Enantioselective asymmetric allylboration

The last class of allylation reactions that are amenable to asymmetric catalysis employs allylboronate derivatives. Schaus reported that several chiral BINOL deri vatives catalyze the enantioselective asymmetric allylboration of acyl imines [97]. This reaction is most effective when 3,3 diphenyl BINOL acts as the catalyst and allyldii sopropoxyborane is the nucleophile. The allylation products are obtained in good yields (75 94%) and excellent enantiomeric excesses (>90% ee) for both aromatic and aliphatic imines (Table 1.13). 

Z)-l-Methyl-2-butenylboronate 7 undergoes an exceptionally enantioselective reaction with benzaldehyde (99% ee), propanal (79%. 98% ee), 2-methyl-2-propenal (85%, 99% ee), and ( )-2-methyl-2-pentenal (81 %, 99% ee)10 38. Excellent enantioselectivity is also realized in reactions of the analogous chiral a-methyl-) y-disubstituted allylboronate27 40. Whether the l,2-dicyclohexyl-l,2-ethanediol auxiliary plays a beneficial role in this reaction, as suggested above for the asymmetric allylboration reactions of 6, has not yet been determined. 

We began these studies with the intention of applying this tandem asymmetric epoxidation/asymmetric allylboration sequence towards the synthesis of D-olivose derivative 63 (refer to Figure 18). As the foregoing discussion indicates, our research has moved somewhat away from this goal and we have not yet had the opportunity to undertake this synthesis. This, as well as the synthesis of the olivomycin CDE trisaccharide, remain as problems for future exploration. Because it is the enantioselectivity of the tartrate ester allylboronates that has limited the success of the mismatched double asymmetric reactions discussed here, as well as in several other cases published from our laboratorythe focus of our work on chiral allyiboronate chemistry has shifted away from synthetic applications and towards the development of a more highly enantioselective chiral auxiliary. One such auxiliary has been developed, as described below. 

Homochiral borolanes 99-102 can asymmetrically allylborate aldehydes164. The better enantioselectivity exhibited by borolane 102 than others is due to the steric origin offered by the Me3Si group. 

Chiral addition of allyl metals to imines is one of the useful approaches toward the synthesis of homoallylic amines. These amines can be readily converted to a variety of biologically important molecules such as a-, / -, and y-amino acids. Itsuno and co-workers utilized the allylborane 174 derived from diisopropyl tartrate and cr-pinene for the enantioselective allylboration of imines. The corresponding iV-aluminoimines 173 are readily available from the nitriles via partial reduction using diisobutylaluminium hydride (DIBAL-H) <1999JOM103>. Recently, iV-benzyl-imines 176 have also been utilized for the asymmetric allylboration with allylpinacol boronate 177 in the presence of chiral phosphines as the chiral auxiliaries to obtain homoallylic A -benzylamines 178 in high yield and selectivity (Scheme 29) <2006JA7687>. 

Although Brown and co-workers proposed a six-membered transition state for the asymmetric allylboration reaction in which the aldedyde oxygen initially coordinates to boron followed by an internal transfer of the allyl group from boron to the carbonyl carbon,8 a quantitative analysis to explain the enantioselectivity was not available until 1993, when Gennari et al. conducted a computational study to rationalize the enantiofacial selectivity of Brown allylation9 (Scheme 3.1g). Calculation predicts that transition state A, in which the allyl group attacks the si-lace of the aldehyde, is favored over transition state B by 2.12kcal/mol. 

The asymmetric allylboration of achiral aldehydes with a substituted chiral al-lylborolane 193 and ( )- or (Z)-194 has been reported [128]. The enantioselectiv-ity observed with (5)-193 at -100 C and aldehydes is uniformly high with all of the achiral aldehydes examined (Scheme 10-75). The enantioselection observed with the borolane 193 is proposed to be primarily steric in origin and not from any stereoelectronic component. The reaction likely proceeds via a closed, six-membered transition structure in which the aldehyde is coordinated such that the trimethylsilyl group is oriented anti to the developing B-0 bond. 

Generally the reaction of unsaturated aldehydes (aromatic, olefmic and acetylenic) with chiral boronates has provided homoallylic alcohols in low to moderate enantioselectivity [124]. However, the enantioselectivity of the allyl- and 2-bu-tenylborations of benzaldehyde and unsaturated aldehydes is significantly improved when a metal carbonyl complex is utilized as the substrate [131]. For example, the reaction of iron carbonyl-complexed diene 225, chromium carbonyl-complexed benzaldehyde 226 and dicobalt hexacarbonyl-complexed acetylene 227 all give significantly increa.sed allyl and 2-butenylboration selectivities compared to the parent aldehydes (Fig. 10-6). In the case of chiral substrates 225 and 226, these species can be obtained in enantioenriched form by kinetic resolution by use of the asymmetric allylboration reaction. 

Scheme 3.12 illustrates the polymer-supported aUylboron reagents derived from chiral N-sulfonylamino alcohols and used for the asymmetric synthesis of homoal-lylic alcohols and amines (see Scheme 3.12) ]29]. All of these asymmetric allylbora-tions were performed using the polymeric chiral aUylboron reagent prepared from triallylborane and PS-supported N-sulfonylamino alcohols 38-41. High levels of enantioselectivity were obtained in the asymmetric allylboration of imines with the polymeric reagent derived from norephedrine.

The enantioselective asymmetric allylation of imines has been a synthetic challenge, the initial solutions of which required stoichiometric amounts of chiral allylbor on [87], allylsilane [88], allylzinc [89], or allylindium reagents [90]. Itsuno showed that a chiral B allyloxazaborolidine derived from norephedrine could add to the N trimethylsilyl imine prepared from benzaldehyde in high yield and enantiomeric excess (Scheme 1.22) [91]. Brown later reported that B allyldiisopinocamphenylbor ane is also very effective for the allylation of the same electrophiles, but the addition of a molar amount of water is necessary to obtain high yields [92]. The diastereo and... 

Originally, enantiosdective allylboration was developed using chiral allylbo-ranes and allyl boronates. These reactions require multistep preparahons of chiral reagents that are used in stoichiometric amoimts, and are therefore impractical. Recently, catalytic asymmetric allylborations were developed. These reactions can apply either chiral Lewis bases or BBonsted acids as the catalysts, hi particular, chiral BlNOL-phosphoric acids were demonstrated to provide high optical yields in the enantioselective allylboration reaction between allylboronate 1 and aldehydes. For example, the catalytic asymmetric allylboration of benzaldehyde 2 proceeded quantitatively yielding the corresponding homoallyl alcohol 3 with 98% ee ( heme 3.1). 

Scheme 3.47 Asymmetric allylborations of 3-decynal dicobalt hexacarbonyl cobalt-induced reversal of enantioselectivity.

The SPINOL-based phosphoric acid (157) has been found to be a general, highly enantioselective catalyst for asymmetric allylboration of aldehydes with pinacol allylboronates (156). Excellent enantioselectivities have been obtained for different types of aldehydes including aromatic... 

Chiral, nonracemic allylboron reagents 1-7 with stereocenters at Cl of the allyl or 2-butenyl unit have been described. Although these optically active a-substituted allylboron reagents are generally less convenient to synthesize than those with conventional auxiliaries (Section 1.3.3.3.3.1.4.), this disadvantage is compensated for by the fact that their reactions with aldehydes often occur with almost 100% asymmetric induction. Thus, the enantiomeric purity as well as the ease of preparation of these chiral a-substituted allylboron reagents are important variables that determine their utility in enantioselective allylboration reactions with achiral aldehydes, and in double asymmetric reactions with chiral aldehydes (Section 1.3.3.3.3.2.4.). 

The increased enantioselectivity of 88 is also apparent in reactions with chiral aldehydes (Figure 28). p-Alkoxypropionaldehydes 90 were relatively poor substrates when 36 was used.3 The best selectivity ever obtained for syn diastereomer 91 in the matched double asymmetric reactions was 89 11 [(S,S)-36 and 90a], whereas the best selectivity for anti diastereomer 92 was 87 13 [reaction of 90b and (R,R)-36. In contrast, the allylborations of 90a,b with the new reagent 88 now proceed with up to 97 3 selectivity for either product diastereomer. Even more impressive results were obtained with glyceraldehyde acetonide (23) the matched double asymmetric reaction leading to 29 now proceeds with 300 1 diastereoselectivity, while the mismatched combination leading to 30 proceeds with 50 1 selectivity. 

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