2-Chloro-l-methylpyridinium iodide Mukaiyama’s reagent

Treatment of amino acid 156, imine and 2-chloro-l-methylpyridinium iodide (Mukaiyama s reagent) in the presence of triethylamine in refluxing dichloro-methane afforded spiro-(3-lactams 157,158. These were obtained as a 1.8 1 mixture of diastereoisomers and separated by column chromatography. The reaction of 159 and imine under the usual experimental conditions resulted in the formation of a single diastereoisomer 160. The absolute (3 S, 4 S, 7 -configuration was assigned on the basis of mechanistic considerations and XH NMR spectra. The presence of the stereocenter affords complete diastereoselectivity (only trans diastereoisomers 157, 158) and enantioselectivity (160). 

In continuation of the research on solid-phase synthesis of biologically interesting (3-lactam compounds towards the development of combinatorial libraries, Mata et al. [102] investigated use of 2-chloro-l-methylpyridinium iodide (Mukaiyama s reagent) as a key reagent for the construction of the (3-lactam ring in a stereoselective manner. The popular explanation involves the reaction of ketene B with the imine to form a zwitterionic intermediate D (Scheme 13). Alternatively, it is the activated acid A that acylates the imine to form the zwitterion D by abstraction of proton with... 

Enantiomerically pure 1,3-thiazolidine-derived spiro /3-lactams 505 and 506 were stereoselectively synthesized by means of a Staudinger ketene-imine reaction in the presence of 2-chloro-l-methylpyridinium iodide (Mukaiyama s reagent) starting from optically active A -BOC-l,3-thiazolidine-2-carboxylic acid derivatives 504 and imines (Scheme 127). The reactions were stereoselective and afforded spiro-/3-lactams with a /ra r -configuration. The spiro-/3-lactams 505 and 506 were transformed into enantiomerically pure chiral monocyclic /3-lactams 507 and 508... 

Also, polymer bound thioureas 29 are converted into carbodiimides 30 using Mukaiyama s reagent (2-chloro-l-methylpyridinium iodide) in the presence of triethy-lamine. This polymer is used in the solid phase synthesis of 2-aminoimidazolinones. °... 

The same group of workers has proceeded to develop an intramolecular version of the reaction. The aldehyde acids (35, n = 1 or 2) on treatment with Mukaiyama s reagent, 2-chloro-l-methylpyridinium iodide, and triethylamine afforded the cis substituted bicyclic lactones (36, n = 1 or 2). The authors have adduced evidence in support of a nucleophile-catalysed aldol lactonisation (NCAL) reaction mechanism rather than the alternative thermal [2+2] cycloaddition. They have also found that the intramolecular reaction, like the intermolecular process, is subject to asymmetric catalysis. When an optically active base such as 0-acetylquinidine was present in the reaction mixture, the bicyclic lactones were produced with high ee <01 JA7945>. 

Two new glucose-derived oxazolidinones have been prepared, and converted to iV-acyl derivatives of type 204 (R = Me or Piv). The dialkylboron enolates derived from 204 underwent aldol reactions to give syn-products 205, with diastereomeric ratios between 8 1 and 16 1. The same group has also made the oxazolidinone 206 from D-xylose. When this was treated with Mukaiyama s reagent (2-chloro-l-methylpyridinium iodide) in the presence of an imine, a Staudinger ketene-imine cyclization occurred to give a p-lactam such as 207, the structure of which was confirmed by X-ray crystallography, in >98% de. ... 

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