Fukuyama indole synthesis
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The Fukuyama indole synthesis is a versatile tin mediated chemical reaction that results in the formation of 2,3-disubstituted indoles.[1] A practical one-pot reaction that can be useful for the creation of disubstituted indoles.[2] Most commonly tributyltin hydride is utilized as the reducing agent, with azobisisobutyronitrile (AIBN) as a radical initiator. Triethylborane can also be used as a radical initiator.[3] The reaction can begin with either an ortho-isocyanostyrene or a 2-alkenylthioanilide derivative, both forming the indole through Radical cyclization via an α-stannoimidoyl radical.[4] The R group can be a range of both basic and acidic sensitive functional groups such as esters, THP ethers, and β-lactams. In addition the reaction is not stereospecific, in that both the cis and trans isoform can be used to obtain the desired product.[5]
The reaction mechanism begins with the creation of the tributyl tin radical with either AIBN or triethylborane, not shown in either step-wise mechanism. Following the radical attacks the o-isocyano carbon creating the alpha-stannoimidoyl radical. Through radical cyclization a five membered ring is formed followed by the propagation of a new tin radical. The final step is dependent on the desired outcome of the reaction. This reaction is a one-pot synthesis and results in yields ranging from 50% to 98% depending on the substituent.[1]
The mechanism using 2-alkenylthioanilide is very similar, also starting with the formation of a bond, now between the tin radical and the sulfur. Followed by a similar radical cyclization resulting in a five membered ring, a new tin radical is produced and the original attacking radical leaves with the sulfur substituent. This part of the step-wise mechanism has yet to be detailed. The reaction yield can range from 40% to 93% depending also on the desired substituent.
