseudoester system, which strain in turn drives a highly efficient silyloxy-Cope rearrangement that delivers the tetracyclic core of phomoidrides B and D. Several examples of this powerful tandem reaction are presented that document its tolerance of significant structural variation. The application of this methodology to the synthesis of a phomoidride D precursor lacking only the maleic anhydride is described, and the prospects for the completion of a total synthesis are discussed.

Highly Stereoselective and Efficient Synthesis of Functionalized Cyclohexanes with Multiple Stereocenters.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Highly stereoselective and efficient synthesis of functionalized cyclohexanes with multiple stereocenters.

Chiral 7-oxo-2-enimides 2, which were readily obtained through a silyloxy-Cope rearrangement of syn-aldol products 1, have proved to be versatile substrates for a one-step, highly efficient and stereoselective synthesis of functionalized cyclohexanes. Organocopper and organoaluminum reagents have been employed as nucleophiles that underwent a conjugate addition to the enimide structure of the Cope products. The enolates formed in situ attacked the aldehyde or iminium ion in an intramolecular aldol or Mannich reaction, respectively, to directly yield cyclohexanols 3 and 4 and cyclohexylamines 5, respectively, in moderate to good yields and with excellent stereocontrol.

Stereoconvergent palladium-catalyzed carbonylation of both E and Z isomers of a 2-trifloxy-1,3-butadiene.

[reaction: see text] Carbonylation of the illustrated Z-tetrasubstituted enol triflate followed by tandem silyloxy-Cope rearrangement leads to the CP-263, 114 core ring system with the all-carbon quaternary stereocenter intact in 46% yield. Subjection of the corresponding E isomer to the same conditions gives the same product in 56% yield. This observation is explained by a mechanism involving isomerization of a pi-allyl palladium species involving an allenic intermediate.

Novel and Stereocontrolled Synthesis of Enantiopure and Polyalkyl Substituted Piperidines

A flexible and stereodivergent synthesis of enantiopure piperidines with up to four alkyl-substituted chiral centers is reported which proceeds by way of a double nucleophilic addition of primary amines to the 7-oxo-2-enimides 1. These in turn are accessible via the silyloxy-Cope rearrangement of chiral syn-aldol products.

Stereodivergent Synthesis of Enantiopure Tetrahydropyrans via the Silyloxy-Cope Rearrangement of Chiral Aldol Products

A stereoselective synthesis of highly substituted and enantiopure tetrahydropyrans from chiral 7-hydroxy-2-alkenoic imides and esters is described. Depending on the carboxylic acid derivative the base-induced cyclization is kinetically or thermodynamically controlled to deliver either tetrahydropyran stereoisomer selectively.

Silyloxy-cope rearrangement of chiral aldol adducts

The silyloxy-Cope rearrangement of a chiral 1,5-diene generated from aldol condensation proceeds in high yield and selectivity under mild thermal conditions to generate a new stereocenter five atoms removed from the chiral auxiliary.

Lactol-regulated silyloxy-Cope rearrangement and its application to the total synthesis of dictymal, an aldehyde possessing an iridoid dimeric structure

Dictymal, a congener of epoxydictymene isolated from a brown alga, Dictyota dichotoma has been totally synthesized via a lactol-regulated oxy-Cope rearrangement of an appropriately designed dimer obtained from two C10-synthons (iridoids).

Synthetic photochemistry. Part 44. Total synthesis of ceroplastol II and albolic acid, 5-8-5-membered tricyclic sesterterpenoid insect wax constituents, via stereocontrolled silyloxy-Cope rearrangement with a normally disfavoured transition state

To a 1,5-diene, prepared by CrCl2-mediated condensation of two iridoid synthons, was appended a lactol moiety, which was subjected to a stereocontrolled silyloxy-Cope rearrangement to give, via a normally disfavoured boat transition geometry, a thermolysate, from which the total synthesis of optically active Ceroplastol II and albolic acid, 5-8-5-membered tricyclic sesterterpenoids, was accomplished for the first time.