Enantioselective Synthesis of α-Quaternary Mannich Adducts by Palladium-Catalyzed Allylic Alkylation: Total Synthesis of (+)-Sibirinine

A catalytic enantioselective method for the synthesis of α-quaternary Mannich-type products is reported. The two-step sequence of (1) Mannich reaction followed by (2) decarboxylative enantioselective allylic alkylation serves as a novel strategy to in effect access asymmetric Mannich-type products of “thermodynamic” enolates of substrates possessing additional enolizable positions and acidic protons. Palladium-catalyzed decarboxylative allylic alkylation enables the enantioselective synthesis of five-, six-, and seven-membered ketone, lactam, and other heterocyclic systems. The mild reaction conditions are notable given the acidic free N–H groups and high functional group tolerance in each of the substrates. The utility of this method is highlighted in the first total synthesis of (+)-sibirinine.

[1]  B. Trost,et al.  Palladium-catalyzed decarboxylative asymmetric allylic alkylation of enol carbonates. , 2009, Journal of the American Chemical Society.

[2]  J. Aubé,et al.  Reactions of Alkyl Azides and Ketones as Mediated by Lewis Acids: Schmidt and Mannich Reactions Using Azide Precursors , 2000 .

[3]  B. Stoltz,et al.  Expanding insight into asymmetric palladium-catalyzed allylic alkylation of N-heterocyclic molecules and cyclic ketones. , 2013, Chemistry.

[4]  M. Sodeoka,et al.  Pd(II)-Catalyzed asymmetric addition reactions of 1,3-dicarbonyl compounds: Mannich-type reactions with N-Boc imines and three-component aminomethylation. , 2008, Chemistry, an Asian journal.

[5]  A. Zwierzak,et al.  An expeditious one-pot synthesis of diethyl N-Boc-1-aminoalkylphosphonates , 2002 .

[6]  Z. Shao,et al.  Enantioselective palladium-catalyzed decarboxylative allylation of carbazolones: total synthesis of (-)-aspidospermidine and (+)-kopsihainanine A. , 2013, Angewandte Chemie.

[7]  D. Enders,et al.  Efficient Regio‐ and Enantioselective Mannich Reactions , 1996 .

[8]  D. Grierson,et al.  Asymmetric synthesis XV : enantiospecific synthesis of (+) and (−) isonitramines from a common chiral intermediate , 1988 .

[9]  B. Stoltz,et al.  Enantioselective construction of α-quaternary cyclobutanones by catalytic asymmetric allylic alkylation. , 2013, Angewandte Chemie.

[10]  Kiyoshi Matsumoto,,et al.  Mannich Reaction Under High Pressee. Dimethylaminomethylation of Ketones with bis(Diyethylamino)methane under Mild Conditions , 1984 .

[11]  E. Nakamura,et al.  Synthesis of Chiral α‐Fluoroketones through Catalytic Enantioselective Decarboxylation , 2005 .

[12]  Yohan Park,et al.  Highly enantioselective total synthesis of (+)-isonitramine. , 2012, Organic letters.

[13]  C. Barbas,et al.  Asymmetric Synthesis of Quaternary α- and β-Amino Acids and β-Lactams via Proline-Catalyzed Mannich Reactions with Branched Aldehyde Donors , 2004 .

[14]  S. Danishefsky,et al.  Regioselective mannich reactions via trimethylsilyl enol ethers , 1980 .

[15]  V. Puranik,et al.  Enantioselective Total Syntheses of (–)-Isonitramine, (–)-Sibirine, and (+)-Nitramine by Ring-Closing Metathesis , 2011 .

[16]  M. Tramontini.  Advances in the Chemistry of Mannich Bases , 1973 .

[17]  Nathaniel H. Sherden,et al.  Enantioselective decarboxylative alkylation reactions: catalyst development, substrate scope, and mechanistic studies. , 2011, Chemistry.

[18]  A. Córdova,et al.  Direct Catalytic Enantioselective α‐Aminomethylation of Ketones , 2004 .

[19]  Michael Arend,et al.  Modern Variants of the Mannich Reaction. , 1998, Angewandte Chemie.

[20]  M. Sodeoka,et al.  Catalytic asymmetric addition of beta-ketoesters to various imines by using chiral palladium complexes. , 2005, Angewandte Chemie.

[21]  Marie-Christine Lallemand,et al.  Expeditious Enantioselective Biomimetic Synthesis of the Nitraria Alkaloids (+)‐Isonitramine and (−)‐Sibirine , 1998 .

[22]  A. Córdova.  The direct catalytic asymmetric mannich reaction. , 2004, Accounts of chemical research.

[23]  H. Mukherjee,et al.  Rapid synthesis of an electron-deficient t-BuPHOX ligand: cross-coupling of aryl bromides with secondary phosphine oxides. , 2010, Tetrahedron letters.

[24]  B. Stoltz,et al.  Enantioselective Construction of Quaternary N-Heterocycles by Palladium-Catalyzed Decarboxylative Allylic Alkylation of Lactams , 2011, Nature chemistry.

[25]  B. Stoltz,et al.  Deracemization of quaternary stereocenters by Pd-catalyzed enantioconvergent decarboxylative allylation of racemic beta-ketoesters. , 2005, Angewandte Chemie.

[26]  J. Poirier,et al.  Synthesis of racemic nitramine, isonitramine and sibirine , 2005 .

[27]  J. Fossey,et al.  Catalytic enantioselective formation of C-C bonds by addition to imines and hydrazones: a ten-year update. , 2011, Chemical reviews.

[28]  L. Angiolini,et al.  Further advances in the chemistry of mannich bases , 1990 .

[29]  J. Tsuji,et al.  Palladium Reagents and Catalysts: New Perspectives for the 21st Century , 2005 .

[30]  B. Stoltz,et al.  PREPARATION OF (S)-2-Allyl-2-methylcyclohexanone (Cyclohexanone, 2-methyl-2-(2-propen-1-yl)-, (2S)-). , 2009, Organic syntheses; an annual publication of satisfactory methods for the preparation of organic chemicals.

[31]  P. Maulik,et al.  A short formal synthesis of three epimers of penmacric acid , 2010 .

[32]  M. Shibasaki,et al.  Direct catalytic asymmetric Mannich reaction of unmodified ketones: Cooperative catalysis of an AlLibis(binaphthoxide) complex and La(OTf)3·nH2O , 1999 .

[33]  K. Ishihara,et al.  Chiral lithium(I) binaphtholate salts for the enantioselective direct Mannich-type reaction with a change of syn/anti and absolute stereochemistry. , 2010, Journal of the American Chemical Society.

[34]  B. Trost,et al.  Asymmetric allylic alkylation of cyclic vinylogous esters and thioesters by Pd-catalyzed decarboxylation of enol carbonate and beta-ketoester substrates. , 2006, Angewandte Chemie.

[35]  S. Schaus,et al.  Highly diastereoselective asymmetric Mannich reactions of 1,3-dicarbonyls with acyl imines. , 2006, Organic letters.

[36]  Yonghong Deng,et al.  Active Site Design in a Chemzyme: Development of a Highly Asymmetric and Remarkably Temperature-Independent Catalyst for the Imino Aldol Reaction. , 2001, Angewandte Chemie.

[37]  K. R. Knudsen,et al.  A chiral molecular recognition approach to the formation of optically active quaternary centres in aza-Henry reactions. , 2005, Organic & biomolecular chemistry.

[38]  D. Lupton,et al.  Enantioselective palladium-catalyzed decarboxylative allylation of carbazolones and indolones: formal synthesis of (+)-kopsihainanine A. , 2013, Angewandte Chemie.