Binolam-AlCl: a two-centre catalyst for the synthesis of enantioenriched cyanohydrin O-phosphates

The enantioselective synthesis of cyanohydrin O‐phosphates by using in situ generated bifunctional catalysts (R)‐ or (S)‐3,3′‐bis(diethylaminomethyl)‐1,1′‐binaphthol–aluminium chloride (binolam–AlCl) is reported. The reaction, which can be described as an overall cyano‐O‐phosphorylation of aldehydes, has a wide scope and applicability. Evidence is also provided, including ab initio and DFT calculations, in support of supported by the Lewis acid/Brønsted base (LABB) dual role of the catalyst in inducing first the key enantioselective hydrocyanation, which is then followed by O‐phosphorylation. A brief screening of the synthetic usefulness of the resulting cyanohydrin O‐phosphates unveiles some interesting applications. Among them, chemoselective hydrolysis, reduction and palladium‐catalysed nucleophilic allyl substitution, thereby leading to enantiomerically enriched α‐O‐phosphorylated α‐hydroxy esters, β‐amino alcohols and γ‐cyanoallyl alcohols, respectively. Naturally occurring (?)‐tembamide and (?)‐aegeline are synthesised accordingly.     

Convenient route to enantiopure aryl cyclopentanes via Diels-Alder reaction of asymmetric dienes. Total synthesis of (+)-herbertene and (+)-cuparene

A general route for the synthesis of highly substituted aryl cyclopentanes has been developed involving Diels-Alder reaction of asymmetric dienes prepared from (+)-camphoric acid followed by aromatization of the resulting cyclohexene derivatives. Employing this protocol enantiospecific synthesis of (+)-herbertene and (+)-cuparene has been accomplished.     

Mechanistic investigation of the 2,5-diphenylpyrrolidine-catalyzed enantioselective alpha-chlorination of aldehydes

The mechanism for the 2,5-diphenylpyrrolidine-catalyzed enantioselective alpha-chlorination of aldehydes with electrophilic halogenation reagents has been investigated by using experimental and computational methods. These studies have led us to propose a mechanism for the reaction that proceeds through an initial N-chlorination of the chiral catalyst-substrate complex, followed by a 1,3-sigmatropic shift of the chlorine atom to the enamine carbon atom. The suggested reaction course is different from previously proposed mechanisms for organocatalytic enamine reactions, in which the carbon-electrophile bond is formed directly. Furthermore, the rate-determining step in the overall reaction was determined and the presence of nonlinear effects was probed.     

Employing the structural diversity of nature: development of modular dipeptide-analogue ligands for ruthenium-catalyzed enantioselective transfer hydrogenation of ketones

A library of novel dipeptide-analogue ligands based on the combination of tert-butoxycarbonyl(N-Boc)-protected alpha-amino acids and chiral vicinal amino alcohols were prepared. These highly modular ligands were combined with [[RuCl(2)(p-cymene)](2)] and the resulting metal complexes were screened as catalysts for the enantioselective reduction of acetophenone under transfer hydrogenation conditions using 2-propanol as the hydrogen donor. Excellent enantioselectivity of 1-phenylethanol (up to 98 % ee) was achieved with several of the novel catalysts. Although most of the ligands contained two stereocenters, it was demonstrated that the absolute configuration of the product alcohol was determined by the configuration of the amino acid part of the ligand. Employing ligands based on L-amino acids generated S-configured products, and catalysts based on D-amino acids favored the formation of the R-configured alcohol. The combination N-Boc-L-alanine and (R)-phenylglycinol (Boc-L-Ab) or its enantiomer (N-Boc-D-alanine and (S)-phenylglycinol, Boc-D-Aa) proved to be the best ligands for the reduction process. Transfer hydrogenation of a number of aryl alkyl ketones were evaluated and excellent enantioselectivity, up to 96 % ee, was obtained.     

Asymmetric Reductive Alkylation of Alanylproline by the Ethyl Esters of 4-Substituted 2-Oxobutenoic Acids

A method was developed for the synthesis of N-[1-(S)-(ethoxycarbonyl)-3-phenylpropyl]alanylproline (enalapril) by reductive alkylation of alanylproline with ethyl 2-oxo-4-phenylbutenoate under the conditions of hydrogenation in the presence of palladium black and 1.6% Pd/C. The yield of enalapril amounted to 65%. With the ethyl ester of the -oxo acid the diastereoselectivity of formation of the S,S,S-diastereomer was higher than with the saturated synthon. It is assumed that with ethyl 2-oxo-4-phenylbutenoate as synthon a conformationally restricted surface complex is formed between the unsaturated synthon and the active centers of the catalyst. During reductive alkylation of alanylproline by ethyl 2-oxo-4-(2-thienyl)butenoate poisoning of the catalyst occurs.     

Stereoselective synthesis of (−)-microcarpalide

A highly convergent and efficient synthesis of (−)-microcarpalide, a 10-membered lactone displaying remarkable microfilament disrupting activity is described. Ring-closing metathesis and Sharpless asymmetric dihydroxylations are the key steps. Our strategy highlights the application of novel hydroxy lactone precursors for the stereoselective synthesis of (−)-microcarpalide.     

Asymmetric synthesis of heteroorganic analogs of natural products. 6. (S)-α-amino-ω-phosphonocarboxylic acids

Alkylation, by -haloalkylphosphonates, of the Ni(II) complex of the Schiff base formed from glycine and (S)-2-N-(N¹-benzylprolyl)-o-aminobenzophenone has been used for the asymmetric synthesis of (S)-2-amino-4-phosphonobutyric and (S)-2-amino-5-phosphonovaleric acids.Institute of Bioorganic Chemistry and Oil Chemistry, Ukrainian Academy of Sciences, 250800 Kiev. A. N. Nesmeyanov Institute of Organometallic Compounds, Russian Academy of Sciences, 117813 Moscow. Translated from Izvestiya Akademii Nauk, Seriya Khimicheskaya, No. 2, pp. 397–402, February, 1992.     

A Novel Asymmetric Synthesis of （-）-cis-1, 3-Dibenzylhexahydrofuro[3, 4-d]imidazole-2,4-dione

(-)-cis-1, 3-Dibenzyl-hexahydrofuro[3, 4-d]imidazole-2, 4-dione was prepared by a new synthesis method from meso dicarboxylic acid and dehydroabietylamine by asymmetric reduction in good yield with up to 91.6% e.e. value.     

In the golden age of organocatalysis

The term "organocatalysis" describes the acceleration of chemical reactions through the addition of a substoichiometric quantity of an organic compound. The interest in this field has increased spectacularly in the last few years as result of both the novelty of the concept and, more importantly, the fact that the efficiency and selectivity of many organocatalytic reactions meet the standards of established organic reactions. Organocatalytic reactions are becoming powerful tools in the construction of complex molecular skeletons. The diverse examples show that in recent years organocatalysis has developed within organic chemistry into its own subdiscipline, whose "Golden Age" has already dawned.     

Enantioselective Oxidation of Sulfides Catalyzed by Chiral MoV and CuII Complexes of Catechol-Appended β-Cyclodextrin Derivatives in Water

The two modified β-cyclodextrin (β-CD) derivatives having catechol-type ligand (2,3- and 3,4-dihydroxy groups on the benzoate ring) were synthesized. The chiral catalytic activity of their Mo^V and Cu^II complexes was examined in the asymmetric oxidation of aromatic sulfides using hydrogen peroxide in water (pH 6.0). The oxidation with the Mo^V complexes of two β-CD derivatives were more accelerated than that with the Cu^II complexes. The sign of the optical rotation of the sulfoxides obtained in the above two cases showed the opposite configuration in the oxidation of the same sulfide. The difference of the enantioselectivity appeared also between the two complexes of the 2,3- and 3,4-dihydroxybenzoate derivatives with the same metal ion. While the use of the Mo^V complexes with the catechol derivatives yielded the sulfoxides with 35–65% ee, the use of the Cu^II complexes gave the products with the␣opposite configuration at 26–52% ee. The chiral induction in the oxidation, observed conversely between the␣catalysts, was reflected on the chiral conformation of the respective metal catalysts, showed in Induced Circular Dichroism (ICD) spectra. The highest optical yield, 65%, was observed in the oxidation of butyl phenyl sulfide using the catalytic amount (0.1 equiv) of the Mo^V complex with mono-6-O-(3,4-dihydroxybenzoyl)-β-CD. The reaction gave predominantly the (S)-sulfoxide in 95% chemical yield.