Towards the Sarpagine-Ajmaline-Macroline Family of Indole Alkaloids: Enantioselective Synthesis of an N-Demethyl Alstolactone Diastereomer.

the strategy involving the use of functionalized tetrahydro-6H-cycloocta[b]indol-6-one is reported as a key intermediate for synthesis of members of the sarpagine-ajmaline-macroline family of monoterpene indole alkaloids. The desired tricycle was synthesized through the following key steps: 1) Evans' syn-selective aldolization; 2) Liebeskind-Srogl cross-coupling using the phenylthiol ester of 3-chloropropanoic acid as a surrogate of acrylic thioester for the synthesis of 2,3-disubstituted indoles; and 3) ring-closing metathesis (RCM) for the formation of the eight-membered ring. An N-allylation followed by intramolecular 1,4-addition was planned for synthesis of the vobasine class of natural products.

Keteniminium Salts: Reactivity and Propensity toward Electrocyclization Reactions.

A predictive computational study was conducted in order to assess the efficiency of electrocyclization reactions of keteniminium salts, in an effort to form a variety of heterocyclic systems, namely, 3-amino(benzo)thiophenes, 3-amino(benzo)furans, 3-aminopyrroles, as well as 3-aminoindoles. A density functional theory (DFT) approach was utilized and the effect of heteroatoms (NMe, O, S) was thoroughly investigated by means of population analysis, QTAIM, NICS, ACID, and local reactivity descriptors (Parr and Fukui functions). The electrocyclization of enamines leading to 3-aminopyrroles was shown to be both kinetically and thermodynamically most favorable.

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.