Boronic ester, diastereoselective

Diastereoselective homologation of chiral alkylboronates (cf. 12, 80-81). Investigations of this reaction have been carried out mainly on boronic esters (1)... 

In three separate papers, the use of chiral boronic esters in 1,3-dipolar cycloadditions with nitrile oxides have been described (316-318). The reaction of 203 with nitrile oxides proceeded with low diastereoselectivities (Scheme 12.58). 

Results obtained in the conversion of boronic esters of C2 symmetry 1 or 2 to a-chloro boronic esters 4 and on to secondary alkyl boronic esters 6 are summarized in Table 1. For example, the data with R2 = isopropyl, utilized material of only 97% ce38 and significantly underestimated the diastereoselectivity. 

Tablet. Diastereoselection in the Synthesis of Secondary Alkyl Boronic Esters. 

The catalyzed hydrogenation of alkenylboronic esters was used for the diastereoselective synthesis of alkylboronic esters 276446 (Equation (75)). The hydrogenation of a pyrrolboronic acid provided a prolineboronic acid, which was then resolved by HPLC to give an optically active boronic ester 277447 (Equation (76)). 

Boronic ester homologation. (R,R)-2,3-Butanediol- and (-(- )-pinanediol have been used as the chiral adjuncts in a diastereoselective homologation of dichloromethaneboronic esters (1) to the (aS)-a-chloroboronic esters (2). Reaction of 1 with an alkyllithium produces a borate complex (a), which rearranges diastereoselectively in the presence of ZnCl, to 2 with introduction of a chiral center adjacent to boron. The reaction permits... 

Diastereoselective allylation of optically pure sulfinyl dienal complexes using tributyl allyltin can be obtained (Scheme 138). 2,4-Hexadien-1,6-dial iron tricarbonyl complex (88) undergoes nucleophilic addition reactions with diaUcylzincs in the presence of a catalytic amount of an optically active amino alcohol (Scheme 139). Very high enantio-and diastereoselectivity is observed. Related reactions of (88) with chiral allyl boronic esters give allylated alcohols in very high enantiomeric excess. 

The transfer of the allylic moieties from boron to the electrophilic carbonyl carbon proceeds via rearrangement to form intermediate boronic esters C and D (see below). The reaction is highly diastereoselective. The ( )-crotylboronate reacts to give the anfr-homoallylic alcohol and the (Z)-crotylboronate reacts to afford the syn-homoallylic alcohol.This behavior has been interpreted in terms of the Zimmerman-Traxler chair-type transition state model.Because of the double bond geometry, coordination of the (Ei-crotylboronic ester places the Me preferentially equatorial, whereas coordination of the (Z)-crotylboronic ester places the Me axial, as illustrated in the cyclohexane chair-form transition state conformations A and B, respectively. In both cases, the R moiety of the aldehyde must occupy a pseudo-equatorial position to avoid steric repulsion by one of the OR substituents on boron. 

Sterically demanding boronic esters can be used to achieve diastereoselective trifluoromethylation of steroid substructures (Scheme 2.160). Chiral boronates act as effective auxiliaries for the enantioselective trifluoromethylation. 

Therefore, for the construction of boron-based pentam-eric macrocycles 9a-f, they performed a condensation of aryl- and alkylboronic acids with 3,4-dihydroxypyridine 8 in which 5 boronate esters are connected by dative B—N bonds (Scheme 4.6) [11]. This procedure was inspired in then-previous work [12]. The boron atoms of these complex structures represent chiral centers, and the assembly process is highly diastereoselective. 

In earlier work, we had shown that lithium enolates of esters react with a-bromo boronic esters in a highly diastereoselective manner (25). A similarly high level of diastereocontrol prevails in the cyclization of cyano substituted boronic esters (24). We chose to concentrate first on closure of cyclobutanes. 

The first synthesis of an (a-haloalkyl)boronic ester [8], a free radical addition of a tetrahalomethane, was followed by mechanistic studies that indicated the potential for stereospecific alkylation with Grignard reagents via borate intermediates [9], if only there had been a way to obtain asymmetric examples. The discovery of the efficient reaction of (dichloromethyl)lithium with boronic esters to form (a-chloroalkyl)boron-ic esters by insertion of a CHCl group into the B-C bond opened a new opportunity [10]. Boronic esters of pinanediol, prepared from (+)-a-pinene by osmium tetroxide catalyzed oxidation, were soon found to undergo the insertion reaction with a strong asymmetric bias, with diastereomeric selectivities frequently in the 90-95% range [llj. It was subsequently found that anhydrous zinc chloride promotes the reaction and increases diastereoselectivity to as high as 99.5% in some cases [12]. 

Scheme. 20 Diastereoselective reaction of (a-haloalkyl)boronic esters with an ester enolate.

In a related papCT, high diastereoselectivity with secondary amines was cOTifmned, while the use of chiral primary amines generally gives products with low to moderate diastereoselectivity [17], Factors affecting the efficiency and stereoselectivity of this reaction, in particular of the structure of the boronate ester and amine, were also determined. 

Boronic esters (3) can be homologated to a-chloroboronic esters (4) (Scheme 2) replacement of the chlorine atom by carbon nucleophiles, such as Grignard reagents, and oxidation of the carbon-boron bond gives a new route to alcohols/ If the sequence is performed with (+)- or (-)-pinanediol boronic esters it can be made into a directed chiral synthesis of alcohols, as illustrated in Scheme 3 from phenyl boronic acid the homologation steps were found to occur with diastereoselectivities in excess of 90%, the chlorine replacement proceeds with inversion, and the oxidative step with retention of configuration. 

Thus, the pinane diol derivative 78 was reacted with dimethyl-4-bromobutylboronate 79 to afford the boronic ester 80 in good yield. A one-carbon homologation was then achieved by first treating the boronic ester 80 with lithium methylene dichloride, which affords an intermediate boronate 81, that undergoes a diastereoselective rearrangement to afford the a-chloroboronic ester 82. 

Pietruszka has reported the synthesis of stable enantiomerically pure functionalized cyclopropyl boronic esters via highly diastereoselective cyclopropanation of the respective alkenyl boronic esters with diazomethane catalyzed by Pd(OAc)2(119]. The enantiomerically pure alkenyl boronic esters were prepared by direct hydroboration of the respective alkynes with the chiral 1,3,2-dioxaboro-lane (144). The ter-butyldimethylsilyl protecting group in the boronic ester could be selectively deprotected and the resulting hydroxymethyl alkenyl boronate was also cyclopropanated to give hydroxymethylcyclopropyl boronic esters with good diastereoselectivity (Scheme 3.78). 

---