Asymmetric aldol reactions using chiral

An extensive study on Sn(OTf)2-catalyzed asymmetric aldol reactions " using chiral diamine ligands derived from proline has been carried out. Of particular significance is that the enantioselectivity can be switched completely by slight changes of the ligand structures. 

Asymmetric Aldol Reactions Using Chiral Boron Enolates... 

Yamashita Y, Ishitani H, Shimizu H, Kobayashi S. Highly anti-selective asymmetric aldol reactions using chiral zirconium catalysts. Improvement of activities, structure of the novel zirconium complexes, and effect of a small amount of water for the preparation of the catalysts. J. Am. Chem. Soc. 2002 124 3292-3302. 

Sn(OTf)2 can function as a catalyst for aldol reactions, allylations, and cyanations asymmetric versions of these reactions have also been reported. Diastereoselective and enantioselective aldol reactions of aldehydes with silyl enol ethers using Sn(OTf)2 and a chiral amine have been reported (Scheme SO) 338 33 5 A proposed active complex is shown in the scheme. Catalytic asymmetric aldol reactions using Sn(OTf)2, a chiral diamine, and tin(II) oxide have been developed.340 Tin(II) oxide is assumed to prevent achiral reaction pathway by weakening the Lewis acidity of Me3SiOTf, which is formed during the reaction. 

Based on this assumption, the asymmetric aldol reaction of chiral 1,3-oxazolidines 1 of methyl ketones was examined. It was found that the corresponding aldol products were obtained in good optical purity when divalent tin chloride was used as an additive metal salt. 

Corey and colleagues applied their catalyst to the asymmetric Henry (nitro aldol) reaction using chiral aminoaldehydes and the short-step synthesis of an HIV protease inhibitor (Scheme 3.9) [26]. Interestingly, a newly generated asymmetric center is controlled by the chiral catalyst and nitrogen substituents. 

Kiyooka S-i (1997) Development of a chiral lewis acid-promoted asymmetric aldol reaction using oxaborolidinone. Rev Heteroatom Chem 17 245-270... 

Catalytic versions of the asymmetric aldol reaction using simple lithium enolates and substoichiometric amounts of a chiral catalyst are rare611. The bimetallic system proposed by Shibasaki and coworkers deserve to be mentioned at this point. The combination of a... 

Early investigations of asymmetric aldol reactions with chiral carbohydrate auxliliaries were carried out by Heathcock [152] and Bandraege [159], but often only low stereoselectivities were observed. In additional studies. Banks et al. [73] used oxazinone auxiliaries for aldol reactions, which had been employed for other asymmetric reactions. The lithium enolate of the A-acylated oxazinone 226 reacted with benzaldehyde, furnishing exclusively the iyn-aldols 227A and 227B in a ratio of 10 1 (Scheme 10.76). 

In the previous synthesis, two asymmetric aldol reactions using dienyl silyl ethers were described, one using a chiral Lewis acid for stereoinduction while the other used substrate control from a chiral aldehyde. This can be compared with the use of chiral dienolate 131 in the synthesis of a Ci-Cie fragment of the bryo-statins (Scheme 9-41) [59J. Here, the menthyl-derived auxiliary is covalently attached to the enolate, and again an excellent level of asymmetric induction was achieved on addition to aldehyde 132 to give adduct 133. 

Evans et al. utilized the chiral oxazolidones to prepare optically pure 3-hydroxy-a-amino acids, - important constituents of peptides and 3-lactams. As shown in Scheme 31, an asymmetric aldol reaction using the boron enolate derived from the V-(a-haloacyl)oxazolidone (68) provides the jyn-3-hydroxy-ot-halocarbonyl derivative (69), which is converted to the ann-3-hydroxy-a-azidocarbonyl derivative (70)... 

These findings brought about extensive studies of asymmetric aldol reactions using silyl enol ethers of thiol esters that employed other chiral diamines [24] or organometals such as Cu [25], Zr [26], Ti [27], B [28], Sc [29], and Pr... 

In the total synthesis, the most noteworthy aspect is the philosophy of the approach. Also, the important point is not just the total yield, but, primarily the completion of the synthesis, as artists never exhibit their unfinished work and since a synthesis cannot be an Unfinished Symphony. Considering the many kinds of useful reactions which have been developed to serve as synthetic key steps, such as asymmetric epoxidation, asymmetric reduction and enantiospeci-fic aldol reaction using chiral reagents, and, considering the many kinds of enantiomerically pure materials such as carbohydrates which are available, any complex antibiotic may be synthesized. Consequently, a philosophy of synthesis is more urgently required than ever before. 

Scheme 23 Asymmetric aldol reactions using Pr(OTf)3 and chiral bis-pyridino-18-crown-6...

The aldol reaction is another class of reactions used to highlight AE, as all the atoms in the reactants end up in the product. One should note though that this transformation comes with a number of caveats. Typically, a stoichiometric base is required to form the reactive enolate, and for many asymmetric aldols, a chiral auxiliary is utilized. Although this auxiliary is present in the product after the reaction, it is usually cleaved in a subsequent step and discarded to waste. An example of innovation to address both of these issues is the asymmetric aldol reaction using a zinc-Pro-Phenol... 

ASYMMETRIC ALDOL REACTIONS USING THE OXAZOLIDONE CHIRAL AUXILIARY... 

Nerz-Stormes M, Thornton ER. Asymmetric aldol reactions. Use of the titanium enolate of a chiral N-acyloxazolidinone to reverse diastereofacial selectivities. J. Org. Chem. 1991 56 (7) 2489-2498. 

Diastereoselective Aldol Reactions Using Chiral Enolates Although the approach that uses chiral auxiliaries or other elements of stoichiometric chiral information is not as elegant as asymmetric catalysis, it is highly practical. At present, the boron-mediated aldol reaction of enolates 112 and 115 with aldehydes giving the syn aldol products 113 and 116 constimtes one of the best C C bond forming methods (Scheme 10.26). ... 

Furuta K, Maruyama T, Yamamoto H. Catalytic asymmetric aldol reactions. Use of a chiral (acyloxy)borane complex as a versatile Lewis-acid catalyst. J. Am. Chem. Soc. 1991 113 1041-1042. 

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