Asymmetric Total Syntheses of (+)-3-(Z)-Laureatin and (+)-3-(Z)-Isolaureatin by “Lone Pair−Lone Pair Interaction-Controlled” Isomerization

Abstract

The first asymmetric total syntheses of the dihalogenated medium-sized dioxabicyclic marine natural products (+)-3-(Z)-isolaureatin (1) and (+)-3-(Z)-laureatin (2) have been accomplished. Notable features of the highly stereo-, regio-, and chemoselective syntheses of these alpha,alpha'-trans-oxocene natural products include an intramolecular amide enolate alkylation to construct the alpha,alpha'-cis-oxocene, novel "lone pair-lone pair interaction-controlled" epimerizations to the alpha,alpha'-trans-oxocenes, various strategies for stereoselective introduction of halogen atoms, and novel olefin cross-metatheses for construction of the (Z)-enyne systems.

Synthesis of (+)‐Obtusenyne

“…enolate hydroxylation) we are currently unable to predict the catalyst dependence and general selectivity of the hydrosilation reactions (most probably due to the highly complex nature of the system); furthermore, we are unable to rationalize the substrate-dependent nature of the success of both the cuprate displacement reactions and the halogenation reactions. [74] The chemistry of medium-ring ether synthesis is both challenging and exciting and this work highlights some of the interesting reactivity displayed by medium-ring oxygen heterocycles in addition to demonstrating the limits of current synthetic methodology towards the synthesis of this class of natural products.…”

Oxetanes as versatile building blocks in the total synthesis of natural products: An overview

“…Three approaches have been described the total synthesis of Laureatin [66][67][68]. Suzuki and his co-workers were reported the first total synthesis of Laureatin based on biosynthesis pathway which was proposed by Murai's group [69][70][71] as shown in Scheme 11.…”

Intramolecular Enolate Alkylation: From Steroids through Cladiellins to Isolaurallene

“…Our IAEA methodology has not so far been well-suited for the synthesis of α,α′-trans-disubstituted compounds. 37 The Evans asymmetric alkylation/RCM strategy, however, has become established as a successful protocol for the construction of medium-ring oxacyclic skeletons, both α,α′-cis-and α,α′-trans-disubstituted, as illustrated with oxocenes in Scheme 29. We had been successful at exploiting the versatility of the α-alkoxy-substituted N,N-dimethylamide functionality and the substrate-controlled strategy, and thus we asked ourselves whether we could synthesize α,α′-syn-or α,α′-anti-disubstituted RCM substrates specifically without recourse to a chiral auxiliary.…”