Allylboration esters

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. 

N-Methylated y-amino-p-hydroxy acids are accessible by the usual synthetic sequences, i.e. aldol condensation or y-amino-P-oxo ester reduction, starting from the corresponding N-methylated a-amino acids, but are obtained with low diastereoselectivity. 61-63 Alternatively, Brown allylboration of the ALBoc-ALMe amino aldehyde 16 (R1 = Bzl, X=Boc, Y = Me) gives the allyhc N-methylated intermediate 27 in 64% yield and 90% de (Scheme 12). 64 Oxidative cleavage of the alkenol is performed using the two-step ozonolysis and sodium chlorite oxidation sequence. 

The ruthenium-catalyzed olefin cross-metathesis to the preparation of functionalized allyl boronates has resulted in a one-pot three-component coupling procedure for the synthesis of functionalized homoallylic alcohols.617,618 The utility of the protocol was demonstrated in asymmetric allylboration using a tartrate ester (Equation (152)).617... 

Lewis acids and Bu4NI catalyzed allylboration with potassium allyl- and crotyltrifluoroborates (Equation (154)).30,40 620,621 The reaction of pinacol ester derivatives was very slow even at room temperature, but Sc(OTf)3 smoothly catalyzed the addition at — 78 °C with high diastereoselectivity (Equation (155)622 and (156)623,624). A palladium pincer complex catalyzed the addition of trifluoroborate to tosylimines (Equation (157)).625... 

The boronic esters (Chart 9) are easily hydrolyzed to the corresponding homoallylic alcohols using triethanolamine 98). Consequently, the allylboration sequence provides a synthesically useful alternative to the familiar Grignard synthesis of homoallylic alcohols. However, the protonolysis by triethanolamine causes a problem in the isolation of homoallylic alcohol from the thick, sticky, air sensitive boron-containing mixture. Fortunately, treatment of a pentane solution of borinate esters of 9-BBN with 1-equivalent of ethanolamine results in the rapid formation of a fluffy white... 

The intramolecular allylboration of an aldehyde function leads selectively to cir-disubstituted cyclic ethers. It has been shown that both the reactive aldehyde and the allylboronate moiety can be initially generated in situ in a masked form and then liberated simultaneously by hydrolysis of the precursor functions <1997JA7499>. This methodology was successfully applied to the one-pot synthesis of the oxocene 82, a precursor of (-l-)-laurencin (Scheme 13). A DIBAL reduction of the Weinreb amide 80, metalation with r f-butyllithium, borylation with the pinacol borate ester, and, finally, liberation of both the aldehyde and the allylboronate function by aqueous pH 7 buffer solution generated the reactive 81, which cyclized in 38% overall yield to the oxocene 82. Only the all-cis-diastereomer is formed, which means that the cyclization proceeds under high asymmetric induction from the resident stereogenic center present in 80. 

By a similar method, the (Z)-crotylborate is synthesized from cA-2-butene in 70-75% yield with a 98% isomeric purity. The tartrate esters of allylboronic acids are an excellent reagent for asymmetric allylboration of carbonyl compounds. Allyl(diisopinocampheyl)borane [51] and the allylic boron derivatives of ester and amide, such as camphordiol [52], pinanediol [53], 1,2-diphenyl-1,2-ethylenediamine [54], have also been successfully used for asymmetric allylboration of carbonyls. 

Roush and co-workers have shown that the nature of the substituents on the dioxaborolane auxiliary profoundly affects the rate and enantioselectivity of the allylboration reaction reagents with ester substituents are far more reactive and more selective than reagents with alkyl substituents. The enantioselectivity of reagents 1-3 is thought to arise more from electronic attraction and repusion than from steric hindrance. 

The reaction of 54e with acetone proceeds smoothly at -10°C to give borinic ester 55 (Scheme 2.33) [50]. Since the allylboration of carbonyl... 

Certain functionalities like halides can be tolerated allylboration with unhindered aldehydes and ketones are far faster than those with esters and amides. The former groups are readily allylborated in the presence of latter. 

Liberation of the aldehyde from 31 was followed by cyclization to give 32 as a single stereoisomer in up to 60% yield. However, the yields were compromized by partial decomposition of 31 due to the higher acid lability of the y-oxyallylboronate moiety. This induced us to develop an alternate route, in which the allylboronate moiety was generated under in situ protection of the aldehyde function. To this end, the N-methoxy-methyl amide was added to the aldehyde 33 followed by metallation with s-butyllithium. Upon addition of the mixed borate ester the intermediate 34 was formed. Hydrolysis of the reaction mixture with a pH7-buffer solution liberated both the aldehyde and the allylboronate function which immediately underwent the intramolecular allylboration reaction. This resulted in a 74% overall yield of the cyclized product 32. (14)... 

Many other allylborating agents (12-21) utilizing chiral auxiliaries derived from carenes, camphor, tartaric acid, stein, etc. are also known (Figure 2) (2i-33). Recently Villieras described an ester-containing chiral allylborating agent which could be used directly for the synthesis of a-methylene-y-butyrolactones (32). In this review, we have restricted our discussions to the synthesis of lactones via homoallylic alcohols derived from B-allyldiisopinocampheyl-borane, 1. 

Our first synthesis of lactones via allylboration involved the protection of homoallylic alcohols as a p-nitrobenzoate ester, followed by hydroboration with chloroborane and oxidation of the intermediate with CrOa in acetic acid. Deprotection under basic conditions provided the lactones in very high yields with the same enantiomeric excesses as the starting homoallyl alcohols (Scheme 3) (6). 

Asymmetric allylboration of aldehydes containing an adjacent ester group with B-allyldiisopinocampheylborane, followed by hydrolysis and cyclization, provides the corresponding co-allyllactones in high yields and > 92% enantiomeric excess. Hydrogenation of these lactones provides the corresponding w-propyllactones without any loss of optical purity (Scheme 5) (7). 

Our synthesis of ( )-(-)-Argentilactone began with asymmetric allylboration of 2-octynal with (+)-B-allyldiisopinocampheylborane, followed by the stereoselective hydrogenation of the alkynenol in the presence of Lindlar catalyst. This was then converted to the corresponding acrylic ester, and cyclized by refluxing in dichloromethane in the presence of 10 mol% of Grubbs catalyst to provide the natural enantiomer in 44% overall yield (Scheme 8) (9). 

Kennedy and Hall have reported a one-pot allylboration/lactonization using the tetra-substituted 2-alkoxycarbonyl aUylboronates 17 (Section 6.2.1.2) [39]. These allyl-boronates react with aldehydes, thermally and under Lewis acid catalysis, to first provide the hydroxy-ester intermediate 119 (Equation 58). This initial product cyclizes under the reaction conditions by lactonization to afford a-exomethylene y-lactones 120. This facile cyclization is probably a manifestation of the gem-dialkyl effect. In-... 

A new protocol has been introduced to improve selectivity in allylboration of aldehydes. The readily available a-substituted allyl or crotyl pinacol boronic esters often give low A/Z-selectivity. Addition of -butyllithium followed by trapping of alkoxide with TFAA generates an allyl borinic acid, which gives very high -selectivity, and in some cases, this is the opposite of the standard conditions. The borinic ester intermediate was characterized by B-NMR. 

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