Stereoselective tetrapyrido[2,1-a]isoindolone synthesis via carbanionic and radical intermediates: a model study for the Tacaman alkaloid D/E ring fusion

Abstract

Cyclization under both radical and carbanionic conditions of N-substituted 3-phenylsulfanylisoindolin-1-one 14 containing a chiral N-tether incorporating an enoate ester as the acceptor leads to tetrahydropyrido[2,1-a]isoindolones stereoselectively. The major product 17 from carbanionic cyclization was stereoselectively desulfurized with nickel boride allowing correlation of cyclization products from both methodologies. The cyclization stereoselectivities have been rationalised using a transition-state model in which the acceptor grouping adopts a pseudoaxial configuration. This contrasts with other 6-exo-trig processes in which a pseudoequatorial configuration is normally adopted, and has been attributed to the steric influence imposed by the bulky tert-butyldiphenylsilyloxy chiral auxiliary allylic to the enoate ester. The product stereochemistries provide models for the required cis-stereochemistry of the D/E ring fusion of the Tacaman alkaloid skeleton via the relatively unexplored C-3-C-14 bond disconnection.

Pyrone Diels–Alder Routes to Indolines and Hydroindolines: Syntheses of Gracilamine, Mesembrine, and Δ7‐Mesembrenone

“…This outcome suggests that the α,β‐unsaturated system of putative intermediate 52 had been reduced prior to reclosure of the ring. The identity of 55 was confirmed by its conversion, in two further steps, into 56 , a side product Gao and co‐workers had also prepared and whose 1 H NMR data were in full agreement with our synthetic material.…”

Pyrone Diels–Alder Routes to Indolines and Hydroindolines: Syntheses of Gracilamine, Mesembrine, and Δ7‐Mesembrenone

“…In this process we believe that 51 is initially formed, with subsequent elimination and reattack of the amine onto the resultant Michael system of 52 affording the needed cis-fusion in the hydroindoline core; [25] over the time course of the reaction, the resultant ketone is then reduced to afford 53,amaterial which, for purposes of full characterization, was oxidized with pyridinium dichromate (PDC) to afford 54 in 39 %y ield. Theidentity of 55 was confirmed by its conversion, in two further steps,i nto 56, [27] as ide product Gao and co-workers had also prepared and whose 1 HNMR data [4b] were in full agreement with our synthetic material. [26] This outcome suggests that the a,b-unsaturated system of putative intermediate 52 had been reduced prior to reclosure of the ring.…”

“…[26] This outcome suggests that the a,b-unsaturated system of putative intermediate 52 had been reduced prior to reclosure of the ring. Theidentity of 55 was confirmed by its conversion, in two further steps,i nto 56, [27] as ide product Gao and co-workers had also prepared and whose 1 HNMR data [4b] were in full agreement with our synthetic material.…”

Thiols, thioethers, and related compounds as sources of C-centred radicals

“…215,216 The presence of an electron-withdrawing group at the olefin terminus allowed a clean 6-exo-cyclization affording a tetrahydropyrido[2,1-a]isoindolone without formation of the non-cyclized desulfurized product (Scheme 95). [217][218][219] In this case, a relatively high concentration of tin hydride was tolerated (slow addition over only 10 minutes).…”