Stereoselective polymerization of racemic lactide (rac-LA) was examined using Al-achiral ligand complexes. By introduction of substituents in aromatic rings of Schiff base ligands, a higher selectivity was obtained without any chiral auxiliaries in the catalyst via a chain-end control mechanism. The T(m) values (T(m) 170-192 degrees C) were comparable to or higher than that of homochiral polymer, poly(L-LA) (T(m) 162 degrees C), and a thermally more stable polylactide than poly(L-LA) was prepared from rac-LA.

Electron-donating group-substituted 2-iodoxybenzoic acids (IBXs) such as 5-Me-IBX (1g), 5-MeO-IBX (1h), and 4,5-Me(2)-IBX (1i) were superior to IBX 1a as catalysts for the oxidation of alcohols with Oxone (a trademark of DuPont) under nonaqueous conditions, although Oxone was almost insoluble in most organic solvents. The catalytic oxidation proceeded more rapidly and cleanly in nitromethane. Furthermore, 2-iodoxybenzenesulfonic acid (IBS, 6a) was much more active than modified IBXs. Thus, we established a highly efficient and selective method for the oxidation of primary and secondary alcohols to carbonyl compounds such as aldehydes, carboxylic acids, and ketones with Oxone in nonaqueous nitromethane, acetonitrile, or ethyl acetate in the presence of 0.05-5 mol % of 6a, which was generated in situ from 2-iodobenzenesulfonic acid (7a) or its sodium salt. Cycloalkanones could be further oxidized to alpha,beta-cycloalkenones or lactones by controlling the amounts of Oxone under the same conditions as above. When Oxone was used under nonaqueous conditions, Oxone wastes could be removed by simple filtration. Based on theoretical calculations, we considered that the relatively ionic character of the intramolecular hypervalent iodine-OSO(2) bond of IBS might lower the twisting barrier of the alkoxyperiodinane intermediate 16.

On the basis of Woodward-Hoffmann frontier molecular orbital interactions and steric interactions between dienes and dienophiles during the formation of [2+4] pericyclic transition states, endo/exo selectivity in the Diels-Alder reaction strongly depends on the substrates.[1] Therefore, it is quite difficult to control both enantioselectivity [2] and anomalous endo/exo selectivity by conventional chiral catalysts, which can discriminate only the enantiofaces of the dienophiles. For example, in the reaction between cyclopentadiene (1) and acrolein (2 a), an endo preference is observed with regard to second-order orbital interactions without significant steric interactions [Eq. (1)]. In sharp contrast, in the reaction between 1 and an a-substituted acrolein (R ¼ 6 H), such as methacrolein (2 b), an exo preference is observed with regard to steric interactions between the methylene moiety of 1 and the substituent R at the a position of the dienophile [Eq. (2)]. Therefore, enantiomerically enriched endo-3 a and exo-3 b have been synthesized by using many conventional chiral catalysts.[2] Moreover, thermodynamically more stable and enantiomerically enriched exo-3 a can be generated by the epimerization of endo-3 a [Eq. (1)]. Alternatively, catalystinduced anomalous exo-selective Diels-Alder reactions that contravene the endo rule have been performed by Yamamoto and co-workers [3] in a non-asymmetric manner, and later by Maruoka and co-workers, [4] Sibi et al., [5] and Hayashi et al. [6] in an asymmetric manner. In contrast, enantiomerically enriched endo-3 b with a quaternary carbon center can not be generated by the epimerization of exo-3 b or by other known synthetic methods [Eq. (2)]. To the best of our knowledge, no examples of catalyst-induced anomalous endo-selective enantioselective Diels-Alder reactions with a-substituted acroleins have been reported to date. To address this major yet unexplored subject, catalysts must discriminate chiral transition-state structures by precisely recognizing the re or si face of dienophiles, and the endo or exo approach of dienes, thus, the rational design of conformationally flexible chiral supramolecular catalysts, such as enzymes, is necessary. [7] As such, conformationally rigid metal-organic frameworks (MOFs) are not suitable as artificial enzymes because they have few induced-fit properties to adapt dynamics in transition states. [8] A chiral supramolecular catalyst (4 a) was readily prepared in situ from three components, which included 10 mol % of chiral (R)-3,3'-bis(5,5-dimethyl-2-oxido-1,3,2-dioxaphosphorinan-2-yl)-BINOL (5 a; BINOL = 1,1'-bi(2-naphthol)), [9] 10 mol % of 3,5-bis(trifluoromethyl)phenylboronic acid (6 a), and 20 mol % of tris(pentafluorophenyl)borane (7), by taking advantage of the typical preparation of boron BINOLates [10] (Scheme 1). Intermolecular acid-base coordinate bonds in the two P=O···B(C 6 F 5 ) 3 moieties [11] are critical for the design of conformationally flexible complex 4 a; compound 7 acts as a bulky functional group to form a ch...

We have designed a minimal artificial metalloenzyme that is prepared in situ from Cu(OTf) 2 or Cu(NTf 2) 2 (1.0 equiv) and L-DOPA-derived monopeptide (1.1 equiv) based on the cation-pi attractive interaction between copper(II) and the aromatic arm of the ligand, which is postulated on the basis of X-ray diffraction analysis and theoretical calculations. This catalyst (2-10 mol %) is highly effective for not only the enantioselective Diels-Alder reaction with alpha,beta-unsaturated 1-acyl-3,5-dimethylpyrazoles but also the enantioselective Mukaiyama-Michael reaction with these compounds. Products bearing a 3,5-dimethylpyrazolyl auxiliary may be transformed into a range of carboxylic acid derivatives, such as the corresponding carboxylic acids, esters, amides, alcohols, aldehydes, ketones, and beta-ketoesters, by known methods. The present results demonstrate that monopeptides are chirally economical and readily tunable ligands compared to bis(oxazoline)s, which have been reported to be notably useful ligands in various enantioselective reactions with bidentate electrophiles.

BBr3-chiral phosphoric acid complexes are highly effective and practical Lewis acid-assisted Brønsted acid (LBA) catalysts for promoting the enantioselective Diels-Alder (DA) reaction of α-substituted acroleins and α-CF3 acrylate. In particular, the DA reaction of α-substituted acroleins with 1,2-dihydropyridines gave the corresponding optically active isoquinuclidines with high enantioselectivities. Moreover, transformations to the key intermediates of indole alkaloids, catharanthine and allocatharanthine, are demonstrated.

From a practical point of view, the development of a novel approach for the asymmetric synthesis of both enantiomeric products through catalytic asymmetric transformations with the same chiral catalyst would be very useful.[1] Various types of chiral metal complexes have already been introduced. [2] However, strictly speaking, many of these examples have employed a distinct three-dimensional association between a chiral ligand and different metals, or vice versa. In marked contrast, an initial effort for the synthetic application of chiral organocatalysts has appeared very recently, but has not been developed to a synthetically useful level. [3] In this context, we explored the capability of an additive to induce an unexpected inversion in catalyst selectivity for certain asymmetric transformations catalyzed by a single chiral organocatalyst. Herein we present the first practical example of such a system, employing achiral, organic acids as reliable additives in asymmetric, direct aldol reactions catalyzed by a chiral, cisdiamine-based, Tf-amido organocatalyst of type 1 (Tf = trifluoromethanesulfonyl Scheme 1). [4][5][6][7] Initally, the asymmetric direct aldol reaction of cyclohexanone and a-keto ester 3 a was carried out with organocatalyst 1 a to establish the optimum reaction conditions. The treatment of cyclohexanone 2 a and a-keto ester 3 a with 20 mol % of 1 a in methanol at 0 8C gave the corresponding aldol products 4 a in moderate yields; the major isomer, syn-4 a, was obtained with high enantioselectivity (Table 1, entry 1). We had previously observed a remarkable enhancement in enantioselectivity for the asymmetric conjugate addition of heterosubstituted aldehydes to vinyl sulfones by using bulky benzoic acid additives under the influence of a structurally rigid, trans-diamine-based, Tf-amide catalyst with a dihydroanthracene framework. [8] This finding prompted us to test a series of benzoic acid derivatives to probe their potential for the reversal of enantioselectivity in these products as well. [a]Entry Additive [b] Yield [c] [%] d.r. [d] (syn/anti) aldol ee [e] [%]

The 1,2-diamine (vicinal diamine) motif is present in a number of natural products with interesting biological activity and in many chiral molecular catalysts. The efficient and stereocontrolled synthesis of enantioenriched vicinal diamines is still a challenge to modern chemical methodology. We report here both syn- and anti-selective asymmetric direct Mannich reactions of N-protected aminoacetaldehydes with N-Boc-protected imines catalyzed by proline and the axially chiral amino sulfonamide (S)-3. This organocatalytic process represents the first example of a Mannich reaction using Z- or Boc-protected aminoacetaldehyde as a new entry of α-nitrogen functionalized aldehyde nucleophile in enamine catalysis. The obtained optically active vicinal diamines are useful chiral synthons as exemplified by the formal synthesis of (-)-agelastatin A.

This communication describes the rational design of an l-histidine-derived minimal artificial acylase. Our new artificial acylase, tert-butyldiphenylsilyl ether of N-(2,4,6-triisopropylbenzenesulfonyl)-pi(Me)-l-histidinol, is a simple and small molecule (molecular weight = 660) that contains only one chiral carbon center that originates from natural l-histidine. The kinetic acylation of racemic secondary alcohols induced by this compound showed an S (kfast/kslow) value of up to 93. A reusable polystyrene-bound artificial acylase was also developed to examine its practical usability.