Enantioselective Construction of Vicinal Stereogenic Quaternary Centers by Dialkylation: Practical Total Syntheses of (+)- and meso-Chimonanthine

All three stereoisomers of the hexacyclic 3a,3a'-bispyrrolidino[2,3-b]indoline moiety found in complex indole alkaloids can be prepared, as illustrated by total syntheses of meso-chimonanthine (1) and (+)-chimonanthine (2). A rare example of high diastereoselectivity arising from the combination of a prostereogenic enolate with a chiral electrophile containing a sp(3) carbon atom is the key feature of the asymmetric synthesis of the C(2) stereoisomer.     

A Divergent Synthetic Route to the Vallesamidine and Schizozygine Alkaloids: Total Synthesis of (+)‐Vallesamidine and (+)‐14,15‐Dehydrostrempeliopine

The total synthesis of representative members of the schizozygine alkaloids, (+)‐vallesamidine and (+)‐14,15‐dehydrostrempeliopine, were completed from a late‐stage divergent intermediate. The synthesis took advantage of efficient nitro‐group reactions with the A/B/C ring skeleton constructed concisely on a gram scale through an asymmetric Michael addition, nitro‐Mannich/lactamisation, Tsuji–Trost allylation, and intramolecular C?N coupling reaction. Other key features of the synthesis are a novel [1,4] hydride transfer/Mannich‐type cyclisation to build ring E and a diastereoselective ring‐closing metathesis reaction to construct ring D. This approach gave access to a late‐stage C14,C15 alkene divergent intermediate that could be simply transformed into (+)‐vallesamidine, (+)‐14,15‐dehydrostrempeliopine, and potentially other schizozygine alkaloids and unnatural derivatives.     

Enantioselective Total Syntheses of (−)‐Rhazinilam, (−)‐Leucomidine B,and (+)‐Leuconodine F

A divergent total synthesis of three structurally distinct natural products from imine 9 was accomplished through an approach featuring: 1) a Pd‐catalyzed decarboxylative cross‐coupling, and 2) heteroannulation of 9 with bromoacetaldehyde and oxalyl chloride to give tetrahydroindolizine 6 and dioxopyrrole 7 , respectively. The former was converted into (−)‐rhazinilam, while the latter was converted into (−)‐leucomidine B and (+)‐leuconodine F. A substrate‐directed highly diastereoselective reduction of a sterically unbiased double bond by using a homogeneous palladium catalyst was developed. A self‐induced diastereomeric anisochronism (SIDA) phenomenon was observed for leucomidine B.     

Enantioselective Pd‐Catalyzed Allylic Alkylation Reactions of Dihydropyrido[1,2‐a]indolone Substrates: Efficient Syntheses of (−)‐Goniomitine, (+)‐Aspidospermidine,and (−)‐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 (−)‐goniomitine, along with divergent formal syntheses of (+)‐aspidospermidine and (−)‐quebrachamine, are reported herein.