Boron Lewis Acid Catalyzed Enantioselective Diels-Alder Reaction

The complexes are isolated, characterized and used as chiral Lewis acids. Dissociation of the labile ligand liberates a single coordination site at the metal center. These Lewis acids catalyze enantioselective Diels-Alder reactions. For instance, reaction of methacrolein with cyclopentadiene in the presence of the cationic iron complex (L = acrolein) occurs with exo selectivity and an enantiomeric excess of the same order of magnitude as those obtained with the successful boron and copper catalysts (eq 3). ... 

Recently, catalytic asymmetric Diels-Alder reactions have been investigated. Yamamoto reported a Bronsted-acid-assistcd chiral (BLA) Lewis acid, prepared from (R)-3-(2-hydroxy-3-phcnylphenyl)-2,2 -dihydroxy-1,1 -binaphthyl and 3,5A(trifluoromethy I) - be nzeneboronic acid, that is effective in catalyzing the enantioselective Diels-Alder reaction between a,(3-enals and various dienes.62 The interesting aspect is the role of water, THF, and MS 4A in the preparation of the catalyst (Eq. 12.19). To prevent the trimerization of the boronic acid during the preparation of the catalyst, the chiral triol and the boronic acid were mixed under aqueous conditions and then dried. Using the catalyst prepared in this manner, a 99% ee was obtained in the Diels-Alder reaction... 

Enantioselective Diels-Alder reactions of acrolein are also catalyzed by 3-(2-hydroxy-3-phenyl) derivatives of BINOL in the presence of an aromatic boronic acid. The optimum boronic acid is 3,5-di(trifluoromethyl)benzeneboronic acid, with which >95% e.e. can be achieved. The transition state is believed to involve Lewis acid complexation of the boronic acid at the carbonyl oxygen and hydrogen bonding with the hydroxyl substituent. In this transition state, re,re-interactions between the dienophile and the hydroxybiphenyl substituted can also help to align the dienophile.65... 

Chiral boron(III) Lewis acid catalysts have also been used for enantioselective cycloaddition reactions of carbonyl compounds [17]. The chiral acyloxylborane catalysts 9a-9d, which are also efficient catalysts for asymmetric Diels-Alder reactions [17, 18], can also catalyze highly enantioselective cycloaddition reactions of aldehydes with activated dienes. The arylboron catalysts 9b-9c which are air- and moisture-stable have been shown by Yamamoto et al. to induce excellent chiral induction in the cycloaddition reaction between, e.g., benzaldehyde and Danishefsky s dienes such as 2b with up to 95% yield and 97% ee of the cycloaddition product CIS-3b (Scheme 4.9) [17]. 

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. 

Asymmetric Diels-Alder Reaction of Unsaturated Aldehydes . The boron atom of acyloxyborane is activated by the electron-withdrawing acyloxy groups, and consequently acyloxyborane derivatives are sufficiently Lewis acidic to catalyze certain reactions. Thus, asymmetric Diels-Alder reactions of a,p-enals with dienes using (1) as a Lewis acid catalyst have been developed. For example, the reaction of cyclopentadiene and methacrolein gives the adduct in 85% yield (endo exo= 11 89) and 96% ee (major exo isomer) (eq 3). Some additional examples are listed in Figure 1. The a-substituent on the dienophile increases the enantioselectivity, while p-substitution dramatically decreases the selectivity. In the case of a substrate having substituents in both a- and p-positions, high enantioselectivity is observed thus the a-substituent effect overcomes that of the p-substituent. 

The boron-substituent-dependent enantioselectivity of CAB-catalyzed Diels-Alder reactions has been studied as a first step toward obtaining mechanistic information on the sp -sp conformational preferences in a, d-enals, where the possibility of s-cis or s-trans conformers exists in the transition-state assembly of Diels-Alder reaction catalyzed by Lewis acid [12]. a-Substituted a,P-ena s (e.g. methacrolein) favors an s-trans conformation in the transition-state assembly irrespective of the steric features of the boron substituent. On the other hand, the sp -sp conformational preference of a-unsubstituted a,/3-enals (acrolein and crotonaldehyde) can be reversed by altering the structure of the boron substituent an s-trans conformation is preferred when the substituent on the boron is small (H, C=CBu), whereas an s-cis conformation is preferred when the substituent is bulky (o-PhOC(jH4). 

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