Mukaiyama reagent

Scheme 15 Parallel synthesis of 2-oxazolines from carboxylic acids and aminoalcohols using PS-Mukaiyama reagent...

The effect of micelles in the pre-organization of acyclic compounds in a thir-teen-membered lactam formation using a modified Mukaiyama reagent was investigated by Rico [9]. 

Scheme7.112 Polymer-supported Mukaiyama reagent for amide synthesis.

Mukaiyama reagent such as 2-chloro-l-methyl-pyridinium iodide for esterification or amide formation. 

Amide formation using the Mukaiyama reagent follows a similar mechanistic pathway." ... 

A short asymmetric synthesis of the 2-ketocarbacepham (27) involving as the initial step for the preparation of the starting piperidone, a hetero Diels-Alder reaction of the benzylimine derived from the enantiomer of Gamer s aldehyde with Danishesky s diene, has been described <02JOC598>. The key cyclization step to form the bicyclic P-lactam system was achieved from a P-amino acid precursor using the Mukaiyama reagent, 2-chloro-A-methylpyridinium iodide. 

The Mukaiyama reagent, l-methyl-2-chloropyridinium iodide (28), is also suitable for macrolactamization [85]. Jones et al. [86] achieved the first total synthesis of the important immunosupressant (-)-FK-506 (151) using the Mukaiyama method as a key cyclization step. As shown in Scheme 50, the unstable amino acid 149 was treated with 28 under high dilution to give the macrocycle 150 in... 

Figure 1 Rates of Guanidinylation of Benzylamine with iV -Bis(tert-butoxycarbonyl)-S-methylisothiourea ( ), iV,iV -Bis(te/r-butoxycarbonyl)pyrazole-l-carboximidamide ( ), Ai,Ai -Bis(tert-butoxycarbonyl)thiourea in the Presence of the Mukaiyama Reagent ( ), and l,3-Bis(tert-butoxycarbonyl)-2-triflylguanidine ( )...

Efficient asymmetric induction was achieved in [2 + 2] cycloadditions when carbohydrate-derived oxazolidinones were used [31]. Treatment of the acid 36 with the Mukaiyama reagent (2-chloro-l-methylpyridinium iodide) generated the ketene, which was added to imines 37, giving the c/ --P-lactams 38 with excellent diastereomeric excess (Scheme 10.9, Table 10.2). 

N-Methoxy-N-methylamides. A convenient preparation of RCON(OMe)Me from carboxylic acids employs the Mukaiyama reagent. 

To a solution of the acid (300 mg, 1.1 mmol) in CH2CI2 (5 mL) was added 2-chloro-1-methyl-pyridinium iodide (the Mukaiyama reagent, 330 mg, 1.3 mmol) and the aniline (1.29 g, 5.89 mmol). The mixture was heated at reflux for 1 h and then allowed to cool. EtsN (0.30 mL, 2.2 mmol) was added, and the mixture was heated at reflux for an additional 20 h, allowed to cool, poured into water (40 mL), and extracted with CH2CI2 (3 x 20 mL). The combined organic extracts were dried, filtered, and concentrated. The crude material was purified by column chromatography (25% EtOAc in hexanes) to furnish the amide (387 mg, 75%). 

Polymer supported pyridinium salts, such as Mukaiyama reagent, have proven very useful synthetic tools in the preparation of 2-oxazoline libraries 05JC0688> and in automatable esterification reactions <05TL2817>. Yamamoto et al. have examined the use of polymer supported boronopyridinium salts for the preparation of amides and esters in good to excellent yield <050L5043,05TL5047>. 

Scheme 7.16 Preparation of polystyrene resin-supported Mukaiyama reagent 49.

Scheme 7.17 Preparation of Wang resin-supported Mukaiyama reagent 51.

A differently anchored Mukaiyama reagent is the N-methylpyridinium iodide salt 57 [71], which has been obtained by reaction of the Merrifield resin with N-Boc-aminocaproic acid in the presence of cesium carbonate to give the supported ester 55 (Scheme 7.19). Further Boc-deprotection and reaction with 6-chloronicoti-noyl chloride in the presence of Hxinig s base furnished the anchored 2-chloro-pyridine 56, which was transformed into the final N-methylpyridinium salt 57 after N-methylation in neat methyl iodide. This supported reagent has been used in the rapid microwave-assisted esterification of carboxylic acids and alcohols in the presence of triethylamine as base, with dichloromethane as solvent at 80 °C, the products being obtained in high purity after simple resin filtration [72],... 

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