The Mukaiyama Reagent: An Efficient Condensation Agent

Introduction

The Mukaiyama reagent (2-chloro-1-methylpyridinium iodide, CMPI) is one of the most valuable reagents for ­activation of hydroxyl groups of carboxylic acids and ­alcohols.[ ¹ ] It is a pale yellow crystalline solid which is stable at room temperature in closed containers under normal storage and handling conditions. CMPI is commercially available, but can be easily synthesized from 2-chloro­pyridine and methyliodide.[2a] [b] [c] [d]

Scheme 1

It is widely used for the synthesis of esters,[ ³ ] lactones,[ ⁴ ] ­amides,[ ⁵ ] lactams,[ ⁶ ] and ketenes[ ⁷ ] from the corresponding carboxylic acids, as well for obtaining carbodiimides from thioureas[ ⁸ ] and thiocyanates from alcohols.[ ⁹ ] CMPI was introduced as an useful reagent for the synthesis of carboxylic esters by Teruaki Mukaiyama in 1975,[ ¹⁰ ] after that the miscellaneous N-alkyl-2-halopyridinium salts had been developed as activating agents.[ ¹ ] Nowadays, several polymer-supported CMPI analogues have been used for the synthesis of esters and amides due to user-friendly purification procedures.[ ¹¹ ] The reagent analogues are also valuable for peptide synthesis.[ ¹² ]

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