Chiral Boron Lewis Acids

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]. 

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... 

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... 

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... 

In sharp contrast to the utility of chiral boron Lewis acids, chiral aluminum Lewis acids have been little used for asymmetric aldol reactions of silyl enolates since the first example reported by Reetz et al. [115]. Fujisawa et al. have reported that an equimolar amount of a chiral Lewis acid prepared from Et2AlCl and a bor-nane-2,3-diol promotes the aldol reaction of 48 in moderate yields with good enantioselectivity [127]. 

Consult ref. [14]. For this synthetic protocol, an enantioselective version has been elaborated [15] using chiral boron Lewis acids. 

In the enantioselective synthesis of natural dolabellane [30], the chiral boron Lewis acid 15 was used to generate the enolate of the macrocychc lactone 16. The boron enolate rearranged smoothly to give the cycloundecidienoic acid 17. This acid was further converted to natural dolabellane (Scheme 5.1.19). 

This chapter will focus on the developments in the applications of boron Lewis acids from 1998 to 2006 and at the same time highlight key benchmarks prior to 1998. Both achiral and chiral boron Lewis acids are discussed in each section. 

In the previous edition of this book, many excellent examples of chiral boron Lewis acid catalysts were highlighted. These chiral Lewis acids have stood the test of time in terms of efficiency. Early examples of catalytic enantioselective Diels-Alder reactions employ chiral dibromo-boron type catalyst (1), where Kaufmann and coworkers have observed moderate selectivity in the reaction of methyl acrylate with cyclopentadiene (Equation 1) [1]. 

Enantioselective examples involving chiral boron Lewis acids were well covered in the previous issue of this monograph however, examples (75)-(80) are mentioned... 

AntiUa and Wulff used axially chiral boron Lewis acids containing 3,3 -diphenyl-2,2 -bi-l-naphthalol (VANOL) and 2,2 -diphenyl-(4-biphenanthrol) (VAPOL) for asymmetric alkylative cyclization between ethyl diazoacetate and A7-benzhydrylimines 169 to obtain aziridine 170 with high yield, excellent cis trans ratio, and enantiomeric excess (Scheme 40.33). ... 

Yamamoto developed a conceptually new class of chiral boron-Lewis acids 174 (Equation 20) that can readily be assembled from a tetraphenol ligand and B(OMe)3 [93, 94]. These were shown to be especially effective with a wide range of a-substituted enals in enantioselective Diels-Alder reactions. One illustrative example is the cycloaddition between aldehyde 173 and cyclopentadiene to give 175 in 99% ee, > 99 1 exo/endo selectivity, and quantitative yield [93]. Yamamoto suggested that these catalysts 174 were Bransted-assisted chiral Lewis acids (termed BLAs), in which the phenol proton activates the enal substrates by hydrogen bonding, as depicted in the proposed transition state assembly 176. 

---