Lewis acid catalysis 1,3-dipolar

The regioselectivity benefits from the increased polarisation of the alkene moiety, reflected in the increased difference in the orbital coefficients on carbon 1 and 2. The increase in endo-exo selectivity is a result of an increased secondary orbital interaction that can be attributed to the increased orbital coefficient on the carbonyl carbon ". Also increased dipolar interactions, as a result of an increased polarisation, will contribute. Interestingly, Yamamoto has demonstrated that by usirg a very bulky catalyst the endo-pathway can be blocked and an excess of exo product can be obtained The increased di as tereo facial selectivity has been attributed to a more compact transition state for the catalysed reaction as a result of more efficient primary and secondary orbital interactions as well as conformational changes in the complexed dienophile" . Calculations show that, with the polarisation of the dienophile, the extent of asynchronicity in the activated complex increases . Some authors even report a zwitteriorric character of the activated complex of the Lewis-acid catalysed reaction " . Currently, Lewis-acid catalysis of Diels-Alder reactions is everyday practice in synthetic organic chemistry. 

The author has been involved for quite a long time in the study of Lewis acid catalysis of 1,3-dipolar cycloaddition reactions. From his research group, a series of methodologies directed to the Lewis acid-mediated stereochemical and regiochem-ical control of 1,3-dipolar cycloaddition reactions has been reported this includes ... 

The reactions of diazoalkanes and imines occur in generally low yields, but Lewis acid catalysis is of some help (equation 40). The reaction involves a 1,3-dipolar mechanism which proceeds through an isolable triazoline intermediate (Scheme 21). Treatment of the latter with acid affords aziridine in modest yield. 

An enantioselective 1,3-dipolar cycloaddition of nitrones 187 with ethyl vinyl ether 194 catalyzed by Brpnsted acid catalyst 195 was reported by Yamamoto and co-workers. Scheme 3.63 [80]. Only 5 mol% of this air-stable catalyst was used, and the reactions were completed within 1 h. The endo-selectivity of this cycloaddition is different to the previously reported cjto-selectivity of the aluminum-catalyzed reaction (Lewis acid catalysis). 

Jiao, P., Nakashima, D., Yamamoto, H. (2008). Enantioselective 1,3-dipolar cycloaddition of nitrones with ethyl vinyl ether The difference between Brpnsted and Lewis acid catalysis. Angewandte Chemie International Edition, 47, 2411-2413. 

In the same year, a successful Lewis acid catalysis was developed by Sedelmeier et alP The group synthesized 5-substimted tetrazoles in a direct conversion using dial-kylaluminium azides (57), which are inexpensive, soluble in organic solvents and nontoxic (Scheme 9.9). The proposed mechanism for the 1,3-dipolar cycloaddition (Scheme 9.9A) suggests Lewis acid properties of the aluminium center activating the nitriles in the azide addition. Different 5-substituted tetrazoles (63) were obtained in excellent yields after a simple workup procedure (Scheme 9.9B). However, the reaction tanperature varied between -40 °C and 120 °C, depending on the reactivity of the substrates. 

The first effective enantioselective 1,3-dipolar cycloaddition of diazoalkanes catalyzed by chiral Lewis acids was reported in the year 20(X) (139). Under catalysis using zinc or magnesium complexes and the chiral ligand (R,/ )-DBFOX/Ph, the reaction of diazo(trimethylsilyl)methane with 3-alkenoyl-2-oxazolidin-2-one 75 (R = H) gave the desilylated A -pyrazolines (4S,5R)-76 (R =Me 87% yield, 99% ee at 40 °C) (Scheme 8.18). Simple replacement of the oxazohdinone with the 4,4-dimethyloxazolidinone ring resulted in the formation of (4R,5S)-77 (R = Me 75% yield, 97% ee at -78 °C). 

Nitrones are the most widely studied of the 1,3-dipoles in the field of catalyzed enantioselective 1,3-dipolar cycloaddition reactions. Effective catalysis using a variety of chiral Lewis acid catalysts has been reported for the nitrone cycloaddition... 

Abstract This review is devoted to the stereoselectivity of intermolecular (intramolecular cycloadditions are not included) 1,3-dipolar cycloadditions of sugar-derived nitrones. Stereoselective cycloaddition (transformation of isoxazolidine followed by reduction of the N O bond to produce both an amino and a hydroxy function) allows the synthesis of tailor-made products of possible biological interest such as pol>4iydroxylated pyrrolidines, pyrrolizidines, indolizidines, fi-aminocarbonyl compounds, and disaccharides. Attention is focused on the preparation of isoxazolidinyl nucleosides and to the catalysis of the cycloaddition by Lewis acids. This review has concentrated on the new developments achieved from 1999 to February 2007. 

The effect of the addition of Lewis acid upon the stereoselectivity of cycloaddition of chiral nitrones 3a and 34 to electron-rich alkene, with ethyl vinyl ether and the further transformation of so-prepared isoxazoli-dine 36b to new fi-amino acid ester 40, has been also investigated by the same team (Fig. 10). The 1,3-dipolar cycloaddition of nitrone 3a with ethyl vinyl ether imder AlMes and Et2AlCl catalysis proceeded diastereoselectively and finished at - 8 °C over 20 h, providing only two diastereoisomers 35a and 36a in a ratio of 90 10 with erythro-cis 35a predominant, although four diastereoisomers are possible. Indeed, cycloaddition in the absence of any Lewis acids proceeded very slowly with excess of ethyl vinyl ether at room temperature over 14 days to give a mixture of all four diastereoisomers 35-38 with a considerable decrease of the stereoselectivity in a ratio of 59 12 14 15, although erythro-cis 35a was still the major adduct. The 1,3-... 

It has been found that the rate of reaction between 1-bromohexane and solid potassium chloride is very sensitive to the solvent used [49]. In particular, the rate of reaction was found to depend upon the Lewis basicity and the polarisability of the solvent, but no correlation to the relative permittivity of the solvent was seen. The authors propose that the increase in reaction rate with increased Lewis acidity indicates either a solvent-induced increase in nucleophilicity of the chloride anion, or a contribution by the solvent to the breaking of the carbon—bromine bond. Not surprisingly, the best solvents were found to be dipolar aprotics such as pyridine, hexamethylphosphorus triamide and A,A-dimethylformamide, in which these reactions will proceed without catalysis. 

Copper(I) catalysis has demonstrated its long-held reputation in asymmetric synthesis over the past decade. The moderate Lewis acidity and coordination property of Cu(l) salts make it a versatile metal center in various metal-ligand complex systems and thereby have broad applications in the area of organic chemistry, especially in the asymmetric catalysis field. This chapter summarizes the recent developments of Cu(l)-catalyzed asymmetric cycloaddition and cascade addition-cyclization reactions since 2010. A wide range of asymmetric transformations catalyzed by chiral Cu(l) complexes are discussed, such as the 1,3-dipolar cycloadditions, including [3+2], [3+3], and [3+6] cycloadditions. Other cycloadditions and cascade addition-cyclization reactions are also discussed. 

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