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Highly (≥98%) Stereo‐ and Regioselective Trisubstituted Alkene Synthesis of Wide Applicability via 1‐Halo‐1‐alkyne Hydro‐ boration–Tandem Negishi–Suzuki Coupling or Organoborate Migratory Insertion
Author(s) -
Xu Shiqing,
Lee ChingTien,
Rao Honghua,
Negishi Eiichi
Publication year - 2011
Publication title -
advanced synthesis and catalysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.541
H-Index - 155
eISSN - 1615-4169
pISSN - 1615-4150
DOI - 10.1002/adsc.201100420
Subject(s) - chemistry , alkene , negishi coupling , regioselectivity , alkyne , suzuki reaction , tandem , combinatorial chemistry , sonogashira coupling , propargyl , reagent , aryl , organic chemistry , palladium , catalysis , alkyl , materials science , composite material
Abstract ( Z )‐1‐Halo‐1‐alkenylboranes ( 7 ), preparable in 80–90% yields as ≥98% isomerically pure compounds via hydroboration of 1‐halo‐1‐alkynes, have been converted to a wide range of trisubstituted alkenes via three different routes in the tail‐to‐head ( T ‐to‐ H ) direction, i.e., (i) palladium‐catalyzed Negishi–Suzuki tandem alkenylation, (ii) treatment with organolithium or Grignard reagents to generate α‐bromo‐1‐alkenylboronate complexes that can undergo migratory insertion of a carbon group (R 2 ) to form ( E )‐alkenylboranes with inversion of alkene configuration (≥98% inversion), followed by fluoride‐promoted Suzuki alkenylation, and (iii) Negishi coupling to generate ( Z )‐alkenylboranes in ≥98% retention of configuration, followed by treatment with organolithium or Grignard reagents to produce trisubstituted alkenes with reversed stereo configurations. The synthetic utility of the present methodology has been demonstrated in the highly selective synthesis of the side chain of scyphostatin in 28% yield over nine steps in the longest linear sequence from allyl alcohol. Thus, this new tandem protocol has been emerged as the most widely applicable and highly selective route to trisubstituted alkenes including those that are otherwise difficult to prepare.