Unveiling reliable catalysts for the asymmetric nitroaldol (Henry) reaction.

The addition reaction between nitroalkanes and carbonyl compounds to yield a nitroalcohol, namely the nitroaldol or Henry reaction, has long been known. It constitutes a powerful C C bond-forming process in organic chemistry, providing efficient access to valuable functionalized structural motifs such as 1,2-amino alcohols and a-hydroxy carboxylic acids. [2,3] Because the reaction is so well known, it is conceivable that significant efforts may have been devoted over the years to implement asymmetric versions of the Henry reaction. Surprisingly no significant success has been achieved until the last few of years. Stereocontrol in Henry reactions remains challenging: controlling the syn/anti stereochemistry is difficult, and the use of covalently bonded chiral auxiliaries as a general strategy has not been much developed because of the lack of suitable attaching sites in both the pronucleophile nitroalkane and the aldehyde component. Only recently, with the application of new concepts to catalyst design, have reliable catalytic systems appeared that significantly increase the current synthetic value of the Henry reaction. We highlight here the main concepts behind these developments and their impact in the field. Relatively soon after the discovery of the Mukaiyama aldol reaction in 1973, chiral metal promoters and catalysts were steadily developed, but no comparable progress followed the discovery by Seebach and Colvin in 1978 of the fluoride-catalyzed reaction of silyl nitronates and aldehydes. Only quite recently—almost 25 years later—two independent groups have developed chiral catalysts. Maruoka et al. have reported the addition of trimethylsilyl nitronates 2 to aromatic aldehydes 1 in the presence of 2 mol% of the chiral quaternary ammonium fluoride salt 4, to give 3 with anti :syn ratios usually higher than 90:10 and with more than 90% ee (Scheme 1). While poorer results are produced when aliphatic aldehydes are involved, the observed anti selectivity is explained on the basis of an acyclic extended transition-state model, which involves a chiral ammonium nitronate as the active species. In a conceptually different design of the catalytic system, Jørgensen has reported the use of bis(oxazoline)copper(ii) complexes such as 5 (20 mol%) in combination with tetrabutylammonium triphenylsilyl difluorosilicate (TBAT, 20 mol%). Again the anti adduct 3 is obtained preferentially, but in general both the yields (30–80%) and enantioselectivities (40–65% ee) are less impressive. Perhaps the most impressive advance in the area came from the development of the first metal/chiral ligand complexes that are able to promote the direct reaction between unmodified nitroalkanes and aldehydes enantioselectively. Shibasaki et al. reported the first efficient method of this type by making use of the general principle of two-center catalysis. A metal/chiral ligand complex was designed possessing two sites of opposite character, a basic site and an acidic site, each capable of independently activating in close proximity the nitro compound and the aldehyde substrate, respectively. For example, as little as 1 mol% of the secondgeneration lithium/lanthanum polymetallic catalyst (complex 9 + 1.0 mol equiv H2O + 0.9 mol equiv BuLi) can mediate the reaction between nitroalkanes 7 and aliphatic aldehydes 6 at 50/ 30 8C within about 120 h in very high diastereoand enantioselectivities (Scheme 2). Here, the syn adducts 8 are the major stereoisomers, thus complementing the silyl nitronate protocol mentioned above. More recent work by Trost et al. has revealed a novel family of dinuclear zinc complexes such as 10, which apparently function along a similar principle of cooperative activation. Thus, 5 mol% Scheme 1. Fluoride-promoted enantioselective nitroaldol reactions of silyl nitronates and aromatic aldehydes. [*] Prof. Dr. C. Palomo, Prof. Dr. M. Oiarbide, Dr. A. Mielgo Departamento de Qu%mica Org&nica I Facultad de Qu%mica Universidad del Pa%s Vasco Apdo. 1072 20080 San Sebasti&n (Spain) Fax: (+34)943-015270 E-mail: qoppanic@sc.ehu.es

[1]  F. Heaney,et al.  The Nitro Group in Organic Synthesis , 2004 .

[2]  J. Jurczak,et al.  Asymmetric nitroaldol reaction. Synthesis of taxotere side chain and (-)-bestatin using (1R)-8-phenylmenthyl glyoxylate. , 2004, The Journal of organic chemistry.

[3]  Yu‐Wu Zhong,et al.  New β-amino alcohols with a bicyclo[3.3.0]octane scaffold in an asymmetric Henry reaction , 2004 .

[4]  J. N. Johnston,et al.  Chiral proton catalysis: a catalytic enantioselective direct aza-Henry reaction. , 2004, Journal of the American Chemical Society.

[5]  Claudio Palomo,et al.  Current progress in the asymmetric aldol addition reaction. , 2004, Chemical Society reviews.

[6]  Y. Takemoto,et al.  Enantioselective aza-Henry reaction catalyzed by a bifunctional organocatalyst. , 2004, Organic letters.

[7]  P. Murphy,et al.  Synthesis and applications of C2-symmetric guanidine bases , 2003 .

[8]  R. Soengas,et al.  Transformation of D-glucose into 1D-3-deoxy-3-hydroxymethyl-myo-inositol by stereocontrolled intramolecular Henry reaction. , 2003, Organic letters.

[9]  A. Martell,et al.  Novel chiral N4S2- and N6S3-donor macrocyclic ligands: synthesis, protonation constants, metal-ion binding and asymmetric catalysis in the Henry reaction. , 2003, Organic & biomolecular chemistry.

[10]  K. Gothelf,et al.  Catalytic asymmetric Henry reactions of silyl nitronates with aldehydes. , 2003, Organic & biomolecular chemistry.

[11]  K. Doda,et al.  Designer chiral quaternary ammonium bifluorides as an efficient catalyst for asymmetric nitroaldol reaction of silyl nitronates with aromatic aldehydes. , 2003, Journal of the American Chemical Society.

[12]  B. Westermann.  Asymmetrische katalytische Aza‐Henry‐Reaktionen zu 1,2‐Diaminen und 1,2‐Diaminocarbonsäuren , 2003 .

[13]  B. Westermann.  Asymmetric catalytic aza-Henry reactions leading to 1,2-diamines and 1,2-diaminocarboxylic acids. , 2003, Angewandte Chemie.

[14]  S. Stahl,et al.  "Inverse-electron-demand" ligand substitution in palladium(0)-olefin complexes. , 2003, Journal of the American Chemical Society.

[15]  D. Ma,et al.  Diastereoselective Henry reactions of N,N-dibenzyl α-amino aldehydes with nitromethane catalyzed by enantiopure guanidines , 2002 .

[16]  O. Reiser,et al.  Activation of nitroaldol reactions by diethylzinc and amino alcohols or diamines as promoters , 2002 .

[17]  M. Kanai,et al.  Recent progress in asymmetric two-center catalysis. , 2002, Chemical communications.

[18]  D. Cahard,et al.  New insights in the search for chiral Brønsted bases. , 2002, Chemistry.

[19]  B. Trost,et al.  Effect of ligand structure on the zinc-catalyzed Henry reaction. Asymmetric syntheses of (-)-denopamine and (-)-arbutamine. , 2002, Organic letters.

[20]  Masakatsu Shibasaki,et al.  Lanthanide complexes in multifunctional asymmetric catalysis. , 2002, Chemical reviews.

[21]  K. Jørgensen,et al.  Copper-Catalyzed Enantioselective Henry Reactions of α-Keto Esters: An Easy Entry to Optically Active β-Nitro-α-hydroxy Esters and β-Amino-α-hydroxy Esters , 2002 .

[22]  Kiyoshi Matsumoto,,et al.  Diastereoselective asymmetric nitro-aldol reaction of alpha-amino aldehydes under high pressure without catalyst. , 2002, Angewandte Chemie.

[23]  B. Trost,et al.  A dinuclear Zn catalyst for the asymmetric nitroaldol (Henry) reaction. , 2002, Angewandte Chemie.

[24]  T. Ishikawa,et al.  Modified guanidines as chiral auxiliaries. , 2002, Chemistry.

[25]  Kiyoshi Matsumoto,,et al.  High pressure mediated asymmetric henry reaction of nitromethane with carbonyl compounds catalyzed by cinchona alkaloids , 2002 .

[26]  K. Jørgensen,et al.  Catalytic asymmetric Henry reactions—a simple approach to optically active β-nitro α-hydroxy esters , 2001 .

[27]  O. Reiser.  Comprehensive Asymmetric Catalysis. Vol. I —III. Edited by Eric N. Jacobsen, Andreas Pfaltz, and H. Yamamoto , 2001 .

[28]  G. Rowlands.  Ambifunctional Cooperative Catalysts , 2001 .

[29]  F. A. Luzzio,et al.  The Henry reaction: recent examples , 2001 .

[30]  N. Ono.  The nitro group in organic synthesis , 2001 .

[31]  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.

[32]  E. J. Corey,et al.  RE- UND SI-SEITEN-SELEKTIVE NITROALDOLREAKTIONEN, KATALYSIERT DURCH EIN STARRES, CHIRALES, QUARTARES AMMONIUMSALZ HOCHSTEREOSELEKTIVE SYNTHESE DES HIV -PROTEASE-INHIBITORS AMPRENAVIR (VERTEX 478) , 1999 .

[33]  E. Corey,et al.  re- and si-Face-Selective Nitroaldol Reactions Catalyzed by a Rigid Chiral Quaternary Ammonium Salt: A Highly Stereoselective Synthesis of the HIV Protease Inhibitor Amprenavir (Vertex 478). , 1999, Angewandte Chemie.

[34]  Eric N. Jacobsen,et al.  Comprehensive asymmetric catalysis , 1999 .

[35]  Fernando P. Cossío,et al.  Ab Initio Models for the Nitroaldol (Henry) Reaction , 1997 .

[36]  Yoichi M. A. Yamada,et al.  Self‐Assembly of Heterobimetallic Complexes and Reactive Nucleophiles: A General Strategy for the Activation of Asymmetric Reactions Promoted by Heterobimetallic Catalysts , 1996 .

[37]  S. Hanessian,et al.  Generation of functional diversity via nitroaldol condensations of α-aminoacid aldehydes — A new and stereocontrolled route to acyclic 1,3-diamino-2-alcohols , 1996 .

[38]  M. Shibasaki,et al.  Diastereoselective catalytic asymmetric nitroaldol reaction utilizing rare earth-Li-(R)-BINOL complex. A highly efficient synthesis of norstatine , 1994 .

[39]  C. Nájera,et al.  Enantiomerically pure guanidine-catalysed asymmetric nitroaldol reaction , 1994 .

[40]  J. Jaud,et al.  Nitroalkanes in C-C bond forming reactions : a crystal structure of a complex of a guanidine catalyst and a nitroalkane substrate , 1993 .

[41]  Masakatsu Shibasaki,et al.  Basic character of rare earth metal alkoxides. Utilization in catalytic C-C bond-forming reactions and catalytic asymmetric nitroaldol reactions , 1992 .

[42]  G. Rosini.  1.10 – The Henry (Nitroaldol) Reaction , 1991 .

[43]  N. Khiar,et al.  Synthesis of (2S,3R)-3-amino-2-hydroxy-5-methylhexanoic acid: bridging effect of potassium fluoride , 1990 .

[44]  D. Seebach,et al.  Diastereoselective Synthesis of Nitroaldol Derivatives , 1982 .

[45]  D. Seebach,et al.  Silyl nitronates: improved nitro-aldol reactions and reductive routes to 2-aminoalcohols , 1978 .