Synthesis of (–)-Indolizidine 167B based on domino hydroformylation/cyclization reactions

Abstract

The synthesis of (-)-Indolizidine 167B has been achieved from optically active (R)-3-(pyrrol-1-yl)hex-1-ene. The key step is a highly regioselective hydroformylation reaction and a one-pot intramolecular cyclization providing a general approach to the indolizine nucleus.

Enantioselective synthesis of chiral α,α-dialkyl indoles and related azoles by cobalt-catalyzed hydroalkylation and regioselectivity switch

“…Chiral α,α -dialkyl pyrrole 3aa obtained by our method can be converted to compound 5 through halogenation and elimination. 5 is the key intermediate for the asymmetric synthesis of (-)-Indolizidine 167B 62 . Chiral α,α -dialkyl carbazole 3y obtained by our method can be used as a conducting monomer and subsequently polymerized into a conducting polymer for electrochemical studies (Fig.…”

Reductive Alkylation of Tertiary Lactams via Addition of Organocopper (RCu) Reagents to Thioiminium Ions

“…Application of the developed method for the synthesis of (±)-indolizidine 167B, a natural product isolated from the skin of the frog Dendrobates speciosus, − was examined next (Scheme ). − Reaction of the thioiminium 1 with the organocopper reagent derived from the protected bromoketone 20 , easily prepared from commercial 4-bromobutanoyl chloride in two steps, , afforded the desired 2-substituted pyrrolidine 21 in 80% yield. Remarkably, the use of an organocopper species derived from an organomagnesium reagent is fully compatible with our reaction sequence.…”

Synthesis of indolizidines from optically pure α‐amino acids via stereocontrolled rhodium‐catalyzed hydroformylation of N‐allylpyrroles

“…20,21 During the last few years, the oxo process also has been used in the synthesis of fine chemicals especially integrated in multistep domino reaction sequences, which are a very convenient approach to complex architectures in one simple, safe, environmentally acceptable, and resource-effective operation. [22][23][24][25] The mechanistic as well as synthetic implications of the oxo reaction involving vinyl and allyl aromatic and heteroaromatic olefins have been a topic of our research for many years; [26][27][28][29][30][31] in this case, the rhodium-catalyzed hydroformylation is used by us in the total synthesis of target compounds 32,33 and as a key reaction in a domino process. All reaction sequences are stereocontrolled; indeed, the chiral center in the starting amino acid is transferred into 5,6-dihydroindolizine moiety with complete stereochemical integrity, and the new stereogenic center at C9 carbon atom in the final indolizidines is generated in only one configuration.…”