Lewis acids enantioselective reactions

To the best of our knowledge the data in Table 3.2 constitute the first example of enantio selectivity in a chiral Lewis-acid catalysed organic transformation in aqueous solution. Note that for the majority of enantioselective Lewis-acid catalysed reactions, all traces of water have to be removed from the... 

Synthetic utility of stereoselective alkylations in natural product chemistry is exemplified by the preparation of optically active 2-arylglycine esters (38). Chirally specific a-amino acids with methoxyaryl groups attached to the a-carbon were prepared by reaction of the dimethyl ether of a chiral bis-lactam derivative with methoxy arenes. Using SnCl as the Lewis acid, enantioselectivities ranging from 65 to 95% were obtained. 

Catalytic asymmetric aza-Diels-Alder reactions using a chiral lanthanide Lewis acid. Enantioselective synthesis of tetrahydroquinoline derivatives using a catalytic amount of a chiral source [98]... 

The first enantioselective synthesis of cis- and trans- 3-hydroxyflavanones is based on the Lewis-acid-catalysed reaction of phenylmethanethiol with chalcone epoxides <96CC2747>. Further support for the intermediacy of epoxides in the Algar-Flynn-Oyamada flavone synthesis has been provided by the isolation of epoxides in the corresponding preparation of 3-hydroxy-2-phenylquinol-4-ones <96JCS(P2)269>. 

The highly ordered cyclic TS of the D-A reaction permits design of diastereo-or enantioselective reactions. (See Section 2.4 of Part A to review the principles of diastereoselectivity and enantioselectivity.) One way to achieve this is to install a chiral auxiliary.80 The cycloaddition proceeds to give two diastereomeric products that can be separated and purified. Because of the lower temperature required and the greater stereoselectivity observed in Lewis acid-catalyzed reactions, the best diastereoselectivity is observed in catalyzed reactions. Several chiral auxiliaries that are capable of high levels of diastereoselectivity have been developed. Chiral esters and amides of acrylic acid are particularly useful because the auxiliary can be recovered by hydrolysis of the purified adduct to give the enantiomerically pure carboxylic acid. Early examples involved acryloyl esters of chiral alcohols, including lactates and mandelates. Esters of the lactone of 2,4-dihydroxy-3,3-dimethylbutanoic acid (pantolactone) have also proven useful. 

Evans, D.A. and Tregay, S. W. and Burgey, C.S. and Paras, N.A. and Vojkovsky, T. (2000). C2-Symmetric Copper(ll) Complexes as Chiral Lewis Acids. Enantioselective Glyoxylate-Ene Reaction with Glyoxylate and Pyruvate Esters. J. Am. Chem. Soc., 122, 7936-7943. 

Chiral base catalysis was classified into five sections and reviewed. Although the reactions described herein are promoted by Bronsted or Lewis bases, the Lewis acidic characteristics of metals play important roles in both substrate activation and enantioselection. Compared with chiral Lewis acid-catalyzed reactions,... 

Stoichiometric amount of methyl aluminum p-binaphthoxide as the Lewis acid. This reaction has recently been extended to a catalytic enantioselective version using an enantiopure methylaluminum p-binaphthoxide (Scheme 11.59) (210,211). Although the actual reacting species were not assigned, 5-alkoxyoxazoles behave as nitrile ylide 1,3-dipole equivalents in Lewis acid catalyzed reactions with aldehydes. 

Formyl hydrogen bonds, in which die C—H bond of a formyl group acts as an acceptor (typically to oxygen), have recently been identified in Lewis acid-catalysed reactions of aldehydes.523 An X-ray crystal structure of such a complex has been reported.5213 This type of hydrogen bond is now suggested as a likely organizing stereochemical element in a variety of enantioselective aldol, allylation, and Diels-Alder reactions catalysed by Lewis acids reported in the literature.520 Further examples of such reactions are also discussed.53... 

The Lewis acid-catalyzed reaction of epoxides with cyanotrimethylsilane (Me3SiCN) forms /3-siloxy nitriles.252 Highly enantioselective desymmetrization of / >-epoxides with Me3SiCN can be achieved by chiral Ti and Yb catalysts (Equation (67)).255 256... 

The use of Al(III) complexes as catalysts in Lewis acid mediated reactions has been known for years. However, recent years have witnessed interesting developments in this area with the use of ingeiuously designed neutral tri-coordinate Al(lll) chelates. Representative examples involving such chelates as catalysts include (1) asymmetric acyl halide-aldehyde cyclocondensations, " (2) asymmetric Meerwein-Schmidt-Ponndorf-Verley reduction of prochiral ketones, (3) aldol transfer reactions and (4) asymmetric rearrangement of a-amino aldehydes to access optically active a-hydroxy ketones. It is important to point out that, in most cases, the use of a chelating ligand appears critical for effective catalytic activity and enantioselectivity. 

The four possible transition-state structures for the Lewis acid-promoted Diels-Alder reaction of cyclopentadiene with propynal are depicted in Fig. 7. In the chiral Lewis acid-promoted reaction, the enantiomeric excess of an adduct originates in the enantiofacial selectivity of cyclopentadiene, which has prochiral reactive centers. The enantioselective pathway presupposes three characteristics (i) the chiral Lewis acid must sterically shield one enantioface of the coordinated propynal because the open acetylenic jr-face in the chiral catalyst-dienophile complex approaches one face of... 

The Mukaiyama aldol reaction of carbonyl substrates with silyl enol ethers is the most widely accepted of Lewis acid-promoted reactions. Many Lewis acids for the reaction have been developed and used enantioselectively and diastereoselectively. In 1980, catalytic amounts of la were found by Noyori et al. to effect aldol-type condensation between acetals and a variety of silyl enol ethers with high stereoselectivity [2c,20]. Unfortunately, la has poor Lewis acidity for activation of aldehydes in Mukaiyama s original aldol reaction [21]. Hanaoka et al. showed the scope and limitation of 11-cat-alyzed Mukaiyama aldol reaction, by varying the alkyl groups on the silicon atom of silyl enol ethers [22]. Several efforts have been since been made to increase the reactivity and/or the Lewis acidity of silicon. One way to enhance the catalyst activity is to use an additional Lewis acid. 

Corey, E. J., Lee, T. W. The formyl C-H...O hydrogen bond as a critical factor in enantioselective Lewis-acid catalyzed reactions of aldehydes. Chem. Commun. 2001,1321-1329. 

The development of enantioselective Mannich-type reactions is an important subject in synthetic organic chemistry, because fhese reactions provide optically active nitrogen-containing compounds which are very valuable in syntheses of biologically active products and their derivatives. Until recently, this subject had been solved by use of chiral auxiharies [215]. In recent years, catalytic asymmetric Mannich-type reactions using chiral Lewis acids have been studied extensively [216]. This section deals wifh chiral Lewis acid-promoted reactions. 

The Lewis acid-promoted reaction of aldehydes with a-substituted allylsilanes affords 3-silyltetrahydrofurans, in good to high yields, with homoallyl alcohols [476-479]. The use of homochiral a-substituted allyl- and crotyldimethylphenylsilanes realizes highly diastereo- and enantioselective syntheses of tri- and tetrasubsti-tuted THF derivatives, which can be converted into 3-hydroxy-THF derivatives by oxidative cleavage of the carbon-silicon bond (Scheme 10.171) [476-478]. 

Keywords Diels-Alder reaction. Cycloaddition, Lewis acids, Enantioselective catalysis... 

An early example of Lewis acid-catalyzed reactions conducted under continuous flow was demonstrated by Moberg and co-workers [49] and employed the enantioselective addition oftrimethylsilyl cyanide (TMSCN) (75) to benzaldehyde (21) (Scheme 6.20). 

Most recent research has been focused on the application of polymers as chiral auxiliaries in enantioselective Lewis-acid-catalyzed reactions. Studies of Itsuno and co-workers [44] culminated in the development of a polymer-supported catalyst containing a chiral oxazaborolidinone with oxyethylene crosslinkages which gave the Diels-Alder adduct of cyclopentadiene and methacrolein in 88 % isolated yield with an exotendo ratio of 96 4 and 95 % e. e. for the exo adduct. A variety of polymer-supported chiral Lewis acids was also investigated by Mayoral et al. [45]. Some supported catalysts were more active than their homogeneous analogs, but enantioselectivity was always lower. 

In all of the examples considered so far, the chiral element has been employed in stoichiometric quantities. Ultimately, it would be desirable to require only a small investment from the chirality pool. This is only possible if the chiral species responsible for enantioselectivity is catalytic. It is worth stating explicitly that, in order to achieve asymmetric induction with a chiral catalyst, the catalyzed reaction must proceed faster than the uncatalyzed reaction. One example of an asymmetric aldol addition that has been studied is variations of the Mukaiyama aldol reaction [110] whereby silyl enol ethers react with aldehydes with the aid of a chiral Lewis acid. These reactions proceed via open transition structures such as those shown in Figure... 

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