Boronic oxazaborolidine derivatives

A major advance in the evolution of chiral boron reagents was reported initially by Itsuno and co-workers in 1981.5 Stereoselectivities up to 73% ee were observed using the 1,3,2-oxazaborolidine derived from p-amino alcohols. Thus (S)-valinol 5 in reaction with borane afforded 6. 

Boronic acids and their derivatives are very popular as components of chiral Lewis acids and promoters for various reaction processes [481]. Indeed, the chiral acyloxyb-oranes and the oxazaborolidines (Section 1.2.3.5) described in Chapter 11 made a mark in organic synthesis. Recently, Ryu and Corey extended the apphcation of chiral oxaborolidinium catalysts to the cyanosilylation of aldehydes [482]. Chiral diaz-aborohdine salts were evaluated in the enantioselective protonation of enol ethers [145]. Likewise, a tartramide-derived dioxaborolane is key as a chiral promoter in the asymmetric cyclopropanation of allyhc alcohols [483]. More examples and details on the applications of boronic add derivatives as reaction promoters and catalysts are provided in Chapter 10. 

A series of chiral boron catalysts prepared from, e.g., N-sulfonyl a-amino acids has also been developed and used in a variety of cycloaddition reactions [18]. Corey et al. have applied the chiral (S)-tryptophan-derived oxazaborolidine-boron catalyst 11 and used it for the conversion of, e.g., benzaldehyde la to the cycloaddition product 3a by reaction with Danishefsky s diene 2a [18h]. This reaction la affords mainly the Mukaiyama aldol product 10, which, after isolation, was converted to 3a by treatment with TFA (Scheme 4.11). It was observed that no cycloaddition product was produced in the initial step, providing evidence for the two-step process. 

An expedient and stereoselective synthesis of bicyclic ketone 30 exemplifies the utility and elegance of Corey s new catalytic system (see Scheme 8). Reaction of the (R)-tryptophan-derived oxazaboro-lidine 42 (5 mol %), 5-(benzyloxymethyl)-l,3-cyclopentadiene 26, and 2-bromoacrolein (43) at -78 °C in methylene chloride gives, after eight hours, diastereomeric adducts 44 in a yield of 83 % (95 5 exo.endo diastereoselectivity 96 4 enantioselectivity for the exo isomer). After reaction, the /V-tosyltryptophan can be recovered for reuse. The basic premise is that oxazaborolidine 42 induces the Diels-Alder reaction between intermediates 26 and 43 to proceed through a transition state geometry that maximizes attractive donor-acceptor interactions. Coordination of the dienophile at the face of boron that is cis to the 3-indolylmethyl substituent is thus favored.19d f Treatment of the 95 5 mixture of exo/endo diastereo-mers with 5 mol % aqueous AgNC>3 selectively converts the minor, but more reactive, endo aldehyde diastereomer into water-soluble... 

The oxazaborolidines are easily prepared by heating ephedrine with borane dimethyl sulfide or the appropriate boronate ester. The aluminum reagent C is obtained by mixing ephedrine and trimethylaluminum. Borolidinc A is superior to its methyl derivative B and to the aluminum analog C. The diastereomeric borolidine obtained from borane and (S,S)-pseu-doephedrine failed to show any cnantioselectivity25. A variety of aromatic aldehydes can be enantioselectively alkylated in the presence of A, however, with heptanal the enantioselectivity is poor25. 

The characteristic feature of the aforementioned oxazaborolidine catalyst system consists of a-sulfonamide carboxylic acid ligand for boron reagent, where the five-membered ring system seems to be the major structural feature for the active catalyst. Accordingly, tartaric acid-derived chiral (acyloxy)borane (CAB) complexes can also catalyze the asymmetric Diels-Alder reaction of a,P-unsaturated aldehydes with a high level of asymmetric induction [10] (Eq. 8A.4). Similarly, a chiral tartrate-derived dioxaborolidine has been introduced as a catalyst for enantioselective Diels-Alder reaction of 2-bromoacrolein [11] (Eq. 8A.5). 

The structure of enantiopure 1,3,2-oxazaborolidine was first characterized by Corey [22]. The oxazaborolidine is prepared from an amino alcohol and borane or substituted boronic acids (Scheme 1) [23,24,25]. B-Methyl derivatives of oxazaborolidine were prepared by the reaction of an amino alcohol with trimeth-ylboroxine [26,27]. 

This reduction method has a number of advantages that include wide scope, predictable absolute stereochemistry, ready availability of the chiral catalyst in both enantiomeric forms, high yields, experimental ease, recovery of the catalyst (as the amino alcohol), and low cost of goods. The most common form of the chiral oxazaborolidine is derived from prolinol and has a methyl substituent on the boron atom (B-Me-CBS) 1. When one conducts a reduction on a novel system for the first time, this catalyst provides a good compromise of cost, enantioselectivity, and experimental ease. If sufficient control is not observed with this reagent, one can then systematically evaluate the numerous variations of this framework. 

Oxazaborolidines (70) have been used extensively in organic synthesis and their preparation from substituted prolinol derivatives and alkyl boronic acids is well documented (Equation (7)) <88JOC2861, 9lJOC75l>. Earlier workers prepared related compounds starting from bis(dimethylamino) phenylborane <85JOM(294)l> but the boronic acid route has now superseded this. 

Enantiomerically pure boron-based Lewis acids have also been used successfully in catalytic aldol reactions. Corey s catalyst (7.10a) provides good enantioselectivity with ketone-derived silyl enol ethers, including compound (7.11). Other oxazaborolidine complexes (7.13) derived from a,a-disubstituted a-amino acids give particularly high enantioselectivity, especially with the disubstituted ketene... 

Among nonmetal chiral complexes, chiral oxazaborolidines have been found effective in many D-A reactions. The adduct obtained from the D-A reactions of 5-benzyloxymethyl-l,3-cyclopentadiene 98a with a-bromoacrolein in the presence of catalyst 98 (S-tryptophan-derived oxazaboroUdine) is an important intermediate in the synthesis of prostaglandins. The aldehyde group of the dienophile is bound to the catalyst by coordination with boron by Lewis interaction and the Lewis complex is stabilized by H-bonding. The upper face of the aldehyde is shielded by indole moiety of the catalyst. The benzyloxymethyl substituent of the cyclopentadiene produces a steric differentiation on the two faces of cyclopentadiene ring resulting the approach of the diene preferably from one face. 

Very recently, Corey and coworkers have introduced the very powerful cationic chiral Lewis acids (14) [15] and (15) [16], which are derived from protonation of the parent oxazaborolidines with triflic acid and triflimide, respectively. Because of this protonation, the boron atom becomes even more acidic. The authors have demonstrated that catalyst (14) is able to efficiently promote the cycloadditions of 2-substituted acroleins with a variety of dienes (Equation 5) [15]. 

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