Mukaiyama s reagent

Mukaiyama s Reagent (2-Chloro-l-methyl pyridinium Iodide or 2-Fluoro-l-methyl pyridinium p-toulenesulfonate)... 

A closely related method, which often gives higher yields, involves treatment of the hydroxy acids with 1-methyl- or l-phenyl-2-halopyridinium salts, especially l-methyl-2-chloropyri-dinium iodide (Mukaiyama s reagent).6 3 Another method uses organotin oxides.644... 

Scheme 37 Diastereoselective preparation of spiro-P-lactams using 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). 

The cyclic ketenes were generated from /V-acy 1-1,3-thiazolidine-2-carboxylic acids by means of Mukaiyama s reagent. The same reaction generated enantio-merically pure 1,3-thiazolidine-derived spiro-p-lactams, using optically active /V-A rt-butoxycarbonyl-1,3-thiazolidine-2-carboxylic acid derivatives as precursors of the asymmetrical chiral cyclic ketenes (7< r/-butoxy carbonyl Boc) [101]. 

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... 

Coupling of 69 with methyl 4-hydroxyphenoxyacetate 70 was carried out in the presence of imidazole and confirmed by gel-phase 13C NMR of PSDES resin 71. The hydrolysis of resin-bound ester was efficiently achieved using trimethyltin hydroxide (TMTOH) [110-114] to give the corresponding immobilized carboxylic acid 72. For the key Staudinger reaction, activation of the carboxylic acid 72 by Mukaiyama s reagent 74 was employed (Scheme 20) [115-117]. The m-p-lactam 16 was obtained in a 12-14% isolated yield. 

RCHiCOOH - RCH=C—0.i Mukaiyama s reagent has been used for macro-lactonization of -hydroxy carboxylic acids (14,117-118). However, reaction of the substrate 2 with 1 and N(C2H5)3 in refluxing CH3CN does not lead to the expected... 

Immunosuppressant (-)-FK-S06 (2). This 23-membered lactone-lactam resembles cyclosporin A, a macrocyclic polypeptide, in that they both inhibit immune responses to transplantation, but FK-506 seems to be more active. The total synthesis of (- )-FK-506 has been achieved by a process research group at Merck.1 The cyclization to a carboxamide was carried out with Mukaiyama s reagent (1) under high dilution in 81% yield. The most unusual feature of 2 is the presence of a three-keto sequence at C8, C9, and C,(l (hemiketal). 

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. °... 

Preparative Methods the ligand can be obtained through reaction of 2 equiv of 2-pyridinecarboxylic acid with (1R,2R)-1,2-diaminocyclohexane using Mukaiyama s reagent or via the acid chloride. ... 

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... 

Yong, Y. F Kowalski, J. A. Lipton, M. A. Facile and Efficient Guanylation of Amines Using Thioureas and Mukaiyama s Reagent, J. Org. Chem. 1997,... 

---