Polymer-supported Mukaiyama reagent

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

The first use of a polymer-supported Mukaiyama reagent for microwave-mediated synthesis of amides was presented in 2004 [125]. To prove its effectiveness, even in difficult coupling reactions, it was used in the microwave-accelerated synthesis of an amide from sterically hindered pivalic acid (Scheme 16.83). The mixture was subjected to microwave irradiation at 100 °C for 10 min and the desired product was obtained in 80% yield. 

Scheme 16.84. Solution-phase esterification by use of a polymer-supported Mukaiyama reagent.

The majority of reported solid-phase combinatorial syntheses of the lactam core utilize a [2-i-2] cycloaddition reaction of ketenes with resin-bound imines [33-41]. A further development of the Staudinger reaction was reported by Mata and coworkers using Mukaiyama s reagent [42]. In addition, a stereoselective synthesis of chi-rally pure P-lactams has been performed as a first utilization of polymer-supported oxazolidine aldehydes [43]. Other strategies include an ester enolate-imine condensation [44], an Hg(OCOCF3)2-mediated intramolecular cydization [45], and Miller hydroxamate synthesis [46]. Because of the variability derived from the scaffold synthesis, not many attempts have been made to derivatize the resin-bound lactam template [47]. One of the most detailed descriptions of a versatile (3-lactam synthesis on a resin employed amino acids tethered as esters on Sasrin resin [48]. 

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>. 

Reagent 13 was also used under microwave conditions to create a library of esters.7 Another polymer supported version of Mukaiyama s reagent (16) was disclosed by Swinnen.8... 

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