Abstract
The asymmetric synthesis of N-allylic indoles is important for natural product synthesis and pharmaceutical research. The regio- and enantioselective N-allylation of indoles is a true challenge due to the favourable C3-allylation. We develop here a new strategy to the asymmetric synthesis of N-allylic indoles via rhodium-catalysed N-selective coupling of aryl hydrazines with allenes followed by Fischer indolization. The exclusive N-selectivities and good to excellent enantioselectivities are achieved applying a rhodium(I)/DTBM-Segphos or rhodium(I)/DTBM-Binap catalyst. This method permits the practical synthesis of valuable chiral N-allylated indoles, and avoids the N- or C-selectivity issue.
Highlights
The asymmetric synthesis of N-allylic indoles is important for natural product synthesis and pharmaceutical research
We report a rhodium-catalysed regio- and enantioselective coupling of aryl hydrazines with terminal allenes, which lead to the asymmetric synthesis of N-allylic indoles by following a Fischer indolization (Fig. 1c)
Control experiments indicated that both rhodium catalyst and ligand are necessary for the coupling reaction of aryl hydrazine with allene to proceed (Table 1, entries 10 and 11)
Summary
The asymmetric synthesis of N-allylic indoles is important for natural product synthesis and pharmaceutical research. We envisioned that a transition metal-catalysed asymmetric N1-selective coupling of aryl hydrazines with terminal allenes[34,35,36,37,38,39,40] could lead to the synthesis of chiral N1-allylic aryl hydrazines. We report a rhodium-catalysed regio- and enantioselective coupling of aryl hydrazines with terminal allenes, which lead to the asymmetric synthesis of N-allylic indoles by following a Fischer indolization (Fig. 1c).
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