Fukuyama-Mitsunobu procedure

Transformation of a primary amine to a secondary amine using 2,4-dinitro-benzenesulfonyl chloride and an alcohol. Also known as Fukuyama-Mitsunobu procedure. 

This reaction was initially reported by Fukuyama and co-workers in 1995. It is a two-step conversion of primary amines into secondary amines via ortho-nitrobenzenesulfonation in conjunction with the Mitsunobu Reaction and subsequent removal of the o-nitrobenzenesulfonyl group by thiophenol. Therefore, this reaction is generally known as the Fukuyama amine synthesis. In addition, it is also referred to as the Fukuyama-Mitsunobu A -alkylation," Fukuyama-Mitsunobu alkylation, Fukuyama-Mitsunobu condition, Fukuyama-Mitsunobu procedure, or Fukuyama-Mitsunobu Reaction. In this reaction, the o-nitrobenzenesulfonyl-protected amine is alkylated with alcohol in the presence of PPhs and diethyl azodicarboxylate (DEAD) or diisopropyl azodicarboxylate (DIAD), and the deprotection occurs in a very mild condition (almost neutral ). The o-nitrobenzenesulfonyl group is simply called the Fukuyama sulfonamide protecting groupThis reaction has become a versatile method... 

Synthesis of Fmoc-(Me)Xaa1-OH by On-Resin Methylation Using the Fukuyama/Mitsunobu Reactions General Procedure 92 ... 

Although the reductive amination is very conunon in the synthesis of polyamines, it is not possible to generate protected C4- and Cs-aminoalde-hydes. This limits the procedure to the synthesis of philanthotoxins, in which the terminal alkyl spacer is not a C3 building block. For synthesis of the corresponding PhTX-433 (26), Bychroft and coworkers used the above described Fukuyama-Mitsunobu alkylation conditions [175]. 

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