Deacylative Reactions: Synthetic Applications

Abstract

Herein we introduce the recent developments of a new strategy based on deacylative alkylation (DaA) reactions for the generation of quaternary stereocenters based on the in situ preparation and functionalization of enolates under very mild reaction conditions. Palladium‐catalyzed deacylative allylation and benzylation reactions of carbon nucleophiles are performed with the corresponding alcohols. This methodology has been applied to the synthesis of the calcium ion channel blocker verapamil, the antiviral (+)‐hamigeran B, several oxindole precursors of esermethole, horsfiline, physostigmine, phenserine, meso‐folicanthine, meso‐chinonanthine and the dimer cyclotriptamine alkaloids. Base‐promoted deacylative reactions enable the functionalization of 2‐oxindole enolates at the 3‐position with alkyl halides and electrophilic alkenes. In the presence of oxygen or air, 3‐hydroxy‐2‐oxindoles are prepared by deacylative oxidation. Detrifluoroacylative reactions are promoted by a base generating fluoroenolates, which can participate in aldol, Mannich and Michael reactions for the preparation of important fluorinated intermediates. Finally, palladium‐catalyzed deacylative cross‐coupling of acetyl diazoacetates and phosphonates with aryl iodides let to the formation of aryl diazoacetates and phosphonates, respectively. The same process, with 2‐iodoazoarenes and 2‐iodoaryltriazenes, gives 2H‐indazoles, which are important pharmacophores.

Palladium‐Catalyzed Asymmetric Allylic Alkylations of Colby Pro‐Enolates with MBH Carbonates: Enantioselective Access to Quaternary C−F Oxindoles

“…[1,2,6] Some successi nt his area has been achieved with the development of enantioselective electrophilic fluorination, [7] whereas the alternative approaches still represent af ormidable challenge. [8] Owingt ot he multifaceted biological properties of oxindole derivatives, an umber of research groupsh ave reported catalytic enantioselective elaboration of 3-fluorooxindole-derived enolates 1 (Scheme 1) by aldol or Mannich reactions, [9] conjugate additions [10] and allylic alkylations [11] offering efficient access to av ariety of structurally novel compounds of high biological importance.C onsistent with our long-standing interest in catalytic asymmetric synthesis of fluorine-containing compounds, [12] we wanted to develop the Colby pro-enolates of type 2 [8b, [13][14][15][16] as synthetic alternatives to the conventional fluoro-enolates. [17] In particular, we reported the design of 3fluorooxindole derived pro-enolates 2, [18] and their unusual reactivity with imines [18,19] and dialkyl azodicarboxylates.…”

Vinylogous Reactivity of Cyclic 2‐Enones: Organocatalysed Asymmetric Addition to 2‐Enals to Synthesize Fused Carbocycles

“…Initially, the keto‐esters 7 were treated with K 2 CO 3 (1 equiv) in refluxing acetone. Under these conditions, the presence of the hydroxy group on the concave face of 7 facilitated a retro‐Claisen condensation, affording lactones 11 in very good yields and with excellent optical purity ( 11 a , 11 b , 11 f , 11 g , 89–93 % yield, >99 % de, 91–97 % ee ; Scheme ). Moreover, when 7 a was treated with K 2 CO 3 followed by EtONa in refluxing EtOH, the bridged bicyclic compound 12 a (80 % yield, >99 % de; Scheme ) was obtained.…”

Vinylogous Reactivity of Cyclic 2‐Enones: Organocatalysed Asymmetric Addition to 2‐Enals to Synthesize Fused Carbocycles

“…With the aim of illustrating the versatility of the ester handle,t he next part of the investigation looked at the reactions of compounds of type 7 with bases.I nitially,t he keto-esters 7 were treated with K 2 CO 3 (1 equiv) in refluxing acetone.Under these conditions,the presence of the hydroxy group on the concave face of 7 facilitated ar etro-Claisen condensation, [15] affording lactones 11 in very good yields and with excellent optical purity (11 a,11 b,11 f,11 g,> 99 %de,(91)(92)(93)(94)(95)(96)(97)Scheme 6). Moreover,when 7a was treated with K 2 CO 3 followed by EtONa in refluxing EtOH, the bridged bicyclicc ompound 12 a (80 %y ield, > 99 %d e; Scheme 6) was obtained.…”