Synthesis of Acylnitroso Intermediates and Their Synthetic Applications

Abstract

Acylnitroso intermediates are usually known as super reactive species, always prepared in situ and can be readily trapped via hetero-Diels-Alder reactions with dienes or with olefins via ene reactions, which open a magnificent access to produce a variety of complicated and very demanding organic molecules. Both of these reactions of acylnitroso species have been proved as the key synthetic tool in the total synthesis of natural products. The synthetic methods used to prepare these intermediates as well as their recent synthetic applications to the total synthesis of natural products are briefly described in this minireview.

Solid-Supported Nitroso Hetero Diels–Alder Reactions. 1. Acylnitroso Dienophiles: Scope and Limitations

“…44 In general, the major regioisomer of each set contained the bulkier group attached to the C6 carbon of the dihydro [1,2] oxazine ring.…”

“…The appeal of acyl-and arylnitroso hetero-Diels-Alder (HDA) reactions [1][2][3][4][5] for the creation of novel structural and functional diversity in chemical space consists of the formation of two new carbon-heteroatom bonds, while simultaneously introducing a rigid element, the dihydro [1,2]oxazine ring, that dramatically changes the original spatial arrangement of the incoming diene. These attributes, coupled with the immense diversity of accessible dienes, particularly those that originate from natural products, 6 make HDA reactions attractive for the generation of new molecular libraries.…”

“…From the chemical point of view, the immobilization of nitroso dienophiles represents the more challenging task because the more-reactive species is immobilized on the solid support. Although both acyland arylnitroso HDA reactions yield dihydro [1,2]oxazine derivatives, the syntheses, properties, and reactivity of acyland arylnitroso dienophiles differ substantially and therefore they will be dealt with independently in two consecutive contributions. 44…”

Intramolecular carbonyl nitroso ene reaction: recent developments

“…However, the reaction works well only with terminal alkenes 1 (R = H) but for internal alkenes the yields are poor [5]. In Rh(I) catalyzed C-H insertion of nitrenes, excellent results have been achieved for benzylic amination, whereas in the case of related homoallylic systems, such as 1, C-H insertion competes with aziridination, furnishing mixtures of compounds 2 and 3 (Scheme 1) [6][7][8].Scheme 1The nitroso ene reaction represents a type of allylic amination that does not rely on the use of noble metal catalysts [9][10][11]. An intramolecular variant of the carbonyl nitroso ene reaction to form saturated heterocycles 7 (Scheme 2) was reported by Kirby [12-16] more than two decades ago, but since then it has remained unexplored.…”

“…The nitroso ene reaction represents a type of allylic amination that does not rely on the use of noble metal catalysts [9][10][11]. An intramolecular variant of the carbonyl nitroso ene reaction to form saturated heterocycles 7 (Scheme 2) was reported by Kirby [12][13][14][15][16] more than two decades ago, but since then it has remained unexplored.…”