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Divergent total syntheses of isobatzellines A/B and batzelline A were accomplished. A fully substituted common indole intermediate bearing C-2 methylthio and C-5 chloro groups was constructed via ring expansion of benzocyclobutenone oxime sulfonate with NaSMe and a benzyne-mediated cyclization/functionalization sequence as the key steps. The total synthesis of isobatzelline B was achieved via formation of the iminoquinone structure by the redox-neutral acid-promoted C-5 proto-dechlorination of the common indole intermediate. The total syntheses of isobatzelline A and batzelline A were completed in a divergent manner by oxidation of the common indole intermediate using MnO 2 or Mn(OAc) 3 , respectively.

Total synthesis of (-)-lepadiformine A featuring construction of the 1-azaspiro[4.5]decane skeleton by a highly diastereoselective radical translocation-cyclization reaction of a γ-lactam derivative bearing a chiral butenolide moiety is described. The enantioselective construction of butenolide is conducted via Krische's catalytic asymmetric allylation protocol. After the radical translocation-cyclization reaction, a hydroxymethyl group at the C-13 position was stereoselectively introduced by a one-pot partial reduction-allylation protocol of the unprotected lactam derivative. Finally, the total synthesis is completed by formation of a C ring.

An indole synthesis via ring expansion of benzocyclobutenone oxime sulfonate was developed. Utility of the indole synthesis was demonstrated by the total synthesis of (+)-CC-1065. The middle and right segments were constructed by a sequential ring expansion of the symmetrical benzo-bis-cyclobutenone. The left segment was also constructed via ring expansion of the methyl-substituted benzocyclobutenone oxime sulfonates. After condensation of these three segments, the dienone cyclopropane structure was formed to complete the total synthesis.

A multicomponent domino reaction involving three mechanistically distinct Tf 2 NH-catalyzed reactions was developed. The reaction cascade enables the assembly of a skewed 5/6/4 tricyclic motif with migration of the reactive site with the assistance of a catalyst. The tricyclic product was used to achieve the first total synthesis of cytotoxic paesslerin A by regioselective C-H insertion of the sulfonyl carbenoid and base-promoted olefin isomerization. Our results led to the revision of the originally proposed tricyclic structure of paesslerin A.

An N-linked indole structure was constructed on the 3a-position of pyrroloindoline derivatives via a cascade process involving silver-mediated amination of bromopyrroloindolines with 2-ethynylanilines with subsequent 5- endo-dig cyclization. In this reaction, AgNTf 2 was used as a tandem reagent, which activated the bromo group as a σ-Lewis acid and the alkyne moiety as a π-Lewis acid. Switching from the initial step to the second step was conducted by controlling the temperature. This protocol was applied to the synthesis of various pyrroloindolines, α-carboline, and furoindolines and the total synthesis of a dimeric indole alkaloid, (+)-pestalazine B.

A protocol for the allylation at the C3a-position of hexahydropyrroloindole using allylsilanes is developed. AgNTf 2 proved to be an efficient activator of halopyrroloindoline substrates. This method is applicable to the introduction of various allyl groups including the reverse prenyl group. The utility of this reaction is demonstrated by total synthesis of amauromine alkaloids. Stepwise bromocyclizations of the bis-indolylmethyl diketopiperazine derivative and subsequent double reverse prenylation furnished (+)-novoamauromine and (-)-epiamauromine.

A novel synthesis of substituted pyrroles by a gold(I)-catalyzed cascade reaction has been developed. The reaction proceeded with an autotandem catalysis consisting of an initial addition of gold-acetylide to an acetal moiety and was followed by gold-catalyzed 5-endo-dig cyclization and aromatization. Gold catalysts play a dual role in activating nucleophilicity or electrophilicity of terminal acetylenes by forming gold-acetylides or by π-coordination. The formal (3 + 2) annulation of two components provided a variety of substituted pyrroles in a modular fashion.

The oxidative functionalization of the benzylic C-H bonds in tetrahydroisoquinolines and tetrahydro-β-carboline derivatives was investigated. C-C bond forming reactions proceeded with a range of nucleophiles (nitroalkane, enol silyl ether, indole, allylstannane, and tetrabutylammonium cyanide) under metal-free conditions and an oxygen atmosphere. Acetic acid caused a significant acceleration effect.

Total syntheses of leuconodine B, melodinine E, and leuconoxine were accomplished via a divergent route. The [5.5.6.6]diazafenestrane skeleton was constructed from an indole-3-acetamide derivative via DMDO oxidation to hydroxylindolenine, TMSOTf/2,6-lutidine mediated cyclic aminal formation, and diastereoseletive ring-closing metathesis of a triene derivative.

A benzyne-mediated synthesis of substituted indolines and carbazoles was developed. The reaction includes generation of benzyne using Mg(TMP)2·2LiCl as a base, cyclization, and trapping the resulting organomagnesium intermediate with an electrophile to provide a series of substituted indolines and carbazoles in a regiospecific manner. This was applied to a concise five-pot total synthesis of heptaphylline.

A concise total synthesis of (-)-mersicarpine from a known cyclohexanone was accomplished. The azepinoindole core was constructed by a DIBAL-H-mediated reductive ring-expansion reaction of oxime.

The enantioselective total synthesis of (-)- and (+)-petrosin is described. The union of two key segments was executed by Suzuki-Miyaura coupling. The quinolizidine rings were stereoselectively constructed via a diastereoselective Mannich reaction and an aza-Michael reaction. The 16-membered ring was constructed by ring-closing metathesis with the second-generation Grubbs catalyst.

An improved synthesis of the indole unit, a key intermediate for eudistomin C, was established utilizing Makosza's indole synthesis. A concise total synthesis of eudistomin E was achieved on the basis of the improved synthesis.

A total synthesis of (-)-kainic acid starting from the commercially available 2-azetidinone is described. The key delta-lactone intermediate was concisely prepared from the commercially available azetidinone through the Reformatsky-type reaction and an introduction of a glycine moiety. The construction of the functionalized pyrrolidine ring was executed by a one-pot sequential elimination-Michael addition protocol of a beta-amino-delta-lactone intermediate with high diastereoselectivity.

A synthetic route to vinblastine and its analogues with an ethynyl group, which features a stereoselective coupling of an 11-membered key intermediate with vindoline, is described. Transformations of the alkynyl moiety including a partial reduction as well as a Sonogashira coupling furnished a variety of analogues.

[reaction: see text] A stereocontrolled total synthesis of (-)-kainic acid is described. A fully functionalized trisubstituted pyrrolidine ring was constructed by ring-closing metathesis of an acrylate derivative followed by an intramolecular Michael addition of the resultant alpha,beta-unsaturated lactone with high diastereoselectivity. Two alternative protocols for the construction of the alpha,beta-unsaturated lactone were also developed.

[reaction: see text] A stereocontrolled total synthesis of (-)-kainic acid is described. cis-3,4-Disubstituted pyrrolidine ring was constructed by [3 + 2] cycloaddition of azomethine ylide with chiral butenolide. The crucial introduction of carboxyl group at the C-2 position was executed by regio- and stereoselective lithiation of the pyrrolidine ring in the presence of a (+)-sparteine surrogate followed by trapping with carbon dioxide.