14 research outputs found
Enantioselective palladium-catalyzed allylic alkylation reactions in the synthesis of Aspidosperma and structurally related monoterpene indole alkaloids
Enantioselective Pd-catalyzed allylic alkylations of prochiral enolates represent a powerful tool for the construction of all-carbon quaternary stereocenters. This review describes the emergence of such reactions as strategic linchpins that enable efficient, stereocontrolled syntheses of Aspidosperma and related monoterpene indole alkaloids
Enantioselective palladium-catalyzed allylic alkylation reactions in the synthesis of Aspidosperma and structurally related monoterpene indole alkaloids
Enantioselective Pd-catalyzed allylic alkylations of prochiral enolates represent a powerful tool for the construction of all-carbon quaternary stereocenters. This review describes the emergence of such reactions as strategic linchpins that enable efficient, stereocontrolled syntheses of Aspidosperma and related monoterpene indole alkaloids
Enantioselective Catalysis Coupled with Stereodivergent Cyclization Strategies Enables Rapid Syntheses of (+)-Limaspermidine and (+)-Kopsihainanine A
Enantioselective Pd-catalyzed allylic alkylations of dihydropyrido[1,2-a]indolone (DHPI) substrates were used to construct the C20-quaternary stereocenters of multiple monoterpene indole alkaloids. Stereodivergent PictetâSpengler and BischlerâNapieralski cyclization/reduction cascades furnish the cis- and trans-fused azadecalin subunits present in Aspidosperma and Kopsia alkaloids, respectively, enâ
route to highly efficient syntheses of (+)-limaspermidine and (+)-kopsihainanineâ
A
Enantioselective Pd-Catalyzed Allylic Alkylation Reactions of Dihydropyrido[1,2-a]indolone Substrates: Efficient Syntheses of (â)-Goniomitine, (+)-Aspidospermidine, and (â)-Quebrachamine
The successful application of dihydropyrido[1,2-a]indolone (DHPI) substrates in Pd-catalyzed asymmetric allylic alkylation chemistry facilitates rapid access to multiple alkaloid frameworks in an enantioselective fashion. Strategic bromination at the indole C3 position greatly improved the allylic alkylation chemistry and enabled a highly efficient Negishi cross-coupling downstream. The first catalytic enantioselective total synthesis of (â)-goniomitine, along with divergent formal syntheses of (+)-aspidospermidine and (â)-quebrachamine, are reported herein
Enantioselective Synthesis of 뱉Quaternary Mannich Adducts by Palladium-Catalyzed Allylic Alkylation: Total Synthesis of (+)-Sibirinine
A catalytic enantioselective method for the synthesis of α-quaternary Mannich-type products is reported. The two-step sequence of (1) Mannich reaction followed by (2) decarboxylative enantioselective allylic alkylation serves as a novel strategy to in effect access asymmetric Mannich-type products of âthermodynamicâ enolates of substrates possessing additional enolizable positions and acidic protons. Palladium-catalyzed decarboxylative allylic alkylation enables the enantioselective synthesis of five-, six-, and seven-membered ketone, lactam, and other heterocyclic systems. The mild reaction conditions are notable given the acidic free NâH groups and high functional group tolerance in each of the substrates. The utility of this method is highlighted in the first total synthesis of (+)-sibirinine
The Total Synthesis of (â)-Scabrolide A
The first total synthesis of the norcembranoid diterpenoid scabrolide A is disclosed. The route begins with the synthesis of two chiral pool-derived fragments, which undergo a convergent coupling to expediently introduce all 19 carbon atoms of the natural product. An intramolecular DielsâAlder reaction and an enoneâolefin cycloaddition/fragmentation sequence are then employed to construct the fused [5â6â7] linear carbocyclic core of the molecule and complete the total synthesis
Enantioselective Catalysis Coupled with Stereodivergent Cyclization Strategies Enables Rapid Syntheses of (+)-Limaspermidine and (+)-Kopsihainanine A
Enantioselective Pd-catalyzed allylic alkylations of dihydropyrido[1,2-a]indolone (DHPI) substrates were used to construct the C20-quaternary stereocenters of multiple monoterpene indole alkaloids. Stereodivergent PictetâSpengler and BischlerâNapieralski cyclization/reduction cascades furnish the cis- and trans-fused azadecalin subunits present in Aspidosperma and Kopsia alkaloids, respectively, enâ
route to highly efficient syntheses of (+)-limaspermidine and (+)-kopsihainanineâ
A
Preparation of 1,5-Dioxaspiro[5.5]undecan-3-one
A. 3-Amino-3-(hydroxymethyl)-1,5-dioxaspiro[5.5]undecane. A 1-L single-necked, round-bottomed flask is equipped with an egg-shaped, TeflonÂź-coated magnetic stirring bar (3.5 cm x 1.5 cm), capped with a rubber septum, flame-dried under vacuum, and cooled under an argon atmosphere (Note 1). After cooling to ambient temperature (21-23 °C), to the flask is added anhydrous N,N-dimethylformamide (DMF, 365 mL, 0.78 M) via cannula. Subsequently, tris(hydroxymethyl)aminomethane hydrochloride (45.0 g, 286 mmol, 1.00 equiv) (Note 2 and 3) is added in a single portion as white crystalline solid. The reaction vessel is immediately resealed with a rubber septum under inert atmosphere and stirring is commenced (Figure 1). To this white suspension is added 1,1-dimethoxycyclohexane (50.0 mL, 47.4 g, 329 mmol, 1.15 equiv) via syringe in one portion (Note 4). Lastly, to the off-white slurry is added para-toluenesulfonic acid monohydrate (p-TsOHâąH2O, 1.63 g, 8.57 mmol, 0.03 equiv) as a solid in one portion quickly, immediately replacing the rubber septum to maintain an inert atmosphere
Selective syntheses of leuconolam, leuconoxine, and mersicarpine alkaloids from a common intermediate through regiocontrolled cyclizations by Staudinger reactions
Selective syntheses of leuconolam, leuconoxine, and mersicarpine alkaloids bearing distinctive core structures were achieved through Staudinger reactions using a common intermediate. In the key cyclization step, water functioned like a switch to control which core structure to produce. The chemistry allowed for selective syntheses of the group of alkaloids from a simple intermediate through straightforward chemical operations
The Total Synthesis of (â)-Scabrolide A
The first total synthesis of the norcembranoid diterpenoid scabrolide A is disclosed. The route begins with the synthesis of two chiral pool-derived fragments, which undergo a convergent coupling to expediently introduce all 19 carbon atoms of the natural product. An intramolecular DielsâAlder reaction and an enoneâolefin cycloaddition/fragmentation sequence are then employed to construct the fused [5â6â7] linear carbocyclic core of the molecule and complete the total synthesis