Dearomatization−Bis-alkylation of Aromatic and Heteroaromatic Diesters Promoted by Me₃SnLi via a Stanna−Brook Rearrangement

Abstract

Reaction of Me3SnLi with aromatic and heteroaromatic diesters proceeds through a fast stanna-Brook rearrangement that generates an stable bis-enolate which can be regioselectively alkylated and cyclized, in one step, to bicyclic compounds containing 6,5-, 6,6-, and 6,7-fused ring systems.

Enantioselective Annulation Reactions of Bisenolates Prepared Through Dearomatization Reactions of Aromatic and Heteroaromatic Diesters

“…When 1,4-diiodobutane was used as the electrophile under the same reaction conditions, 9b was obtained in 59 % yield. The ring-forming bisalkylation of the furan-derived bisenolate proved to be more difficult with 1,5-diiodopentane but, as observed previously with phthalate and pyridine diesters, [10] the 5,7-fused bicycle 9c was prepared, albeit in a lower yield (48 %), by warming the reaction mix-ture to 40°C. All bicyclic compounds were obtained with complete stereoselectivity, as only one stereoisomer was detected in the 1 H NMR spectra of the crude reaction mixtures (Scheme 2).…”

“…This substoichiometric procedure can also be successfully applied to heteroaromatic diesters, as thiophene 8 (X = S) provided the expected bicycle 10b in 56 % yield. Despite the fact that the yields obtained by using this catalytic procedure are slightly lower than when stoichiometric Me 3 SnLi is used, [10] we consider that the economic savings and the lower toxicity of the process make it a valuable alternative. Nevertheless, some limitations to the general applicability of this catalytic procedure were found as no reaction was observed when terephthalate and naphthalene diesters were subjected to these conditions.…”

“…The reaction mixture was stirred for 6 h while slowly warming to room temperature. Work up as for 18a and column chromatography (SiO 2 , EtOAc/hexane, 1:20) afforded the corresponding bicycles 21a [10] (90 mg, 77 %), 21b [10] (83 mg, 68 %), 22a [10] (SiO 2 , EtOAc/hexane, 1:10, 73 mg, 60 %) and 10b (neutral Al 2 O 3 , CH 2 Cl 2 /hexane, 1:1, 64 mg, 56 %).…”

“…This tandem sequence allows the stereoselective preparation of 6,5-, 6,6-and 6,7-fused carbobicyclic and heterobicyclic systems with the concomitant formation of one or two quaternary stereocentres in the process. [10] Our procedure involves the treatment of benzene and pyridine diesters with R 3 SnLi, to provide highly nucleophilic bisenolates (a process that involves a stanna-Brook rearrangement) [11] followed by trapping the intermediates with 1,ω-dihaloalkanes and related biselectrophiles. This dearomatization-alkylation procedure (Scheme 1) does not result from the nucleophilic addition of trialkylstannyllithium to the electron-deficient aromatic ring (as in many nucleophilic addition-initiated dearomatization reactions), [1a,3] but instead from 1,2-addition to a carboxylate group followed by 1,2 Li-Sn rearrangement of the initial stannyl alkoxide adduct (Scheme 1).…”

Dearomatization of Fused Arenes Using Platinum‐Catalyzed Intramolecular Formation of Two CC Bonds

“…[5] However, the catalytic formation of two CÀC bonds at the ipso and ortho or para positions of the substituent Z to produce cyclohexadienes has not been reported to date (Scheme 1, type 2). [7] Herein, we present the platinum(II)-catalyzed dearomatization of N-benzyl-N- (1-naphthyl)propiolamide derivatives through the formation of two intramolecular C À C bonds at the ipso and ortho positions of the acylamino group (Scheme 2). Several intramolecular C À C bond-forming ipso iodocyclizations of N-arylpropiolamides have been reported; [8] however, these reactions are not catalytic and did not involve the formation of two CÀC bonds.…”