Asymmetric allylboration reaction

The cyclohexyloxy(dimethyl)silyl unit in 8 serves as a hydroxy surrogate and is converted into an alcohol via the Tamao oxidation after the allylboration reaction. The allylsilane products of asymmetric allylboration reactions of the dimethylphenylsilyl reagent 7 are readily converted into optically active 2-butene-l, 4-diols via epoxidation with dimethyl dioxirane followed by acid-catalyzed Peterson elimination of the intermediate epoxysilane. Although several chiral (Z)-y-alkoxyallylboron reagents were described in Section 1.3.3.3.3.1.4., relatively few applications in double asymmetric reactions with chiral aldehydes have been reported. One notable example involves the matched double asymmetric reaction of the diisopinocampheyl [(Z)-methoxy-2-propenyl]boron reagent with a chiral x/ -dialkoxyaldehyde87. 

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. 

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. 

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. 

J3,4-trans are 7.0, 3.5, and 2.8 Hz, respectively. These data match well those calculated (7.0, 3.2, and 2.8 Hz) and experimentally determined (6.5, 3.6, 2.8 Hz) for analog 4 53 4. .a 5. Importantly, strong NOE enhancements between HC(4) and HC(3 ) were also observed. A 4.7% enhaneement of HC(3 ) was observed when the HC(4) was irradiated, whereas a 7.4% enhaneement of HC(4) was observed. These results strongly support the conclusion that HC(4) and the alkenyl iodide residue exist in a cis relationship and therefore further confirm the expectation that the R-configuration was obtained in the asymmetric allylboration reaction. 

From (+)-limonene, a hydroboration product, limonylborane (32). was obtained and used in asymmetric allylboration reactions, but with less success than the pinene-derived reagents34 (Section D.2.5.2.). 

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.). 

Hanessian reported the synthesis of enantiomerically pure or highly enriched allylglycine and its chain-substituted analogs from the reaction of the sultam derivatives of O-benzyl glyoxylic acid oxime with ally he bromides in the presence of zinc powder in aqueous ammonium chloride (Eq. 11.41).72 Brown noticed the critical importance of water in the asymmetric allylboration of /V-trimethylsilyIbcnzaldimines with B-allyldiisopinocampheylborane.73 The reaction required one equivalent of water to proceed (Eq. 11.42). 

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. 

A more detailed study has been made by Brown et al. [14]. They found the critical importance of water in the asymmetric allylboration of N-trimethyl-silylaldimines, and concluded that the reaction takes place during the aqueous workup. The allylboration of 19 with 20 proceeded only in the presence of one molar equivalent of water to give 22 in 92% ee and 90% yield (Scheme 8). They suggested that the reactive aldimines could be generated in situ from N-trimethylsilylimines upon addition of one equivalent of water and captured by the allylborating agent. 

Asymmetric allylboration, characteristics, 9, 197 Asymmetric allylic alkylation, allylic alcohols with copper, 11, 99 with iridium, 11, 105 with molybdenum, 11, 109 with nickel, 11, 102 with non-palladium catalysts, 11, 98 with platinum, 11, 103 reaction systems, 11, 112 with rhodium, 11, 104 with ruthenium, 11, 108 with tungsten, 11, 111... 

In the total synthesis of (+)-trienomycins A and F, Smith et al. used an Evans aldol reaction technology to construct a 1,3-diol functional group8 (Scheme 2.1i). Asymmetric aldol reaction of the boron enolate of 14 with methacrolein afforded exclusively the desired xyn-diastereomer (17) in high yield. Silylation, hydrolysis using the lithium hydroperoxide protocol, preparation of Weinreb amide mediated by carbonyldiimidazole (CDI), and DIBAL-H reduction cleanly gave the aldehyde 18. Allylboration via the Brown protocol9 (see Chapter 3) then yielded a 12.5 1 mixture of diastereomers, which was purified to provide the alcohol desired (19) in 88% yield. Desilylation and acetonide formation furnished the diene 20, which contained a C9-C14 subunit of the TBS ether of (+)-trienomycinol. 

The asymmetric allylboration of representative aldehydes with either 9R or 9S was examined in EE (3h, -78 °C). In all cases, the homoallylic alcohols 10 were obtained in i96% ee. These results are summarized in Table 2. The intermediates 11 were isolated in excellent yields in essentially pure form after solvent removal. For the reactions of 9R, solutions (-0.5 M) of SR and (IS, 25)- (+)- pseudoephedrine (1.0 equiv) in MeCN were heated at reflux temperature to effect the transesterification with crystalline (+)-8 being isolable by simple filtration. An analogous procedure was used for the 95 reactions employing (-)-pseudoephedrine to... 

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. 

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). 

Only Nicolaou s synthesis [143a,c] is described in this section (Scheme 82), because the results of olefin metathesis at the Cl2 and C13 positions, the key reaction of this strategy, are almost the same. The Cl-Cl 2 acid 573 was synthesized as the coupling partner. The Brown asymmetric allylboration of p-keto aldehyde 569 followed by TBS protection furnished 570, which was oxidized... 

Hoffmann has continued his pioneering work in asymmetric allylboration and synthesized several heterocyclic compounds (26). Soderquist has developed a new reagent, chiral 5-allyl-10-trimethylsilyl-9-borabicyclo[3.3.2]-decane for allylboration reactions (27). 

Scheme 5 Asymmetric induction in intramolecular allylboration reactions...

Recently we undertook the preparation of chiral lactones of different ring sizes utilizing chiral homoallylic alchols derived from the asymmetric allylboration of appropriate aldehydes as the starting materials (6-S). Our procedures are reviewed here. The application of our allylboration-esterification-ring closing metathesis reaction sequence for the synthesis of biologically active natural products (S-/i) are also summarized. 

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). 

From Aminoadds. - (+)-Galactostatin 54 has been synthesized by one- then two-carbon chain extensions of the D-serine derivative 53, using different thiazole reagents (Scheme 13) see Scheme 16 for an alternative synthesis of galactostatin. The calicheamycin constituent sugar 56 was obtained by asymmetric allylboration of the L-serinal derivative 55 (Scheme 14), as part of a comprehensive study of similar reactions. ... 

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. 

---