手性氨基醇在不对称催化中的应用及新进展

综述了手性氨基醇作为配体或催化剂在不对称合成中的应用及最新进展。     

A Highly anti‐Selective Asymmetric Henry Reaction Catalyzed by a Chiral Copper Complex: Applications to the Syntheses of (+)‐Spisulosine and a Pyrroloisoquinoline Derivative

A highly anti‐selective asymmetric Henry reaction has been developed, affording synthetically versatile β‐nitroalcohols in a predominately anti‐selective manner (mostly above 15:1) and excellent ee values (mostly above 95 %). Moreover, the anti‐selective Henry reaction was carried out in the presence of water for the first time with up to 99 % ee. The catalytic mechanism was proposed based on the detection of the intermediates by extractive electrospray ionization mass spectrometry (EESI‐MS). Furthermore, the anti adducts have been successfully transformed into the biochemically important (+)‐spisulosine and a pyrroloisoquinoline derivative.     

Acyclic chiral amines and amino acids as inexpensive and readily tunable catalysts for the direct asymmetric three-component Mannich reaction

The direct three-component asymmetric Mannich reaction catalyzed by acyclic chiral amines or amino acids is presented. Simple acyclic chiral amines and amino acids--such as alanine-tetrazole (9), alanine, valine, and serine-catalyzed the three-component asymmetric Mannich reactions between unmodified ketones, p-anisidine, and aldehydes with high chemo- and stereoselectivity, furnishing the corresponding Mannich bases with up to >99 % ee. This study demonstrates that the whole range of amino acids in nature, as well as nonproteogenic amino acid derivatives, can be considered in the design and tuning of novel, inexpensive organocatalysts for the direct asymmetric Mannich reaction.     

Asymmetric diethyl- and diphenylzinc additions to aldehydes by using a fluorine-containing chiral amino alcohol: a striking temperature effect on the enantioselectivity, a minimal amino alcohol loading, and an efficient recycling of the amino alcohol

A chiral pyrrolidinylmethanol derivative containing perfluoro-ponytails (5) was prepared from (S)-proline. The use of this perfluoro-substituted amino alcohol in catalytic asymmetric additions of organozinc reagents to aldehydes affords products with high enantioselectivities in both pure hexane and a mixture of hexane and FC-72 (perfluorohexane). Enantiomeric excesses up to 94 and 88 % ee have been achieved in Et(2)Zn and Ph(2)Zn additions, respectively. For the reactions in the biphasic solvent system a striking temperature effect was observed. Thus, when the temperature was raised from 0 to 40 degrees C the ee value of the product increased from 81 to 92 %. Furthermore, the catalyst loading could be remarkably low, and with only 0.1 mol % of amino alcohol 5 a product with 90 % ee was obtained in the Et(2)Zn addition to benzaldehyde in hexane. The perfluoro-ligand was easily recovered by simple phase separation, and until the ninth repetition its reuse proceeded without significant loss of enantioselectivity and reactivity.     

Highly Enantioselective Zinc/Amino Alcohol‐Catalyzed Alkynylation of Aldehydes

Meeting the challenge : The zinc/amino alcohol catalyzed enantioselective addition of terminal alkynes to aldehydes is effective with both phenylacetylene and methyl propiolate, leading to chiral secondary propargyl alcohols with very high enantioselectivity (see scheme).

     

Highly enantioselective ruthenium-catalyzed reduction of ketones employing readily available Peptide ligands

Highly efficient and selective catalysts for the asymmetric reduction of aryl alkyl ketones under hydrogen-transfer conditions (2-propanol) were obtained by combining a novel class of pseudo-dipeptide ligands with [[RuCl(2)(p-cymene)](2)]. A library of 36 dipeptide-like ligands was prepared from N-Boc-protected alpha-amino acids and the enantiomers of 2-amino-1-phenylethanol and 1-amino-2-propanol. The catalyst library was evaluated with the reduction of acetophenone and excellent enantioselectivity of 1-phenylethanol was obtained with several of the novel catalysts. A ligand based on the combination of N-Boc-L-alanine and (S)-1-amino-2-propanol (ligand A-(S)-4) was found to be particular effective. When the situ formed ruthenium complex of this ligand was employed as the catalyst in the hydrogen-transfer reaction of various aryl alkyl ketones, the corresponding alcohol products were achieved in excellent enantioselectivity (up to 98 % ee).