Nitrile Oxides Mukaiyama procedure

Generation of nitrile oxides by the Mukaiyama procedure, viz., dehydration of primary nitroalkanes with an aryl isocyanate, usually in the presence of Et3N as a base, is of high importance in nitrile oxide chemistry. Besides comprehensive monographs (4, 5), some data concerning the procedure and its use in organic synthesis can be found in References 61 and 62. 

Highly efficient modifications of Mukaiyama s procedure, convenient for combinatorial syntheses, were reported recently, namely the polymer-supported synthesis of isoxazolines via nitrile oxides, starting from primary nitroalkanes, in a one-pot process (75) and by microwave activation of the process (73). 

Kozikowski s group has been particularly active in the application of the INOC reaction toward the construction of a variety of natural products. One of the many examples from his laboratory involves the synthesis of tetracyclic compounds possessing suitably functionalized C rings for elaboration to a diverse number of ergot alkaloids via the INOC reaction. A total synthesis of chanoclavine I (65) was accomplished by this chemistry (Scheme 15). The key step in the synthesis involved the conversion of the nitro group of indole (62) into the corresponding nitrile oxide using the phenyl isocyanate procedure developed by Mukaiyama.57 The major product corresponded to isoxazoline (64). The isoxazoline nucleus was converted into chanoclavine I (65) in a series of subsequent steps. The application of nitrile oxide cycloaddition chemistry to the construction of other natural products can be expected to be an active area in future years. 

Zagozda and Plenkiewicz reported a synthesis of enantiopure isoxazolines 103 via 13DC of optically active nitrile oxides 101 with MVK and acrylate 102 (Scheme 28) [ 122], The nitrile oxide precursor 100 was prepared from ni-troalkenes 99a,b by Baker s yeast promoted reduction. While the Mukaiyama procedure (PhNCO, EtsN) was satisfactory for the generation of nitrile oxide 101 in some cases, the Hassner method (B0C2O, DMAP) provided better results in other cases. Although yields were satisfactory (35-55%), stereoselectivity remained low (<65 35). 

Chapter Synthesis of 12- to 16-Membered-Ring Lactones is dedicated to the synthesis of 12- to 16-membered ring lactones. In this chapter, M. Kalesse and M. Cordes present an overview of the macrocyclization of seco-acids as well as new effective procedures to access 12- to 16-membered ring lactones such as ringclosing metatheses of alkynes and olefins. The authors also report the use of ketene sources and benzodioxinones to produce macrocyclic lactones. Nitrile oxide-olefin cycloaddition, intramolecular C-H oxidative macrolactonization, and Yamaguchi and Mukaiyama macrocyclization as well as macrolactonization via thioester or using phosphorus reagents are described. 

---