Chemistry of Unsymmetrical C1-Substituted Oxabenzonorbornadienes

Abstract

: Oxabenzonorbornadiene (OBD) is a useful synthetic intermediate which can be readily activated by transition metal complexes with great face selectivity due to its dual-faced nature and intrinsic angle strain on the alkene. To date, the understanding of transition-metal catalyzed reactions of OBD itself has burgeoned; however, this has not been the case for unsymmetrical OBDs. Throughout the development of these reactions, the nature of C1-substituent has proven to have a profound effect on both the reactivity and selectivity of the outcome of the reaction. Upon substitution, different modes of reactivity arise, contributing to the possibility of multiple stereo-, regio-, and in extreme cases, constitutional isomers which can provide unique means of constructing a variety of synthetically useful cyclic frameworks. To maximize selectivity, an understanding of bridgehead substituent effects is crucial. To that end, this review outlines hitherto reported examples of bridgehead substituent effects on the chemistry of unsymmetrical C1-substituted OBDs.

Transition-metal-catalyzed domino reactions of strained bicyclic alkenes

“…Bicyclic alkenes, a family of strained ring systems, have seen widespread applications in organic synthesis in the last 20 years [ 2 – 6 ]. Broadly speaking, bicyclic alkenes can be classified into two groups: homobicyclic and heterobicyclic alkenes.…”

Iridium-catalyzed hydroacylation reactions of C1-substituted oxabenzonorbornadienes with salicylaldehyde: an experimental and computational study

“…Although OBD 1 has been shown to undergo many different modes of reactivity in both a stereo- and enantioselective manner, the regioselectivity of such reactions is still undefined ( Scheme 1 ) [ 58 ]. While the chemistry of symmetric OBD derivatives is well established, their unsymmetrically substituted counterparts 5 have remained underexplored ( Scheme 1 ).…”

“…In their seminal report, the authors were able to produce hydroacylated adducts 15a and 15b in good yield. On the basis of the aforementioned literature, several different products can be formed based on a complex relationship between the reactants, C 1 -substituent, and reaction conditions [ 58 ]; therefore, it is paramount to understand of the effects that C 1 -substitution has on the reactions. Inspired by the initial work of Nishimura and co-workers [ 64 ], we pursued a study on the effects of C 1 -substitution on the iridium-catalyzed hydroacylation reactions of unsymmetrical OBDs with salicylaldehyde.…”

“…In their seminal report, the authors were able to produce hydroacylated adducts 15a and 15b in good yield. On the basis of the aforementioned literature, several different products can be formed based on a complex relationship between the reactants, C 1 -substituent, and reaction conditions [58]; therefore, it is paramount to understand of the effects that C 1 -substitution has on the reactions.…”

Progress Towards the Total Synthesis of Nogalamycin using a Benzyne Cycloaddition Strategy

“…Despite the wealth of literature on the ring-opening of OBDs, there are few reported methods capable of accessing the substitution required for NOG. Most reported OBD ringopenings introduce substitution on the cyclohexane ring located β to the newly generated alcohol; [35][36][37] anthracyclines typically do not have substitution at this position. Thus, we opted to first synthesize a model OBD 18 (Scheme 3) to evaluate the likelihood of success in the application of known literature conditions to the advanced OBD scaffold that is needed for NOG.…”