Diastereoselective Synthesis of Thieno(3',2':4,5)cyclopenta(1,2-d)(1,3)-oxazolines-New Ligands for the Copper-Catalyzed Asymmetric Conjugate Addition of Diethylzinc to Enones

Several new ligands featuring a rigid three ring skeleton have been prepared for the first time following a modular approach. Chirality has been introduced by use of an oxazoline moiety fused with a cyclopenta[b]thiophene backbone. The efficiency and stereochemical impact of these ligands on the copper-catalyzed enantioselective addition of Et2Zn to chalcone was examined and enantiomeric excesses up to 79% were achieved using the ligand (R,R)-16 substituted with a methyl group at the cyclopenta moiety. Computational and ESI-mass spectral studies show that these new compounds behave as monodentate ligands towards Cu+. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)

[1]  A. Voituriez,et al.  Synthesis of new sulfur-containing oxazoline ligands and their use in palladium-catalyzed allylic substitution , 2003 .

[2]  C. Senanayake,et al.  Asymmetric synthesis of conformationally constrained cis-1-amino-1-phenylcyclohexan-2-ol , 1996 .

[3]  J. Christoffers,et al.  Synthesis of chiral tridentate oxazolines with thioether and heteroaryl donor groups and their application in the catalysis of asymmetric Michael reactions , 1999 .

[4]  H. Mizutani,et al.  Cu-catalyzed asymmetric conjugate additions of alkylzinc reagents to acyclic aliphatic enones. , 2002, Journal of the American Chemical Society.

[5]  Xinmiao Liang,et al.  Nonlinear effects in the enantioselective 1,4-conjugate addition of diethylzinc to chalcone , 2003 .

[6]  R. Moriarty,et al.  Direct α-hydroxylation of ketones using iodosobenzene , 1981 .

[7]  R. Kellogg,et al.  Sulfur derivatives of ephedra alkaloids; new and highly efficient chiral catalysts. , 1994 .

[8]  A. Becke.  A New Mixing of Hartree-Fock and Local Density-Functional Theories , 1993 .

[9]  P. Darke,et al.  L-735,524: the design of a potent and orally bioavailable HIV protease inhibitor. , 1994, Journal of medicinal chemistry.

[10]  O. Reiser,et al.  New applications of bis(oxazoline) ligands in catalysis: asymmetric 1,2- and 1,4-addition of ZnR(2) to carbonyl compounds. , 2001, Organic letters.

[11]  J. Eames,et al.  Investigations on the Efficiency of Regioselective C‐Deuteration of Endocyclic Enolates , 2002 .

[12]  N. Re,et al.  Density Functional Study of the Reppe Carbonylation of Acetylene , 2000 .

[13]  D. M. Grove,et al.  Arenethiolatocopper(I) Complexes as Homogeneous Catalysts for Michael Addition Reactions , 1994 .

[14]  M. Shipman,et al.  Asymmetric Michael additions to .alpha.,.beta.-unsaturated oxazolines. An efficient preparation of chiral .beta.,.beta.-disubstituted propionaldehydes , 1991 .

[15]  P. Maitlis,et al.  Tetramethylthiophen complexes of rhodium, iridium, palladium, and ruthenium , 1978 .

[16]  C. Rosini,et al.  Catalytic enantioselective conjugate addition of dialkyl zinc reagents to α,β-unsaturated ketones mediated by new phosphite ligands containing binaphthalene/1,2-diphenylethane moieties: a practical synthesis of (R)-(−)-muscone , 2003 .

[17]  Cesarotti,et al.  2,2',5,5'-tetramethyl-4,4'-bis(diphenylphoshino)-3,3'-bithiophene: a new, very efficient, easily accessible, chiral biheteroaromatic ligand for homogeneous stereoselective catalysis , 2000, The Journal of organic chemistry.

[18]  V. Wendisch,et al.  Enantioselective copper(I) catalyzed 1,4-addition of diethylzinc to cyclohexenone: asymmetric induction as an unexpected source of structural information , 1997 .

[19]  F. Bernardi,et al.  Theoretical Study of the Mechanism of Carbonyl Insertion Reactions Catalyzed by Nickel Complexes , 2000 .

[20]  P. Ettmayer,et al.  Inhibitors of human immunodeficiency virus type 1 protease containing 2-aminobenzyl-substituted 4-amino-3-hydroxy-5-phenylpentanoic acid: synthesis, activity, and oral bioavailability. , 1996, Journal of medicinal chemistry.

[21]  H. Vorbrüggen,et al.  A simple synthesis of Δ2-oxazines, Δ2-oxazines, Δ2-thiazolines and 2-substituted benzoxazoles , 1993 .

[22]  Dennis R. Salahub,et al.  Optimization of Gaussian-type basis sets for local spin density functional calculations. Part I. Boron through neon, optimization technique and validation , 1992 .

[23]  A. Riera,et al.  A Purely Synthetic, Diversity Amenable Version of Norephedrine Thiols for the Highly Enantioselective Diethylzinc Addition to Aldehydes , 2001 .

[24]  A. Alexakis,et al.  Enantioselective Copper-Catalysed Conjugate Addition , 2002 .

[25]  B. E. Rossiter,et al.  Asymmetric conjugate addition , 1992 .

[26]  M. Foster,et al.  Bistratamides C and D. Two new oxazole-containing cyclic hexapeptides isolated from a Philippine Lissoclinum bistratum ascidian , 1992 .

[27]  A. Cantu,et al.  Novel synthesis of thianinhydrin , 1997 .

[28]  H. Stoll,et al.  Energy-adjustedab initio pseudopotentials for the second and third row transition elements , 1990 .

[29]  J. Howard,et al.  Chiral ferrocenyl-oxazolines incorporating thioether units: effective ligands for palladium-catalysed allylic substitution , 1997 .

[30]  Hai‐Feng Zhou,et al.  Highly enantioselective copper-catalyzed conjugate addition of diethylzinc to enones using chiral spiro phosphoramidites as ligands. , 2003, The Journal of organic chemistry.

[31]  J. Fiaud,et al.  Dibenzothiophene-bis(oxazolines): new sulfur-containing ligands tested in asymmetric palladium-catalyzed allylic substitutions , 2002 .

[32]  P. Cozzi,et al.  Effective modular iminooxazoline (IMOX) ligands for asymmetric catalysis: [Zn(IMOX)]-promoted enantioselective reduction of ketones by catecholborane. , 2003, Angewandte Chemie.

[33]  A. Alexakis,et al.  Asymmetric conjugate addition of diethyl zinc to enones with chiral phosphorus ligands derived from TADDOL , 1998 .

[34]  C. Frost,et al.  Enantioselective palladium catalysed allylic substitution with sulfur-containing oxazoline ligands , 1993 .

[35]  G. Varchi,et al.  Synthesis and Reactivities of Enantiomerically Pure β‐Hydroxyalkyl and β‐Aminoalkyl Ferrocenyl Sulfides , 2002 .

[36]  B. Feringa,et al.  Enantioselective Catalytic Conjugate Addition of Dialkylzinc Reagents using Copper-Phosphoramidite Complexes; Ligand Variation and Non-linear Effects , 2000 .

[37]  Alicia P. Higueruelo,et al.  A DFT computational study of the bis-silylation reaction of acetylene catalyzed by palladium complexes. , 2002, Journal of the American Chemical Society.

[38]  B. Feringa,et al.  Highly Enantioselective Catalytic Conjugate Addition and Tandem Conjugate Addition–Aldol Reactions of Organozinc Reagents , 1997 .

[39]  Qi‐Lin Zhou,et al.  Chiral mercaptoaryl-oxazolines as ligands in enantioselective copper-catalyzed 1,4-additions of Grignard reagents to enones , 1994 .

[40]  L. Giordano,et al.  Cyclopenta[b]thiophene-alkyloxazolines: new nitrogen-sulfur hybrid ligands and their use in asymmetric palladium-catalyzed allylic alkylation , 2004 .

[41]  R. Kellogg,et al.  Chiral nonracemic pyridine thiols and thioethers applied in palladium-catalyzed allylic substitution. An example of near-perfect enantioselection , 1998 .

[42]  D. Widdowson,et al.  Silyl Group Migration in 2-(Trialkylsilyl)thiophenetricarbonylchromium(0) Complexes , 1992 .

[43]  D. Berta,et al.  Chiral sulfoxides and sulfides tethered to pyridines as ligands for enantioselective catalysis: Palladium catalyzed allylic substitution and addition of diethylzinc to benzaldehyde , 1997 .

[44]  I. Escher,et al.  New Chiral Oxazoline-Phosphite Ligands for the Enantioselective Copper-Catalyzed 1,4-Addition of Organozinc Reagents to Enones , 2000 .

[45]  R. Hulst,et al.  Thiol and disulfide derivatives of ephedra alkaloids 2: A mechanistic study of their effect on the addition of diethyl zinc to benzaldehyde , 1995 .

[46]  A. Alexakis,et al.  Dramatic improvement of the enantiomeric excess in the asymmetric conjugate addition reaction using new experimental conditions. , 2002, Journal of the American Chemical Society.

[47]  J. S. Johnson,et al.  Chiral bis(oxazoline) copper(II) complexes: versatile catalysts for enantioselective cycloaddition, Aldol, Michael, and carbonyl ene reactions. , 2000, Accounts of chemical research.

[48]  B. Feringa,et al.  Diastereoselective synthesis of pyridyl substituted thiazolidin-4-ones. New ligands for the Cu(I) catalyzed asymmetric conjugate addition of diethylzinc to enones , 1997 .

[49]  M. Lavin,et al.  Structure-activity relationships of the lissoclinamides: cytotoxic cyclic peptides from the ascidian Lissoclinum patella. , 1990, Journal of medicinal chemistry.

[50]  Geis,et al.  A modular approach to structurally diverse bidentate chelate ligands for transition metal catalysis , 2000, Chemistry.

[51]  C. Gibson.  Catalytic enantioselective conjugate additions using enantiopure β-amino disulfides and β-amino thiolates , 1996 .

[52]  J. Christoffers,et al.  Novel Diamino and Diimino Thioethers – Chiral Tridentate Ligands for Asymmetric Michael Reactions? , 1999 .

[53]  M. Frisch,et al.  Ab Initio Calculation of Vibrational Absorption and Circular Dichroism Spectra Using Density Functional Force Fields , 1994 .

[54]  A. Meyers,et al.  3 – Asymmetric Synthesis via Chiral Oxazolines , 1984 .

[55]  Arun K. Ghosh,et al.  C 2-Symmetric chiral bis(oxazoline)-metal complexes in catalytic asymmetric synthesis. , 1998, Tetrahedron, asymmetry.

[56]  C. Frost,et al.  Enantioselective palladium catalysed allylic substitution with thienyl oxazoline ligands , 1993 .

[57]  S. Rajaram,et al.  Modular synthesis of amine-functionalized oxazolines. , 2002, Organic letters.

[58]  A. Hird,et al.  Cu-catalyzed enantioselective conjugate additions of alkyl zinc reagents to unsaturated N-acyloxazolidinones promoted by a chiral triamide phosphane. , 2003, Angewandte Chemie.