Tandem Inter [4 + 2]/Intra [3 + 2] Cycloadditions of Nitroalkenes. 15. The Bridged Mode (α-Tether)

Abstract

A new variant of the tandem inter [4 + 2]/intra [3 + 2] cycloaddition of nitroalkenes is described in detail. The scope and limitations of the bridged mode tandem cycloaddition in which the diene and dienophile are part of the same molecule are documented. Simple 1,4-pentadienes as well as 2-alkoxy-1,4-pentadienes can function effectively as dienophile and dipolarophile combinations with excellent chemical selectivity and regio- and diastereoselectivities. Hydrogenation of the bridged nitroso acetals produces aminocyclohexanemethanol derivatives in high diastereo- and enantioselectivities. Further, insights into the mechanistic aspects of the Raney nickel promoted hydrogenation are reported. An intriguing influence of the nitro olefin α-substituent on the diastereoselectivity in the [4 + 2] cycloaddition has been documented. The reactivity of the α-chloro-substituted nitroalkene 26 as the heterodiene in the Diels−Alder reaction is assayed, and the use of the chlorine atom as a hydrogen surrogate is described.

Diastereoselective synthesis of nitroso acetals from (S,E)-γ-aminated nitroalkenes via multicomponent [4 + 2]/[3 + 2] cycloadditions promoted by LiCl or LiClO4

“…In the [3 + 2] cycloadditions, we believe that in the TS the respective nitronates present a half-chair conformation with the HC(4) substituent and the alkoxy group in an axial position to maximize the stabilization generated by the anomeric effect [9,33,41–42]. Thus, the competitive endo / exo approach of the 1,3-dipolarophile occurred by the Re face on the opposite side to the bulky lateral chain at HC(4).…”

Nitroalkenes as Amination Tools

“…The inclusion of a further unsaturation in the dienophile, as is the case in 2 -alkoxy -1,4 -dienes, allows tandem [4+2]/[3+2] cycloadditions in which bridged nitroso acetals 108 are formed after the intermediate cyclic nitronates have been heated at refl ux for prolonged periods (Scheme 3.59 ) [116,117] . Compounds 108 are the products of α -tethered processes and upon reduction give amino cyclohexanols 109 closely reminiscent of aminocarbasugar compounds.…”

Six-membered cyclic nitronates in the stereoselective synthesis of natural and bioactive compounds

“…The classic use of cyclic nitronates 1 in directed synthesis, developed by Prof. Denmark, consists in their use as 1,3-dipoles in cycloaddition with functionalized olefins [3]. This process can be carried out both as intermolecular or intramolecular [3,[6][7][8][9]. In all cases the resulting bi-or polycyclic nitrosoacetals 2 are formed with high stereoselectivity, which allows them to be used as close precursors of diasteromerically and enantiomerically pure natural products and their analogs [3,[6][7][8][9][10][11][12][13].…”

“…This process can be carried out both as intermolecular or intramolecular [3,[6][7][8][9]. In all cases the resulting bi-or polycyclic nitrosoacetals 2 are formed with high stereoselectivity, which allows them to be used as close precursors of diasteromerically and enantiomerically pure natural products and their analogs [3,[6][7][8][9][10][11][12][13]. Thus, reduction of the N-O bonds in these nitrosoacetals, depending on their structures, leads to various polycyclic saturated systems containing a _______ *To whom correspondence should be addressed, e-mail: iof@ioc.ac.ru yrrolizidinone skeleton.…”