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Setting the Bridgehead Oxidation Level in trans ‐Tricyclo[9.3.1.0 3,8 ]pentadecanes as a Prelude to the Dual Synthesis of Taxol and Taxusin
Author(s) -
Paquette Leo A.,
Combrink Keith D.,
Elmore Steven W.,
Zhao Mangzhu
Publication year - 1992
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/hlca.19920750604
Subject(s) - chemistry , pinacol , stereochemistry , stereospecificity , stereoselectivity , ketone , ring (chemistry) , diketone , catalysis , organic chemistry
The key elements associated with the synthetic elaboration of functionalized trans ‐tricyclo‐[9.3.1.0 3,8 ]pentadecanes carrying either a bridgehead H or OH substituent are detailed. Starting with 12 , a ketone available in two steps from ( R )‐2‐oxo‐7,7‐dimethyl‐l‐vinylbicyclo[2.2.1]heptane, it proved possible to introduce trans ‐B/C ring juncture configuration as in 16 in five steps. This advanced intermediate constitutes the point of bifurcation. The pathway to taxusin precursor 23 was attained by stereospecific osmylation, reduction, and pinacol‐like 1,2‐ Wagner ‐ Meerwein rearrangement within acetoxy mesylate 22c. Still more abbreviated is the route to 32 , which again takes advantage of the osmylation step but proceeds, forward without reduction of the rear carbonyl group. Once hydroxy diketone 31 is produced, equilibration in the presence of ( t ‐BuO) 3 Al results in complete conversion to 32 . The many stereoselective transformations developed in the course of this study, in combination with the several thermodynamic questions that have been clarified, are expected to be highly serviceable as more advanced thrusts toward taxusin and taxol are mounted.