Hua-Dong Xu

Diastereoselectively Switchable Enantioselective Trapping of Carbamate Ammonium Ylides with Imines

The diastereoselectively switchable enantioselective trapping of protic carbamate ammonium ylides with imines is reported. The intriguing Rh(2)(OAc)(4) and chiral Brønsted acid cocatalyzed three-component Mannich-type reaction of a diazo compound, a carbamate, and an imine provides rapid and efficient access to both syn- and anti-α-substituted α,β-diamino acid derivatives with a high level control of chemo-, diastereo-, and enantioselectivity.

DABCO-Catalyzed 1,4-Bromolactonization of Conjugated Enynes: Highly Stereoselective Formation of a Stereogenic Center and an Axially Chiral Allene

A DABCO-catalyzed highly regio- and stereoselective syn-1,4-bromolactonization of conjugated enynes was discovered. The 1,4-addition occurred selectively over 1,2-addition for most enynes. In contrast to anti 1,2-addition to alkenes, where two adjacent stereogenic centers are created, 1,4-addition across conjugated enynes can produce a stereogenic center and an axially chiral allene simultaneously. Enynes with Z and E configurations yielded products with complementary stereochemistries at the newly generated stereogenic center and axially chiral allene. Di-, tri-, or even tetrasubstituted allenes together with lactones can be efficiently and selectively prepared from this enyne bromolactonization reaction.

Synthesis of Cyclobutenes by Highly Selective Transition-Metal-Catalyzed Ring Expansion of Cyclopropanes†

The four-membered ring is an important structural motif, present in many bioactive natural products and key intermediates in the synthesis of structurally complex targets by facile ring-opening reactions. Several selective methods have been developed for the synthesis of cyclobutanes and cyclobutenes. However, highly substituted four-memberedring natural products, such as sceptrin, welwitindolinone A, and their diverse derivatives still represent a demanding synthetic challenge, and stimulate the development of new selective methods. We wish to explore the use of cyclopropanes, for which stereoselective preparations have been well documented, as precursors for the synthesis of complex four-membered rings. Cyclopropyl carbenes, generated from thermal decomposition of diazo compounds, can undergo a rearrangement to give cyclobutenes but the thermal process requires harsh conditions, and affords low yields and poor selectivities. The profound effect of transition-metal catalysts, such as complexes of rhodium and copper, on the reactivity of metal carbenes has been widely recognized in cyclopropanations, C H insertions, and dipolar cycloadditions. We envision that transition-metal catalysts may offer unusual selectivity for the ring expansion of cyclopropyl metal carbenes to cyclobutenes. Cyclopropyl metal carbenes have been proposed as intermediates in the formation of various isomeric bicyclic cyclobutenes by cycloisomerization of tethered enynes, by the groups of Trost, Echavarren, and F.rstner with palladium, platinum, or gold catalysts (Scheme 1). Alternatively, cyclopropyl metal carbenes may derive from methylenecyclopropanes (MCPs). Monosubstituted cyclobutenes have been prepared from MCP by Shi and co-workers, using palladium(II) catalysts (Scheme 1). A mechanism involving no cyclopropyl metal carbenes was proposed by F.rstner and Aissa for the conversion of MCPs into monosubstituted cyclobutenes, catalyzed by platinum(II). Despite these elegant studies, selective synthesis of highly desirable polysubstituted cyclobutenes remains an elusive target, as many issues have arisen regarding reactivity and selectivity. Herein, we report a synthesis of poly-substituted cyclobutenes by transition-metal-catalyzed highly selective ring expansion of readily available cyclopropanes (Scheme 1). The unique chemo-, regio-, and stereoselectivity for the ring expansion of novel cyclopropyl dirhodium(II), copper(I), and silver(I) carbenes are described. We first screened a variety of transition-metal catalysts for the ring expansion of simple monosubstituted cyclopropane 1a, and observed complete conversion of diazo compound 1a into cyclobutenoate 1b in less than five minutes at ambient temperature with a range of catalysts (Table 1, entries 1–3). Notably, some of the metal catalysts known to promote the formation of the proposed cyclopropyl metal carbene intermediates from enynes or MCPs were inactive in this reaction. Electrophilic metal carbenes were presumably generated from diazo compound 1a following dissociation of dinitrogen in the presence of dirhodium(II), copper(I), or silver(I) catalysts. Ring expansion of cyclopropyl metal carbenes by a Scheme 1. Ring expansion of cyclopropyl metal carbenes to cyclobutenes by the migration of bond x or y.

Rhodium-Catalyzed Chemo- and Regioselective Cross-Dimerization of Two Terminal Alkynes

Cross-dimerization of terminal arylacetylenes and terminal propargylic alcohols/amides has been achieved in the presence of a rhodium catalyst. This method features high chemo- and regioselectivities rendering convenient and atom economical access to functionalized enynes.

Asymmetric hydroarylation of norbornene derivatives catalyzed by palladium complexes of chiral quinolinyl-oxazolines

Abstract Chiral quinolinyl-oxazolines were found to be efficient ligands in the enantioselective palladium-catalyzed Heck-type hydroarylation of norbornene and its derivatives. The ligands with a medium sized alkyl group on the oxazoline ring provided higher enantioselectivities. The presence of electron-donating substituents on the aryl iodide increased the selectivity and the yield of the reactions. The configuration of (−)-exo-2-phenylbicyclo[2.2.1]heptane has been assigned as (1R,2R).

Chiral 1,2,3,4-tetrahydroquinolinyl-oxazoline ligands for Ru-catalyzed asymmetric transfer hydrogenation of ketones

Abstract Chiral 1,2,3,4-tetrahydroquinolinyl-oxazoline compounds have been synthesized from 8-quinolinecarboxylic acid and enantiomerically pure amino alcohols using a convenient procedure. Asymmetric transfer hydrogenation of aryl ketones with the catalyst prepared in situ from [Ru( p -cymene)Cl 2 ] 2 and ligands 2 in 2-propanol in the presence of KOH, afforded the corresponding secondary alcohols in reasonable yields and up to 83% e.e.

Enantioselective Heck-type hydroarylation of norbornene with phenyl iodide catalyzed by palladium/quinolinyl-oxazolines

Abstract Enantioselective Heck-type hydroarylation of norbornene with phenyl iodide catalyzed by the palladium complex of quinolinyl-oxazolines is described. Using DMSO as the solvent and HCOOH/Et 3 N as the hydride source, exo -2-phenybicyclo[2.2.1]heptane is produced in reasonable yields and up to 74% ee.

Stereoselective Halocyclization of Alkenes With N‐Acyl Hemiaminal Nucleophiles

Halocyclization of alkenes was realized using N-acylhemiaminal nucleophiles. High diastereoselectivity could be achieved for the formation of three stereogenic centers in this halogen-mediated cyclization reaction. We also demonstrated that enantioselective bromocyclization of alkenes using N-acylhemiaminal nucleophiles was possible.

Remote substituent effect in palladium/pyridinyl-oxazolines catalyzed asymmetric allylic alkylation

Abstract The chiral ligands containing pyridinyl moieties and oxazolines bridged by disubstituted methylene 2 – 4 were prepared and they provided ee values 17–68% higher than unsubstituted analogues 1 in the palladium-catalyzed enantioselective allylic alkylation of 1,3-diphenyl-2-propenyl acetate with dimethyl malonate.

CCDC 839943: Experimental Crystal Structure Determination

Related Article: Jun Jiang, Hua-Dong Xu, Jian-Bei Xi, Bai-Yan Ren, Feng-Ping Lv, Xin Guo, Li-Qin Jiang, Zhi-Yong Zhang, Wen-Hao Hu|2011|J.Am.Chem.Soc.|133|8428|doi:10.1021/ja201589k