Boronic Lewis acidity

Scheeren et al. reported the first enantioselective metal-catalyzed 1,3-dipolar cycloaddition reaction of nitrones with alkenes in 1994 [26]. Their approach involved C,N-diphenylnitrone la and ketene acetals 2, in the presence of the amino acid-derived oxazaborolidinones 3 as the catalyst (Scheme 6.8). This type of boron catalyst has been used successfully for asymmetric Diels-Alder reactions [27, 28]. In this reaction the nitrone is activated, according to the inverse electron-demand, for a 1,3-dipolar cycloaddition with the electron-rich alkene. The reaction is thus controlled by the LUMO inone-HOMOaikene interaction. They found that coordination of the nitrone to the boron Lewis acid strongly accelerated the 1,3-dipolar cycloaddition reaction with ketene acetals. The reactions of la with 2a,b, catalyzed by 20 mol% of oxazaborolidinones such as 3a,b were carried out at -78 °C. In some reactions fair enantioselectivities were induced by the catalysts, thus, 4a was obtained with an optical purity of 74% ee, however, in a low yield. The reaction involving 2b gave the C-3, C-4-cis isomer 4b as the only diastereomer of the product with 62% ee. 

The most successful approach in this reaction category has been the use of chiral boron Lewis acid catalysts, in the addition of ethyl diazoacetate to imines reported by Wulff (Scheme 1.33) [59-60]. 

Probably the most widely applicable asymmetric imine aziridination reaction reported to date is that of Wulff et al. These workers approached the reaction from a different perspective, utilizing the so-called vaulted , axially chiral boron Lewis acids VANOL and VAPOL [35] to mediate reactions between ethyl diazoacetate and N-benzhydrylimines (Scheme 4.29) [36]. The reactions proceed with impressive enantiocontrol, but there is a requirement that the benzhydryl substituent be present since this group is not an aziridine activator there is, therefore, a need for deprotection and attachment of a suitable activating group. Nonetheless, this method is a powerful one, with great potential for synthesis, as shown by the rapid synthesis of chloroamphenicol by the methodology [37]. 

Boron-based Lewis acids are often used in organic syntheses. Since the boron atom has an empty / -orbital, many boron compounds can function as Lewis acids. Typical boron Lewis acids are boron trihalides, for which Lewis acidity increases according to the order of fluoride < chloride < bromide < iodide, the reason for this order being the relative abilities of the different halogens to act as 7r-donors to boron. 

Chiral boron Lewis-acid complexes have been successfully used in Diels-Alder and aldol reactions. Representative chiral Lewis-acidic boron compounds are shown in Figure 2.297-301... 

Since dienolates 1 and 2 represent diacetate synthons, the dienolate derived from 6-ethyl-2,2-dimethyldioxinone can be seen as a propionate-acetate syn-thon. The synthesis of the corresponding dienolate provides a mixture of the E and Z enolates in a 3 5 ratio. The reaction with Ti-BINOL complex 5 generates a 5 1 mixture with the syn isomer as the major diastereomer. After separation of the diastereomers, the enantiomeric excess of the syn isomer was determined to be 100%. The anti isomer was formed in 26% ee. The same transformation performed with boron Lewis acid 7 gave the anti isomer as the major compound, but only with 63% ee. The minor syn isomer was produced with 80% ee. The observed selectivity could be rationalized by an open transition state in which minimization of steric hindrance favors transition state C (Fig. 1). In all three... 

Trifluoromethylation of Enolate Anions with a Suitable Combination of Boron Lewis Acids (94JOC5692)... 

Alkyl-substituted pyridines have been complexed with a wide variety of other boron Lewis acids, BH3, B(OH)3, and BX3, where X is a selection of alkyl, aryl, hydroxy, alkoxy, and aryloxy groups <87JCS(P2)77l). 

In the original paper, Renaud and co-workers hypothesized that complex 45, resulting from the complexation of methoxycatecholborane, generated in situ from the excess of catecholborane and methanol, was the main source of H atoms. The authors proposed that the O-H bond of methanol was activated by complexation with the boron Lewis acid (Scheme 39). 

A calix[4]arene bearing one chiral boron Lewis acid at the wide rim was used with modest success as a catalyst in a Diels-Alder reaction.20... 

Trifluoromethylation of enolates could be achieved by complexing the enolate with boron Lewis acids (Equation 118). The best boron Lewis acid for this purpose was 2-phenyl-l,3,2-benzodioxaborole 231. For enantio-selective trifluoromethylation, the optically active boron compound 232 was used (Equation 119). 

Other Uses. Reagent 1 has been used for enantioselec-tive enolborination, albeit with poor (1.1 1) selectivity. Similar bis-sulfonamide-derived boron Lewis acids have been used for aldol additions, "" ester-Mannich reactions, Diels-Alder reactions, Ireland-Claisen reactions, and [2,3]-Wittig rearrangements. Similar bis-sulfonamide-derived aluminum Lewis acids have been used for aldol additions, Ehels-Alder... 

Fu et al. have developed a boron Lewis acid that bears both an empty a-symmetry orbital and an empty jr-symmetry orbital (Fig. 1) [162]. These vacant orbitals can simultaneously accept electron density from an oxygen lone pair and from the tt system of a carbonyl group. For instance, an X-ray diffraction study of air- and moisture-sensitive [( -borabenzene-THF)Cr(CO)3] reveals the THF binds to the boron atom... 

This chapter addresses chirally modified boron Lewis acid complexes, in which there has been increased interest because of their capacity to induce chirality. They have been successfully used for Diels-Alder, aldol, and a variety of other miscellaneous reactions. I will describe and analyze here the different types of catalyst and classify them according to their efficiency, selectivity, and flexibility. 

The first asymmetric Simmons-Smith reaction with a chiral Lewis acid catalyst was introduced in 1994 by Charette and Juteau and featured a chiral boron Lewis acid prepared from tartaric acid [32]. Although this process resulted in excellent enantioselec-tivity, it would not turnover, i.e. the yield was less than 10 %. In the same year Imai, Takahashi and Kobayashi introduced a chiral aluminum Lewis acid that would catalyze the cyclopropanation of allylic aleohols with significant turnover numbers but their system did not lead to asymmetric induction as high as that resulting from the dioxaborolane catalyst [33]. The catalyst is prepared from the bis-sulfonamide 132... 

The Diels-Alder reaction is a key reaction in organic synthesis. Its high versatility in the synthesis of six-membered ring compounds and its potential for the control of up to four stereogenic centers have attracted much attention. Lewis acid catalysis has further enhanced the scope of this reaction. Lewis acids activate the dienophile by coordination to a Lewis basic substituent (usually a carbonyl group) and direct the stereochemistry. Boron Lewis acids are often the catalysts of choice for the Diels-Alder reaction. Early (Ti(IV)) and late (Cu(II)) transition metal complexes in combination with chiral ligands have also been used with much success and the reader is referred to the relevant chapters in this book. 

It is a generally accepted tenet that the Lewis basicity of trivalent group 15 compounds decreases with the heavier congeners. As the triorgano substituted complexes are generally easier to investigate than the hydrides, numerous studies have been concerned with the Lewis base interaction of R3E compounds (E = P, As, Sb, Bi) with boron Lewis acids and with the proton affinity (PA) of R3E and EH3 species The proton affinities of a series of PhjE compounds (E = P, As, Sb) have been determined... 

Although crystal structures of other bimolecular complexes of carbonyls with boronic Lewis acids have not been reported, a number of intramolecular chelates have been detected in the solid state. In all these cases boron is found to lie in the direction of the carbonyl lone pair with no more than 11 distortion away from the best plane of the carbonyl group. The average B—O bond length is 1.581 0.019 A and the B—O—C angle lies between 112 and 119. ... 

Masamune et al. examined the catalytic activity of several boron Lewis acids derived from BH3 THF and the p-toluenesulfonamides of simple a-amino acids towards the aldol reaction of benzaldehyde with TMS enolate 48 [121]. As a result, the borane catalysts derived from a,a-disubstituted glycine p-tolueriesulforiarriides were found to have high activity. The disubstitution would accelerate the second step (Step II) of the catalytic cycle (Scheme 10.43). On the basis of this observation, they developed chiral borane catalysts 47 c and 47 d, which enable highly enantioselective aldol reactions of KSA and thioketene silyl acetals (84—99% ee with 48). 

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