α‐Arylation and Ring Expansion of Annulated Cyclobutanones: Stereoselective Synthesis of Functionalized Tetralones

Abstract

a-Arylcyclobutanones displayunique reactivity that makes them valuable synthetic intermediates and target molecules.W ed escribe the preparation of a-aryl-and aheteroarylcyclobutanones through ad irect a-arylation reaction. Problematic fragmentations are avoided by the use of LiO t Bu, whichp romotes ar apid but reversible self-aldol reaction that slowly releases the enolate required for aarylation. We also demonstrate the ring expansion of aarylcyclobutanones,aprocess that is highlighted in the stereoselective synthesis of 1-methoxyc oniothyrinone D.

(−)‐Isoscopariusin A, a Naturally Occurring Immunosuppressive Meroditerpenoid: Structure Elucidation and Scalable Chemical Synthesis

“…Attempts to proceed the Ni-catalyzed arylation of the achloroketone 20 met with failure. [21] Under the conditions reported by Britton and co-workers for the arylation of cyclobutanones [(D t BPF)PdCl 2 ,L iO t Bu, 4-bromoanisole, THF,6 0 8 8C], [22] a-arylcyclobutanone 21 was obtained from cyclobutanone 13 in 23 %y ield due to the poor diastereoselectivity. In the first route for the synthesis of the tricyclic core of 1, 19 from 7 (Scheme 3), intermolecular [2+ +2] thermal cycloaddition between dichloroketene and trisubstituted alkene was applied to assemble dichlorocyclobutanones.A lthough Shapiro coupling reaction followed by 1,4-addition furnished the key intermediate with af unctionalized cyclobutane core bearing two chiral centers,t he mismatched C8' stereochemistry and the subsequent operation of configuration inversion significantly lowered the overall efficiency.T herefore,w e explored an alternative strategy in which a-arylcyclobutanones were first established, followed by face-selective homologation to access the key cyclobutane skeleton with four chiral centers.W ith these thoughts in mind, we undertook aretrosynthetic analysis of 1 (Figure 6).…”