Stereoselective oxacyclizations

McDonald and co-workers have published a partial synthesis of thyrsiferol (1) and venustatriol (2) [30]. They focused upon the regio-and stereoselective oxacyclizations [57] to approach the ABC framework, a structural feature that is common to both natural products. 

Advances in applying these studies to stereoselective oxacycle synthesis have been critically dependent upon the development of enantioselective epoxidation methods. Extensive research into designing these reactions has resulted in a wide range of structurally distinct epoxides being available in enantiomerically pure form through experimentally facile methods that utilize easily accessible catalysts. These enabling methods assure that substrate synthesis will not limit further exploration in epoxide-based cyclization reaction development. 

Boron trifluoride etherate promotes the fWt/a-selcctivc oxacyclization of polyepoxides derived from various acyclic terpenoid polyalkenes, including geraniol, farnesol, and geranylgeraniol, providing an efficient and stereoselective synthesis of substituted oxepanes and fused polyoxepanes. The oxacyclization transformations may mimic ringforming steps in the biosynthesis of trans-syn-trans-fused polycyclic ether marine natural products <2002JOC2515>. 

Acyl radical cyclization of ) -alkoxyacrylates provides five-, six-, and seven-mem bered oxacyclic ketones with high stereoselectivity [45], In a key step in the synthesis of (—)-kumausallene (55) by Evans, the tetrahydrofuran-3-one 69 was obtained stereoselectively from the acyl selenide 68 [46] (Scheme 24). 

Stereoselective hydrogen transfer reactions on oxacyclic radical intermediates are useful as shown in the synthesis of lauthisan (32) [126]. A key step in the total synthesis of brevetoxin B by Nicolaou [127] (Scheme 65) features conversion of the hydroxy dithioketal 189 into the oxoeene system 190 via cyclic hemithioketal formation and stereoselective radical-mediated desulfurization. More recently, Tachi-bana employed the same reaction sequence in the partial synthesis of ciguatoxin ]128]. 

The intermediates 2 smoothly cyclize with high regio- and stereoselectivity through reaction with the 7C-nucleophile in the alkoxy substituent. Equation 2>5 show several examples of this reaction, which in some cases (eq 3) proceeds with remarkable stereochemistry cis addition to an olefinic double bond), probably caused by an accompanying cationic oxa-Cope rearrangement. The products, oxacyclic carboxylic esters with unusual structures, may have interesting synthetic applications. 

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