One‐Pot Cannizzaro Cascade Synthesis of ortho‐Fused Cycloocta‐2,5‐dien‐1‐ones from 2‐Bromo(hetero)aryl Aldehydes

Abstract

An intramolecular Cannizzaro-type hydride transfer to an in situ prepared allene enables the synthesis of orthofused 4-substituted cycloocta-2,5-dien-1-ones with unprecedented technical ease for an eight-ring carboannulation. Various derivatives could be obtained from commercially available (hetero)aryl aldehydes,t rimethylsilylacetylene,a nd simple propargyl chlorides in good yields.Readily(oftencommercially)available2-bromo(hetero)aryl aldehydes (1,S cheme 1) constitute powerful and popular units for the construction of ortho-fused carbocyclic rings. [1] Tw os trategies commonly employed in the multitudinous syntheses described in the literature involve 1) the derivatization of 1 to intermediates of type A,w ith a p-system attacking an electrophile that is ultimately derived from the aldehyde by functional-group manipulations (e.g., an alcohol, acetal, or even the aldehyde itself);o r2 )formyl group homologation to an anion-stabilizing unit that attacks as uitably activated p-bond (B). Whereas many elegant catalytic systems that use intermediates A or B have already been described, [2,3] thep reparation of the suitable precursors is often step-intensive,r aising questions on the overall process efficiency in the "age of sustainability".[4] We speculated that an ew annulation strategy,b ased on aC annizzaro-type reaction via intermediate C,might be possible.Asthe hydride transfer simultaneously exposes apowerful Michael acceptor (ynone or equivalent) and ac arbanion in close proximity, efficient annulation might be expected to occur (especially if C is directly attained in situ). Herein, we describe the use of such as trategy for the formation of eight-membered rings. Thep aucity of direct single-pot/step procedures to such medium rings attests to the known issues associated with their synthesis;[5] they therefore provide as tringent test for strategy C. Although redox-based Cannizzaro reactions, including asymmetric and triggered C À Cb ond-forming versions,h ave recently been developed, [6] to the best of our knowledge,they have not been employed for carboannulation reactions to medium rings.G enuine single-pot/step procedures to eight-membered rings are very limited-Reppes historical catalytic access to cyclooctatetraene [7] and Murakamis [4+ +2+ +2] approach [8] being notable exceptions.Modern alternatives frequently describe catalytic cyclizationst hat proceed with exquisitely high yields (for the final step). Unfortunately,t heir overall synthetic efficiency is often compromised by the multistep syntheses required to obtain the cyclization precursors.[9]