Intramolecular alkene carboamination reactions for the synthesis of enantiomerically enriched tropane derivatives.

The synthesis of tropane derivatives via intramolecular Pd-catalyzed alkene difunctionalization reactions is described. Enantiopure N-aryl-γ-aminoalkenes bearing an aryl or alkenyl halide adjacent to the amino group were converted to benzo- or cycloalkenyl-fused tropane products in good yield and with no loss of enantiopurity.

[1]  J. Wolfe Palladium-Catalyzed Carboetherification and Carboamination Reactions of γ-Hydroxy- and γ-Aminoalkenes for the Synthesis of Tetrahydrofurans and Pyrrolidines. , 2007, European journal of organic chemistry.

[2]  G. Lehmann,et al.  Die Synthese des Tropinons, Pseudopelletierins, Lobelanins und verwandter Alkaloide unter physiologischen Bedingungen , 1935 .

[3]  J. Ellman,et al.  Synthesis and applications of tert-butanesulfinamide. , 2010, Chemical reviews.

[4]  J. Wolfe,et al.  Intramolecular Insertion of Alkenes into Pd−N Bonds. Effects of Substrate and Ligand Structure on the Reactivity of (P−P)Pd(Ar)[N(Ar1)(CH2)3CR═CHR′] Complexes , 2011 .

[5]  J. Wolfe,et al.  Pd-catalyzed carboamination of oxazolidin-2-ones: a stereoselective route to trans-2,5-disubstituted pyrrolidines. , 2010, Organic letters.

[6]  J. Wolfe,et al.  Palladium-catalyzed synthesis of N-aryl pyrrolidines from gamma-(N-Arylamino) alkenes: evidence for chemoselective alkene insertion into Pd--N bonds. , 2004, Angewandte Chemie.

[7]  K. Rice,et al.  Synthesis and structure-activity relationship of C5-substituted analogues of (+-)-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine [(+-)-desmethyl-MK801]: ligands for the NMDA receptor-coupled phencyclidine binding site. , 1990, Journal of medicinal chemistry.

[8]  P. Anderson,et al.  Synthesis and pharmacological evaluation of a series of dibenzo[a,d]cycloalkenimines as N-methyl-D-aspartate antagonists. , 1990, Journal of medicinal chemistry.

[9]  W. H. Pearson,et al.  Total synthesis of (+)-cocaine via desymmetrization of a meso-dialdehyde. , 2004, Organic letters.

[10]  Wai F. Wong,et al.  trans-acetonide controlled endo-selective intramolecular nitrone-alkene cycloaddition of hept-6-enoses: a facile entry to calystegines, tropanes, and hydroxylated aminocycloheptanes. , 2007, Organic letters.

[11]  H. Davies,et al.  Asymmetric synthesis of tropanes by rhodium-catalyzed [4 + 3] cycloaddition. , 2007, Journal of the American Chemical Society.

[12]  F. A. Davis,et al.  Asymmetric total synthesis of (S)-(+)-cocaine and the first synthesis of cocaine C-1 analogs from N-sulfinyl β-amino ester ketals. , 2010, Organic letters.

[13]  J. Wolfe Stereoselective Synthesis of Saturated Heterocycles via Pd-Catalyzed Alkene Carboetherification and Carboamination Reactions. , 2008, Synlett : accounts and rapid communications in synthetic organic chemistry.

[14]  Masahiro Hamada,et al.  Synthesis of Bridged Benzoazabicyclic Compounds Using Radical Translocation/Cyclization Reactions of 1-Alkynyl-2-(o-Iodobenzoyl)tetrahydroisoquinolines , 2000 .

[15]  D. Dean,et al.  Synthesis of Functionalized Azomethine Ylides via the Rh(II)-Catalyzed Cyclization of .alpha.-Diazo Carbonyls onto Imino .pi.-Bonds , 1994 .

[16]  M. Kanai,et al.  Enantioselective construction of quaternary stereocenter through a Reissert-type reaction catalyzed by an electronically tuned bifunctional catalyst: efficient synthesis of various biologically significant compounds. , 2001, Journal of the American Chemical Society.

[17]  S. Buchwald,et al.  The development of efficient protocols for the palladium-catalyzed cyclization reactions of secondary amides and carbamates. , 1999, Organic letters.

[18]  J. Wolfe,et al.  Use of aryl chlorides as electrophiles in Pd-catalyzed alkene difunctionalization reactions. , 2010, The Journal of organic chemistry.

[19]  J. Wolfe,et al.  Mild conditions for Pd-catalyzed carboamination of N-protected hex-4-enylamines and 1-, 3-, and 4-substituted pent-4-enylamines. Scope, limitations, and mechanism of pyrrolidine formation. , 2008, The Journal of organic chemistry.

[20]  G. Molander,et al.  Lanthanide-Catalyzed Hydroamination of Hindered Alkenes in Synthesis: Rapid Access to 10,11-Dihydro-5H-dibenzo- [a,d]cyclohepten-5,10-imines , 1999 .

[21]  F. Carroll,et al.  Benzyne addition to N-alkyl-4-hydroxy-1-methylisoquinolinium salts; a new and convenient synthesis of (±)-5-methyl-10,11-dihydro-5H-dibenzo-[a,d]cyclohepten-5,10-imine (MK801) , 1996 .

[22]  Patrick S. Hanley,et al.  Intermolecular insertion of ethylene and octene into a palladium-amide bond. Spectroscopic evidence for an ethylene amido intermediate. , 2010, Journal of the American Chemical Society.

[23]  C. Fu,et al.  One-pot construction of aza- or oxa-bridged benzocycloheptanes from readily available 2,3-allenyl malonates or 2,3-allenols and o-iodobenzaldehyde or imine. , 2011, Organic letters.

[24]  J. Wolfe,et al.  Intramolecular alkene aminopalladation reactions of (dppf)Pd(Ar)[N(Ar(1))(CH(2))(3)CH=CH(2)] complexes. insertion of unactivated alkenes into Pd-N bonds. , 2010, Journal of the American Chemical Society.

[25]  R. Grigg,et al.  Palladium-Catalysed CascadesTriggered by Dehydrogenation of Secondary or Tertiary Amines: Accessto Bridged- and Fused-Ring Heterocycles , 2008 .

[26]  Ji-Eun Lee,et al.  Gold-catalyzed waste-free generation and reaction of azomethine ylides: internal redox/dipolar cycloaddition cascade. , 2008, Angewandte Chemie.

[27]  K. Mikami,et al.  One-pot synthesis of tropinone by tandem (domino) ene-type reactions of acetone silyl enol ethers. , 2002, Chemical communications.

[28]  R. Reamer,et al.  .alpha.-Effect nucleophiles: a novel and convenient method for the synthesis of dibenzo[a,d]cycloheptenimines , 1988 .

[29]  K. Rice,et al.  A bridgehead α-amino carbanion: facile preparation of C5(bridgehead)-substituted analogues of (±)-5H-dibenzo[a,d]cyclohepten-5,10-imine including a stable α-iodo secondary amine , 1989 .

[30]  J. Monn,et al.  Conformational and steric aspects of the inhibition of phenylethanolamine N-methyltransferase by benzylamines. , 1988, Journal of medicinal chemistry.

[31]  J. Rung,et al.  (+)-MK-801 induced social withdrawal in rats; a model for negative symptoms of schizophrenia , 2005, Progress in Neuro-Psychopharmacology and Biological Psychiatry.

[32]  Siyang Xing,et al.  Efficient construction of oxa- and aza-[n.2.1] skeletons: Lewis acid catalyzed intramolecular [3+2] cycloaddition of cyclopropane 1,1-diesters with carbonyls and imines. , 2010, Angewandte Chemie.

[33]  S. Benetti,et al.  Synthetic approaches to enantiomerically pure 8-azabicyclo[3.2.1]octane derivatives. , 2006, Chemical reviews.

[34]  G. Grynkiewicz,et al.  Tropane alkaloids as medicinally useful natural products and their synthetic derivatives as new drugs. , 2008, Pharmacological reports : PR.

[35]  Robert Robinson,et al.  LXIII.—A synthesis of tropinone , 1917 .

[36]  R. Willstätter,et al.  Synthese des natürlichen Cocains , 1923 .

[37]  Pei‐Qiang Huang,et al.  A new method for the construction of the hydroxylated tropane skeleton: enantioselective synthesis of (-)-Bao Gong Teng A. , 2011, Chemical communications.

[38]  J. Wolfe,et al.  Intramolecular Pd-catalyzed carboetherification and carboamination. Influence of catalyst structure on reaction mechanism and product stereochemistry. , 2006, Journal of the American Chemical Society.

[39]  S. Martin Ring-closing metathesis: A facile construct for alkaloid synthesis , 2005 .