Valentin S. Enev

Total Synthesis of Branimycin: An Evolutionary Approach

The first total synthesis of the macrolactone antibiotic branimycin (4) has been described. The key disconnection leads to a cis-dehydrodecalone core and a polyketide side chain which are connected via organometallic addition. The dehydrodecalone core was targeted via altogether five different approaches featuring various kinds of chiral elements and ring-closing methodology. In the end the most successful method starting from diepoxynaphthalene 109 was chosen to carry on with the synthesis. Thus the oxygen functions and carbon appendages were introduced via organometallic desymmetrization reactions to generate epoxy ketone 107, to which vinyl iodide 11 was added after conversion into the organolithium species. The synthesis was completed by introducing the ester side chain via Michael addition and subsequent macrolactonization.

Synthesis of 4(benzyloxymethyl)(tert.-butyl)methylsilyloxy-1,2,3-pentatriene via Brook rearrangement

Abstract The reaction of 1-lithium-3-tetrahydropyranyloxy-1-propyne with (benzyloxymethyl)-( tert. -butyl)methylsilyl methyl ketone gave rise to the corresponding α-silylated propargylic alcoholate anion, which led in a succession of Brook rearrangement and 1,4-elimination to the title compound in good yield.

Grubbs' RCM in the Total Synthesis of the Microtubule Stabilizing Drug Laulimalide

Two independent syntheses of the microtubule stabilizing antitumor agent laulimalide are described, which mainly differ with respect to the macrocyclization step. The first synthesis employs a Still–Gennari olefination and the second one an Alexakis-type, allylsilane/acetal addition to close the final ring. For the construction of the dihydropyran subunits, RCM methodology and alternative strategies are presented in comparison.

A Novel Stereoselective Reaction Cascade Leading fromα-Silylated Allylic Alcohols to Aldol-Type Products

The treatment of a-silylated allylic alcohols with epoxidizing reagents afforded in a highly stereocontrolled fashion a-silylated aldols. The transformation is proposed to proceed either by a reaction cascade involving stereospecific epoxidation of the allylic-alcohol moiety followed by an acid-supported pinacol-type rearrangement, or by a sequence consisting of a p-face-selective electrophilic attack at the allylic silane moiety with hyperconjugative stabilization of the evolving carbocation, followed by rearrangement of the thus obtained pentacoordinated silanium ion (see Scheme 3). Depending on the reaction conditions, the p-face selectivity of the oxidation step is controlled by the stereogenic C-atom or the more remote Si-center of chirality.

Improved Synthesis of Parent Fused 7-Oxanorbornenes

The synthesis of parent fused 7-oxanorbornenes 1 and 2 based on double Diels–Alder reaction of methyl propiolate with furan followed by saponification and reductive Barton decarboxylation is described.

The reaction of acylsilane-enolates with benzaldehyde: Reaction cascade leading to α-Benzoyloxy-γ-hydroxysilanes

Abstract The reaction of acylsilane-enolates with benzaldehyde gives rise to α-benzoyloxy-γ-hydroxysilanes in a reaction cascade involving aldol addition, hemiacetal formation, stereospecific intramolecular Cannizarro type disproportionation, and transesterification. This reaction pathway is supported by the separate transformation of proposed intermediates to the final products.