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Synthesis of Cembranoid Analogues through Ring‐Closing Metathesis of Terpenoid Precursors: A Challenge Regarding Ring‐Size Selectivity
Author(s) -
Heidt Tanja,
Baro Angelika,
Köhn Andreas,
Laschat Sabine
Publication year - 2015
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201502051
Subject(s) - metathesis , chemistry , ring closing metathesis , stereochemistry , terpenoid , alkyl , double bond , ring size , selectivity , functional group , salt metathesis reaction , ring (chemistry) , catalysis , organic chemistry , polymerization , polymer
A systematic study on ring‐closing metathesis with Grubbs II catalyst to cembranoid macrocycles is described. Acyclic terpenoids with a functional group X in the homoallylic position relative to an RCM active terminus and substituents R, R 1 directly attached to the other terminal double bond were prepared from geraniol derived trienes and fragments that are based on bromoalkenes and dimethyl malonate. Such terpenoids were suitable precursors, despite the presence of competing double bonds in their framework. The size of R and R 1 is crucial for successful macrocyclization. Whereas small alkyl substituents at the double bond directed the RCM towards six‐membered ring formation, cross metathesis leading to dimers dominated for bulkier alkyl groups. A similar result was obtained for precursors without functional group X. In the case of unsymmetrically substituted terpenoid precursor (R=Et, R 1 =Me) with homoallylic OTBS or OMe group, the RCM could be controlled towards formation of macrocyclic cembranoids, which were isolated with excellent E ‐selectivity. The role of the substituents was further studied by quantum chemical calculations of simplified model substrates. Based on these results a mechanistic rationale is proposed.