Demonstration of spontaneous chiral symmetry breaking in asymmetric Mannich and Aldol reactions.

Spontaneous symmetry breaking in reactive systems, known as a rare physical phenomenon and for the Soai autocatalytic irreversible reaction, might in principle also occur in other, more common asymmetric reactions when the chiral product is capable to promote its formation and an element of "nonlinearity" is involved in the reaction scheme. Such phenomena are long sought after in chemistry as a possible explanation for the biological homochirality of biomolecules. We have investigated homogeneous organic stereoselective Mannich and Aldol reactions, in which the product is capable to form H-bridged complexes with the prochiral educt, and found by applying NMR spectroscopy, HPLC analysis, and optical rotation measurements 0.3-50.8% of random product enantiomeric excess under essentially achiral reaction conditions. These findings imply a hitherto overlooked mechanism for spontaneous symmetry breaking and, hence, a novel approach to the problem of absolute asymmetric synthesis and could have also potential significance for the conundrum of homochirality.

[1]  Takehiro Ozawa,et al.  Generation of an optically active octahedral cobalt complex by a chiral autocatalysis , 1995 .

[2]  C. Barbas,et al.  A highly enantioselective amino acid-catalyzed route to functionalized α-amino acids , 2002 .

[3]  K. Tennakone.  Spontaneous breaking of the baryon-antibaryon symmetry in a non-equilibrium process , 1985 .

[4]  Sabino Veintemillas-Verdaguer,et al.  Homochirality as a consequence of thermodynamic equilibrium? , 2006, Chemistry.

[5]  D. Kondepudi,et al.  Chiral autocatalysis, spontaneous symmetry breaking, and stochastic behavior. , 2001, Accounts of chemical research.

[6]  Cristóbal Viedma Molero.  Chiral Symmetry Breaking During Crystallization: Complete Chiral Purity Induced by Nonlinear Autocatalysis and Recycling , 2005 .

[7]  Vadim A. Soloshonok Prof..  Remarkable Amplification of the Self-Disproportionation of Enantiomers on Achiral-Phase Chromatography Columns† , 2005 .

[8]  Kenso Soai,et al.  Asymmetric synthesis of pyrimidyl alkanol without adding chiral substances by the addition of diisopropylzinc to pyrimidine-5-carbaldehyde in conjunction with asymmetric autocatalysis , 2003 .

[9]  H. Quiney,et al.  Reflections on spontaneous asymmetric synthesis by amplifying autocatalysis. , 2003, Organic & biomolecular chemistry.

[10]  Thomas Buhse,et al.  Mirror-symmetry breaking in the Soai reaction: a kinetic understanding. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[11]  Sutapa Ghosh,et al.  Non-equilibrium thermodynamics of Lotka-Volterra ecosystems: Stability and evolution , 1995 .

[12]  John M. Brown,et al.  Asymmetric autocatalysis: novel structures, novel mechanism? , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[13]  V. Soloshonok,et al.  Remarkable amplification of the self-disproportionation of enantiomers on achiral-phase chromatography columns. , 2006, Angewandte Chemie.

[14]  K. Mislow,et al.  Absolute Asymmetric Synthesis: A Commentary , 2003 .

[15]  Shu-Kun Lin,et al.  Gibbs paradox of entropy of mixing: experimental facts, its rejection and the theoretical consequences , 2001 .

[16]  Christian Girard,et al.  Nonlinear Effects in Asymmetric Synthesis and Stereoselective Reactions: Ten Years of Investigation. , 1998, Angewandte Chemie.

[17]  F. Frank,et al.  On spontaneous asymmetric synthesis. , 1953, Biochimica et biophysica acta.

[18]  M. Mauksch,et al.  Evidence of asymmetric autocatalysis in organocatalytic reactions. , 2007, Angewandte Chemie.

[19]  Kenso Soai,et al.  Asymmetric autocatalysis and amplification of enantiomeric excess of a chiral molecule , 1995, Nature.

[20]  Stanley L. Miller,et al.  Organic Compound Synthes on the Primitive Eart: Several questions about the origin of life have been answered, but much remains to be studied , 1959 .

[21]  L. Vo,et al.  Enantioselective synthesis without discrete optically active additives. , 2002, Journal of the American Chemical Society.

[22]  E. Jacobsen,et al.  Asymmetric Catalytic Mannich Reactions Catalyzed by Urea Derivatives: Enantioselective Synthesis of β-Aryl-β-Amino Acids , 2002 .

[23]  D. Singleton,et al.  A few molecules can control the enantiomeric outcome. Evidence supporting absolute asymmetric synthesis using the Soai asymmetric autocatalysis. , 2003, Organic letters.

[24]  D. Kondepudi,et al.  Chiral Symmetry Breaking in Sodium Chlorate Crystallizaton , 1990, Science.

[25]  Hugues Bersini,et al.  Recycling Frank: Spontaneous emergence of homochirality in noncatalytic systems. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[26]  Cristobal Viedma,et al.  Chiral symmetry breaking during crystallization: complete chiral purity induced by nonlinear autocatalysis and recycling. , 2004, Physical review letters.

[27]  R. Delden,et al.  Absolute Asymmetric Synthesis: The Origin, Control, and Amplification of Chirality. , 1999, Angewandte Chemie.

[28]  W. Bonner.  Enantioselective autocatalysis. Spontaneous resolution and the prebiotic generation of chirality , 1994, Origins of life and evolution of the biosphere.

[29]  H. Hyuga,et al.  Complete Homochirality Induced by Nonlinear Autocatalysis and Recycling , 2003, physics/0310142.

[30]  D. Blackmond,et al.  Origins of asymmetric amplification in autocatalytic alkylzinc additions. , 2001, Journal of the American Chemical Society.

[31]  G. W. Nelson,et al.  Chiral-symmetry breaking in nonequilibrium systems , 1983 .

[32]  Richard A. Lerner,et al.  Proline-Catalyzed Direct Asymmetric Aldol Reactions , 2000 .

[33]  Zhangze,et al.  Efficient and Clean Aldol Condensation Catalyzed by Sodium Carbonate in Water , 2003 .