Enantioselective 1,3-Dipolar Cycloaddition Reaction of Nitrones with α-(Acyloxy)acroleins Catalyzed by Dipeptide-Derived Chiral Tri- or Diammonium Salts

Organoammonium salts of dipeptide-derived chiral tri-amines or diamines with TfOH catalyzed the enantioselective 1,3-dipolar cycloaddition reactions of alpha-acyloxyacroleins with nitrones to give the corresponding adducts in good yields (up to 96%) and with high diastereo- and enantioselectivities (up to 89% ee). Although alpha-(p-methoxybenzoyloxy)acrolein is rather unstable under the reaction conditions, alpha-(3-pyrroline-1-carbonyloxy)acrolein is stable enough to be smoothly converted into the corresponding adducts with the aid of the chiral organoammonium salt catalysts

Thioureas as Highly Active Catalysts for Biomimetic Bromocyclization of Geranyl Derivatives

Thioureas bearing electron-deficient aryl groups show high catalytic activity in the biomimetic bromocyclization of geranyl derivatives. The reaction of geranyl derivatives with N-bromosuccinimide (NBS) proceeds rapidly in CH2Cl2 to give the corresponding bromocyclization products in high yields as a ca. 1:1 mixture of endo- and exo-isomers. The reactivity of geranyl derivatives highly depends on the terminal substituent: electron-donating substituents increase the reactivity, while electron-withdrawing substituents decrease the reactivity

Annulative coupling of vinylboronic esters: aryne-triggered 1,2-metallate rearrangement

A stereoselective annulative coupling of a vinylboronic ester ate-complex with arynes producing cyclic borinic esters has been developed. An annulation reaction that proceeded through the formation of two C-C bonds and a C-B bond was realized by exploiting a 1,2-metallate rearrangement of boronate triggered by the addition of a vinyl group to the strained triple bond of an aryne. The generated aryl anion would then cyclize to a boron atom to complete the annulation cascade. The annulated borinic ester could be converted to boronic acids and their derivatives by oxidation, halogenation, and cross-coupling. Particularly, halogenation and Suzuki-Miyaura coupling proceeded in a site-selective fashion and produced highly substituted alkylboronic acid derivatives

Formal Total Synthesis of Manzacidin B via Sequential Diastereodivergent Henry Reaction

A formal total synthesis of manzacidin B is described. beta,beta-Disubstituted gamma-hydroxy-beta-aminoalcohol, the key structure of manzacidin B, is stereoselectively constructed via sequential Henry reactions. By taking advantage of noncovalent interactions, such as intramolecular hydrogen bonding and chelation, we could diastereodivergently control the stereoselectivity of the Henry reaction

Review Article : Feudalism or Absolute Monarchism?

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68809/2/10.1177_009770049001600304.pd

Hg(OTf)2-catalyzed direct vinylation of tryptamines and versatile applications for tandem reactions

We have developed a unique catalytic protocol for direct gem-vinylation of tryptamine derivatives employing Hg(OTf)2 as the optimum catalyst. The intermolecular vinylations with a series of aromatic acetylenes proceeded under ambient temperature at the C2 positions of indoles with high functional group tolerance. Based on the mechanistic insights, we further developed the tandem reactions successfully constructing a quaternary center

Biogenetically inspired synthesis and skeletal diversification of indole alkaloids

To access architecturally complex natural products, chemists usually devise a customized synthetic strategy for constructing a single target skeleton. In contrast, biosynthetic assembly lines often employ divergent intramolecular cyclizations of a polyunsaturated common intermediate to produce diverse arrays of scaffolds. With the aim of integrating such biogenetic strategies, we show the development of an artificial divergent assembly line generating unprecedented numbers of scaffold variations of terpenoid indole alkaloids. This approach not only allows practical access to multipotent intermediates, but also enables systematic diversification of skeletal, stereochemical and functional group properties without structural simplification of naturally occurring alkaloids. Three distinct modes of [412] cyclizations and two types of redox-mediated annulations provided divergent access to five skeletally distinct scaffolds involving iboga-, aspidosperma-, andranginine- and ngouniensine-type skeletons and a non-natural variant within six to nine steps from tryptamine. The efficiency of our approach was demonstrated by successful total syntheses of (+/-)-vincadifformine, (+/-)-andranginine and (2)-catharanthine

Synthesis of Highly Functionalized Decalins via Metallacycle-Mediated Cross-Coupling

Bridged bicyclic metallacyclopentenes generated from the [4 + 2] cycloaddition of metallacyclopentadienes with alkenes have been proposed as reactive intermediates in the course of [2 + 2 + 2] annulation reactions. Recently a collection of alkoxide-directed Ti-mediated [2 + 2 + 2] annulation reactions have been discovered for the synthesis of densely functionalized hydrindanes, where the bridged bicyclic metallacyclopentenes from intramolecular [4 + 2] were treated as fleeting intermediates en route to cyclohexadiene products formed by formal cheletropic extrusion of Ti­(O<i>i</i>-Pr)₂. In studies aimed at understanding the course of these organometallic cascade reactions it was later discovered that these bridged bicyclic intermediates can be trapped by various elimination processes. Here, we have realized metallacycle-mediated annulation reactions for the assembly of angularly substituted decalinsstructural motifs that are ubiquitous in natural products and molecules of pharmaceutical relevance. In addition to defining the basic annulation reaction we have discovered a surprising stability associated with the complex organometallic intermediates generated in the course of this coupling process and document here the ability to control the fate of such species. Ligand-induced cheletropic extrusion of the titanium center delivers cyclohexadiene-containing products, while several distinct protonation events have been identified to realize polycyclic products that contain three new stereocenters (one of which is the angular quaternary center that is a hallmark of alkoxide-directed titanium-mediated [2 + 2 + 2] annulation reactions). Examples of this metallacycle-mediated annulation reaction are provided to demonstrate that a range of stereodefined fused bicyclo­[4.4.0]­decanes are accessible, including those that contain aromatic and aliphatic substituents, and an empirical model is presented to accompany the observations made