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Review
. 2010 Apr 12;49(17):2978-86.
doi: 10.1002/anie.200905657.

Silicon-based cross-coupling reactions in the total synthesis of natural products

Scott E Denmark  1 , Jack H-C Liu
Affiliations
Review

Silicon-based cross-coupling reactions in the total synthesis of natural products

Scott E Denmark et al. Angew Chem Int Ed Engl. .

Abstract

Unlike other variants of transition-metal-catalyzed cross-coupling reactions, those based on organosilicon donors have not been used extensively in natural product synthesis. However, recent advances such as: 1) the development of mild reaction conditions, 2) the expansion of substrate scope, 3) the development of methods to stereoselectively and efficiently introduce the silicon-containing moiety, 4) the development of a large number of sequential processes, and 5) the advent of bifunctional bis(silyl) linchpin reagents, signify the coming of age of silicon-based cross-coupling reactions. The following case studies illustrate how silicon-based cross-coupling reactions play a strategic role in constructing carbon-carbon bonds in selected target molecules.

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Figures

Scheme 1.
Scheme 1.
Key steps in the synthesis of NK-104.[,]
Scheme 2.
Scheme 2.
The Heck reaction/cross-coupling sequence in the formal synthesis of nitidine.[24]
Scheme 3.
Scheme 3.
Medium-sized ring formation using sequential RCM/intramolecular cross-coupling reaction.[28]
Scheme 4.
Scheme 4.
The key ring-closure steps in the total synthesis of brasilenyne.[27] PMB=para-methoxybenzyl.
Scheme 5.
Scheme 5.
Key carbon–carbon bond-forming reactions in the total synthesis of herboxidiene/GEX 1A.[32] Bn=benzyl, DTBP=2,6-di-tert-butyl-pyridine, TBDPS=tert-butyldiphenylsilyl, Tf=trifluoromethanesulfonyl, TMS=trimethylsilyl.
Scheme 6.
Scheme 6.
Sequential cross-coupling of 1,4-bis(silyl)diene 22.[10d] dba=trans,trans-dibenzylideneacetone.
Scheme 7.
Scheme 7.
Preparation of the unsymmetrical polyene fragment of RK-397 using 22.[34] THP=tetrahydropyran.
Scheme 8.
Scheme 8.
The preparation and the cross-coupling of dihydropyranylsilanol 28.[7d]
Scheme 9.
Scheme 9.
The assembly of the C-aryl glycoside of papulacandin D.[36] Piv=pivaloyl, TES=triethylsilyl.
Scheme 10.
Scheme 10.
Key steps leading to the synthesis of isodomoic acid H.[37] Ts=4-toluenesulfonyl.
Scheme 11.
Scheme 11.
Conclusion of the synthesis of isodomoic acid G.[37] TIPS=triisopropylsilyl.
See this image and copyright information in PMC

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