Palladium(ii) acetate mediated oxidative cyclization of ω-unsaturated α-cyano ketones. A facile methylenecyclopentane annulation process

Abstract

A highly efficient methylenecyclopentane annulation process has been developed based on the Pd(II)-mediated oxidative cyclization of omega-unsaturated alpha-cyano ketones, readily accessed via the Michael addition of 3-butenylmagnesium bromide with 2-cyano-2-cycloalkenones.

Total Synthesis of 1‐Hydroxytaxinine

“…= 7:1). [23,24] Thefollowing NaBH 4 reduction of the C4-ketone in one pot gave rise to the alcohol 16.The X-ray structure of 15 suggests that the bulky A-ring structure would block the bottom face of the C8-double bond and the desired C8 stereochemistry would be established by the favorable top face addition of the nucleophile.T he secondary alcohol of 16 was then sequentially treated with MsCl and Et 3 N, and with DBU, resulting in the formation of the a,b-unsaturated nitrile 17 by elimination of the mesylate.The nitrile 17 was reduced to the corresponding imine with diisobutylaluminum hydride,a nd the following acidic work-up simultaneously hydrolyzed the C2-imine and C1-acetal to produce the requisite ketoaldehyde 4.I ti si mportant to note that the C2-nitrile group has multiple roles in this route:i te nhances the reactivity of two 1,4-acceptors, 6 and 15,asanelectron-withdrawing group,and serves as aprecursor of the C2-aldehyde of 4.…”

Palladium‐Catalyzed Oxidative Carbocyclizations

“…Ketonitriles 12 bearing a pendant butene chain in the bposition were cyclized by means of a palladium-catalyzed oxidative cyclopentane annulation process (Scheme 7), [14] similar to that developed by Widenhoefer [12] and later used by Yang. [13] Facile enolization followed by an intramolecular carbopalladation generates intermediate M2, which upon bhydride elimination gives bicyclic oxonitrile 13.…”

Autoxidative Annulation Cascade of the α-Cyano β-TMS-capped Alkynyl Cycloalkanone System

“…In continuation of our studies on α-activated cross-conjugated cycloalkenone systems in organic synthesis, − 2-cyano-2-cyclohexenone ( 1 ) was found to be a highly reactive Michael acceptor to facilitate 1,4-conjugate addition with 1-(trimethylsilyl)-1-butyn-4-yl magnesium chloride to give the corresponding ω-silylacetylenic α-cyano ketone 2 in good yield (Scheme ). , …”