Showing papers by "Keiji Maruoka published in 2008"

Trans-selective asymmetric aziridination of diazoacetamides and N-Boc imines catalyzed by axially chiral dicarboxylic acid.

Abstract: Axially chiral dicarboxylic acid (R)-1d catalyzed reaction of diazoacetamides and N-Boc imines provided a novel organocatalytic means for the formation of enantiomerically enriched N-Boc protected trans aziridines.

Complete switch of product selectivity in asymmetric direct aldol reaction with two different chiral organocatalysts from a common chiral source.

Abstract: A novel approach for asymmetric synthesis of both enantiomeric aldol products has been developed by designing two different chiral organocatalysts from a readily available, protected cis-diamine compound as a common chiral source. This approach would be very useful from a practical viewpoint.

Asymmetric imino aza-enamine reaction catalyzed by axially chiral dicarboxylic acid: use of arylaldehyde N,N-dialkylhydrazones as acyl anion equivalent.

Abstract: Synthetic utility of arylaldehyde N,N-dialkylhydrazones as a practical acyl anion equivalent could be exploited for the first time in the asymmetric imino aza-enamine reaction catalyzed by axially chiral carboxylic acid.

Brønsted acid-catalyzed insertion of aryldiazoacetates to sp2 carbon-CHO bond: facile construction of chiral all-carbon quaternary center.

Abstract: Aryldiazoacetates could be formally inserted into the carbon−carbon bond of the Bronsted acid-activated aromatic and α,β-unsaturated aldehydes. Use of phenylmenthyl esters allowed the asymmetric induction at the inserted all-carbon quaternary carbon center with the excellent stereoselectivities.

Combinatorial design of simplified high-performance chiral phase-transfer catalysts for practical asymmetric synthesis of alpha-alkyl- and alpha,alpha-dialkyl-alpha-amino acids.

Abstract: A very efficient, chiral phase-transfer catalyst, (S)-2 Db, was prepared by taking advantage of the combinatorial approach from the readily available (S)-1,1'-binaphthyl-2,2'-dicarboxylic acid. This catalyst exhibited high catalytic performance (0.01-0.1 mol %) in the asymmetric alkylation of N-(diphenylmethylene)glycine tert-butyl ester and N-(p-chlorophenylmethylene)alanine tert-butyl ester relative to other chiral phase-transfer catalysts in current use. This has created a general and highly practical procedure for the enantioselective synthesis of structurally diverse natural and unnatural alpha-alkyl-alpha-amino acids as well as alpha,alpha-dialkyl-alpha-amino acids. A similar simplified catalyst, (S)-2 Fb, is also applicable to the direct asymmetric aldol reaction between glycine Schiff base and aldehydes with moderate syn selectivity and high enantioselectivity.

Syntheses of manzacidins: a stage for the demonstration of synthetic methodologies

Abstract: Manzacidins, a family of bromopyrrole alkaloids, have attracted much attention from the synthetic community due to their intriguing structures, bearing chiral tertiary and secondary stereocentres in a 1,3-relationship, and biological activities. In this article, we summarise the approaches for the preparation of manzacidins using novel synthetic methodologies. Organocatalysis and Lewis acid catalysis, as well as transition-metal catalysis, offered efficient ways to access these molecules.

Direct asymmetric iodination of aldehydes using an axially chiral bifunctional amino alcohol catalyst.

Abstract: A direct asymmetric iodination reaction of aldehydes with NIS was found to be catalyzed by the novel axially chiral bifunctional amino alcohol (S)-1d. This method represents the rare example of the catalytic and highly enantioselective synthesis of optically active α-iodoaldehydes.

Asymmetric 1,3-dipolar cycloadditions of N-benzyl and N-diphenylmethyl nitrones and alpha,beta-unsaturated aldehydes catalyzed by bis-titanium chiral Lewis acids.

Abstract: Bis-titanium chiral Lewis acids that contain two oxygen-bridged titanium centers were successfully applied to the asymmetric 1,3-dipolar cycloaddition of nitrones and alpha,beta-unsaturated aldehydes. The introduction of the diphenylmethyl group as the N substituent on the nitrones, with the aim of destabilizing the nitrone-Lewis acid complex, led to the drastic enhancement of not only the reactivity but also the enantioselectivity. By employing this approach, 1,3-dipolar cycloadditions of nitrones and the rather unreactive methacrolein were facilitated to give cycloadducts that bear one all-carbon quaternary center with unique regioselectivity and excellent stereoselectivity.

6,6'-Substituent effect of BINOL in bis-titanium chiral Lewis acid catalyzed 1,3-dipolar cycloaddition of nitrones.

Abstract: By the accommodation of modified BINOLs as chiral ligands, enantioselectivities in the bis-titanium chiral Lewis acid catalyzed 1,3-dipolar cycloaddition of N-diphenylmethyl nitrones and methacrolein could be improved.

Direct Asymmetric Aminoxylation Reaction Catalyzed by Axially Chiral Amino Acids

Abstract: Binaphthyl-based amino acids were prepared and applied for the direct asymmetric aminoxylation of aldehydes with nitrosobenzene. The reaction catalyzed by (S)-1e proceeded smoothly to give the amin...

Facile Synthesis of Structurally Diverse 3,3′-Disubstituted 1,1′-Binaphthyl-2,2′-diamines in Optically Pure Forms

Abstract: A new synthetic route to 3,3′-dihalo BINAMs based on the direct halogenation of H8-BINAM and subsequent rearomatization to the binaphthyl core has been developed. The combination of this new procedure and Pd-catalyzed coupling reactions enabled us to synthesize various 3,3′-disubstituted BINAMs in only three steps starting from H8-BINAM.

The Basic Principle of Phase‐Transfer Catalysis and Some Mechanistic Aspects

Abstract: In 1971, Starks introduced the term “phase-transfer catalysis” to explain the critical role of tetraalkylammonium or phosphonium salts (QþX ) in the reactions between two substances located in different immiscible phases [1]. For instance, the displacement reaction of 1-chlorooctane with aqueous sodium cyanide is accelerated many thousand-fold by the addition of hexadecyltributylphosphonium bromide 1 as a phase-transfer catalyst (Scheme 1.1). The key element of this tremendous reactivity enhancement is the generation of quaternary phosphonium cyanide, which renders the cyanide anion organic soluble and sufficiently nucleophilic.

Design of an Axially Chiral DicarboxylicAcid and Its Application in Syntheses of Optically Active β-AminoAcids and β-Amino Phosphonic Acid Derivatives

Abstract: An axially chiral dicarboxylic acid was developed as a new chiral Bronsted acid catalyst. With this novel catalyst in hand, N-Boc-protected p-amino acids or P-amino phosphonic acid derivatives could be obtained in high yields and enantioselectivities by asymmetric Mannich-type reaction of N-Boc imines and diazo compounds.

Complete Switch of Migratory Aptitude in Aluminum‐Catalyzed 1,2‐Rearrangement of Differently α,α‐Disubstituted α‐Siloxy Aldehydes

Abstract: Skeletal rearrangements involving 1,2-carbon-to-carbon migration are powerful methods for the structural reorganization of organic molecules, and they often make it feasible to construct otherwise hard-to-access molecular frameworks. Unsymmetrical substrates, however, generally give a mixture of structural isomers, which constitutes a major drawback of the 1,2-rearrangement and debases its synthetic utility. Thus, research into the regioselective 1,2-rearrangement to afford a single product is of practical importance. A common approach to this subject is the design of substrates based on the relative migratory aptitudes of the substituents and/or conformational effects, which often establishes selective transformation leading to the most favorable isomers. Nevertheless, this strategy requires the preparatory installation of all structural features that will drive the rearrangement in the desired direction, and, in principle, the obtainable products are restricted to just one. In contrast, intentional control of the migratory tendency for the selective synthesis of any isomer from one substrate by switching the migrating group is challenging and attractive. Even now, successful examples to address this issue are very limited. As part of our research on aluminum-mediated selective 1,2-migrations, we recently developed an enantioselective 1,2rearrangement of a,a-disubstituted a-siloxy aldehydes by using the chiral aluminum Lewis acid 1, in which a kinetic resolution of racemic, differently a,a-disubstituted a-siloxy aldehydes was also achieved. When a-siloxy aldehyde 2a was treated with 1 in toluene at 20 8C for 12 h, siloxy ketone 3a was obtained almost exclusively in 49% yield with 86% ee, along with recovered 2a (51%, 84% ee ; Scheme 1). Although the observed predominant formation of 3a is explicable by assuming selective migration of the benzyl group over the phenyl group (with subsequent transfer of the silyl group), such an interpretation is inconsistent with common understanding because the prominent migratory ability of the phenyl group has been well-documented in pinacol and Wagner–Meerwein rearrangements. This contradiction prompted us to pursue further research in a new direction in order to figure out the crucial element governing the unique regioselectivity of this reaction, which would enable the selective preparation of any isomer at will. Herein, we detail our discovery of an unprecedented regiodivergent 1,2rearrangement of differently a,a-disubstituted a-siloxy aldehydes. Our initial investigation was focused on verification of the effect of the Lewis acid catalyst on the regioselectivity in the reaction of 2a. Since the previously reported aluminum Lewis acid 1 has the two characteristic features of steric hindrance and relatively weak Lewis acidity, we first examined the impact of the bulkiness of catalyst, and the rearrangement of 2a was thus conducted with a series of sterically hindered aluminum Lewis acids (Table 1). Interestingly, the use of ATPH as a catalyst was found to provide an equimolar mixture of the two isomers, 3a and 4a (Table 1, entry 1). Whereas a similar product distribution was retained in the reaction with MABR, 3a was obtained preferentially, with a 3a/4a ratio of 5:1, when the structurally similar but less Lewis acidic MAD was employed (Table 1, entries 2 and 3). These results, particularly the distinct difference in the regioselectivity between the reactions with MABR and MAD, imply that the selectivity is influenced by the Lewis acidity of the catalyst rather than its steric size. Enhancement of the Lewis acidity might thus lead to an increase in the proportion of 4a in the rearranged products. We next performed the reactions of 2a with other catalysts to elucidate the relationship between the regioseScheme 1. 1,2-Rearrangement of the differently a,a-disubstituted a-siloxy aldehyde 2a.

Direct Asymmetric Iodination of Aldehydes Using an Axially Chiral Bifunctional Amino Alcohol Catalyst.

Abstract: A direct asymmetric iodination reaction of aldehydes with NIS was found to be catalyzed by the novel axially chiral bifunctional amino alcohol (S)-1d. This method represents the rare example of the catalytic and highly enantioselective synthesis of optically active α-iodoaldehydes.

Design of Binaphthyl-Modified Symmetrical Chiral Phase-Transfer Catalysts: Substituent Effect of 4,4′,6,6′-Positions of Binaphthyl Rings in the Asymmetric Alkylation of a Glycine Derivative.

Abstract: A series of symmetrical chiral phase-transfer catalysts with 4,4',6,6'-tetrasubstituted binaphthyl units have been designed, and these aryl- and trialkylsilyl-substituted phase-transfer catalysts, which included a highly fluorinated catalyst, were prepared. The chiral efficiency of these chiral phase-transfer catalysts was investigated in the asymmetric alkylation of tert-butylglycinate-benzophenone Schiff base under mild phase-transfer conditions, and the eminent substituent effect of the 4,4',6,6'-positions of the binaphthyl units on enantioselection was observed. In particular, the OctMe2Si-substituted catalyst was found to be highly efficient for the phase-transfer alkylation of tert-butylglycinate-benzophenone Schiff base with various alkyl halides, including sec-alkyl halides. The highly fluorinated catalyst was also utilized as a recyclable chiral phase-transfer catalyst by simple extraction with fluorous solvents.