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. 2011 Nov;353(16):2981-2987.
doi: 10.1002/adsc.201100420.

Highly(≥98%) Stereo- and Regioselective Trisubstituted Alkene Synthesis of Wide Applicability via 1-Halo-1-alkyne Hydroboration-Tandem Negishi-Suzuki Coupling or Organoborate Migratory Insertion Protocol

Shiqing Xu  1 , Ching-Tien Lee, Honghua Rao, Ei-Ichi Negishi
Affiliations

Highly(≥98%) Stereo- and Regioselective Trisubstituted Alkene Synthesis of Wide Applicability via 1-Halo-1-alkyne Hydroboration-Tandem Negishi-Suzuki Coupling or Organoborate Migratory Insertion Protocol

Shiqing Xu et al. Adv Synth Catal. 2011 Nov.

Abstract

(Z)-1-Halo-1-alkenylboranes (7), preparable in 82-90% 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 of 7 with organolithium or Grignard reagents to generate α-bromo-1-alkenylboronate complexes (10) that can undergo migratory insertion of a carbon group (R2) to form (E)-alkenylboranes (11) with inversion of alkene configuration (≥98% inversion), followed by fluoride-promoted Suzuki alkenylation, and (iii) Negishi coupling to generate (Z)-alkenylboranes (8) 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 side chain (4) 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.

Keywords: (Z)-1-halo-1-alkenylborane; Palladium-catalyzed cross-coupling; alkene synthesis; alkenylation; hydroboration.

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Figures

Scheme 1
Scheme 1
Carbonyl olefination and alkyne elementometalation–Pd-catalyzed alkenylation
Scheme 2
Scheme 2
H-to-T construction route to stereodefined trisubstituted alkenes.
Scheme 3
Scheme 3
Syntheses of the C7-C16 fragment 4 of the side-chain of scyphostatin.
Scheme 4
Scheme 4
T-to-H construction route to stereodefined trisubstituted alkenes.
Scheme 5
Scheme 5
An enantioselective T-to-H route to the C7-C16 fragment 4 of the side-chain of (+)-scyphostatin
See this image and copyright information in PMC

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