Direct, chemoselective N-tert-prenylation of indoles by C-H functionalization.
Direct, chemoselective N-tert-prenylation of indoles by C-H functionalization.
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DOI：
10.1002/anie.200902761
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发表时间：
2009
影响因子：
16.6
通讯作者：
Baran, Phil S.
中科院分区：
文献类型：
--
作者：
Luzung, Michael R.;Lewis, Chad A.;Baran, Phil S.
Prenylated indole alkaloids have long been targets for total synthesis, since they possess a broad range of medicinal properties and intriguing architectures.[1] Our interest in this family began with the stephacidin family of indole alkaloids,[2] during which the fortuitous finding shown in Scheme 1a was made. Thus, in 2003, during an attempt to convert N-Boctryptophan methyl ester (1) into the C-2 prenylated tryptophan 2 directly using 2-methyl-2-butene by electrophilic palladation [3] and olefin capture, we instead observed small amounts (< 10%) of a nonpolar compound which was identified as N-tert-prenylated indole 3. Whereas many elegant methods have been invented for accomplishing the direct prenylation of indoles,[4–7] no methods currently exist for the direct N-tert-prenylation of indoles (Scheme 1b).[8] Inspired by our initial findings, we herein delineate a mild, highly chemoselective, scalable, and one-step route to these biologically relevant motifs by CÀH functionalization. The only known route to N-tert-prenylated indoles requires a four-step sequence, three of which involve nonstrategic redox fluctuations [9](Scheme 1 c): 1) reduction of the indole to the indoline, 2) propargyl substitution by CuI catalysis, 3) oxidation back to the indole, and finally 4) Lindlar reduction of the alkyne to the olefin. This chemistry has been successfully incorporated into a number of total syntheses.[9]Building on our initial observations (Scheme1a), we envisioned a direct, one-step procedure to synthesize N-tertprenylated indoles without the use of prefunctionalized starting materials and superfluous redox steps—well-known tenets of CÀH functionalization logic.[10] Such a strategy would be orthogonal to routes that involve nucleophilic prenylation, which in this case would not be applicable.[11] Specifically, CÀH activation of indoles is known to occur at C-2 or C-3, and involves the direct coupling of arenes [12] and electron-deficient olefins [13] and annulations,[2, 9, 14] even in the presence of free NÀH indoles.[15] Palladium-catalyzed intra-
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影响因子：
15
作者：
Lane, BS;Brown, MA;Sames, D
通讯作者：
Sames, D
影响因子：
15
作者：
Brice, JL;Harang, JE;Stahl, SS
通讯作者：
Stahl, SS
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3.6
作者：
Hartwig, JF;Kawatsura, M;Alcazar-Roman, LM
通讯作者：
Alcazar-Roman, LM
影响因子：
5.2
作者：
Chang, HM;Cheng, CH
通讯作者：
Cheng, CH
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作者：
Fletcher, Anthony J.;Bax, Matthew N.;Willis, Michael C.
通讯作者：
Willis, Michael C.