Boron Allylation Reaction

The enantioselectivity calculated from this energy difference agrees well with the experimental value. 

Reaction of 4-(pivaloyloxy)benzaldehyde with the E -crotyldiisopinocampheylbo-rane d19E gave the corresponding homoallylic alcohol 22 in a 98 2 enantiomeric ratio. After protection of the alcohol as a tert-butyldiphenylsilyl (TBDPS) ether, the alkene was subjected to ozonolysis to provide the 3-hydroxy aldehyde 23. 

In an effort to elucidate the electronic effects in the stereochemistrydetermining transition states, Gung and co-workers conducted a computational study in 2002.21 The calculations carried out on the allylation reaction between 

The tartrate-based E-crotylboronate (S,S)-43E, which can readily be prepared 

CH2CI2 or toluene at -78 C produced the corresponding homoallylic alcohol 84 in excellent optical purities and greater than 90% yield. 

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To explain the stereochemical outcome of the reaction of allylic boron reagents with carbonyl compounds, Houk and Li carried out calculations on the transition structures of the model reaction of formaldehyde and allylboronic acid6 (Scheme 3.V). The bimolecular complex formed initially between allylboronic acid and formaldehyde would rearrange via a six-membered transition state to form an intermediate. Calculations show that chair transition state A is 8.2kcal/ mol more stable than twist-boat transition structure B, clearly confirming that the six-membered chairlike transition-state model is a legitimate scheme to predict the stereochemical outcome of the boron allylation reaction. 

For a comprehensive review of synthetic applications of asymmetric boron allylation reactions, see Chemler, S. R. Roush, W. R. in Modem Carbonyl Chemistry Otera, J., Ed. Wiley-VCH Weinheim, Germany, 2000 Chapt. 11. 

The synthesis in Scheme 13.37 also used a me,ro-3,4-dimethylglutaric acid as the starting material. Both the resolved aldehyde employed in Scheme 13.36 and a resolved half-amide were successfully used as intermediates. The configuration at C(2) and C(3) was controlled by addition of a butenylborane to an aldehyde (see Section 9.1.5). The boronate was used in enantiomerically pure form so that stereoselectivity was enhanced by double stereodifferentiation. The allylic additions carried out by the butenylboronates do not appear to have been quite as highly stereoselective as the aldol condensations used in Scheme 13.37, since a minor diastereoisomer was formed in the boronate addition reactions. 

Si. rra(pentafluorophenyl)boron was found to be an efficient, air-stable, and water-tolerant Lewis-acid catalyst for the allylation reaction of allylsilanes with aldehydes.167 Sc(OTf)3-catalyzed allylations of hydrates of a-keto aldehydes, glyoxylates and activated aromatic aldehydes with allyltrimethylsilane in H2O-CH3CN were examined. a-Keto and a-ester homoallylic alcohols and aromatic homoallylic alcohols were obtained in good to excellent yields.168 Allylation reactions of carbonyl compounds such as aldehydes and reactive ketones using allyltrimethoxysilane in aqueous media proceeded smoothly in the presence of 5 mol% of a CdF2-terpyridine complex (Eq. 8.71).169... 

By using allylation reaction of aldehydes with chiral allylic boronate A in Scheme 52, Lebreton synthesized (R)-35 and (S)-34 via ( )-B and (S)-C, respectively [78]. 

Garcia et al.75 have introduced another boron reagent 114 that can also be used in asymmetric allylation reactions. 

Although the allylation reaction is formally analogous to the addition of allylboranes to carbonyl derivatives, it does not appear to occur through a cyclic transition state. This is because, in contrast to the boron in allyl boranes, the silicon in allylic silanes has no Lewis acid character and would not be expected to coordinate at the carbonyl oxygen. The stereochemistry of addition of allylic silanes to carbonyl compounds is consistent with an acyclic transition state. Both the E- and Z-stereoisomers of 2-butenyl(trimethyl)silane give the product in which the newly formed hydroxyl group is syn to the methyl substituent.64 The preferred orientation of approach by the silane minimizes interaction between the aldehyde substituent R and the methyl group. 

The palladium-catalyzed reaction of diboron with allyl acetates or chlorides is a convenient alternative to transmetallation method for the synthesis of functionalized boronates. The reaction of diboron 119 with allyl acetates309-312 smoothly occurred without the assistance of a base, whereas the presence of AcOK was critical for the coupling with allyl chlorides313 (Equation (57)). The boron atom coupled with the less-hindered terminal carbon giving the thermally stable (if)-allyl boronates. Thus, the (E)- and (Z)-cinnamyl acetate, chloride (entries 1-4), and their secondary derivatives (entries 7 and 8), all afforded an (if)-cinnamyl boronate. The borylation of prenyl acetate was slow (entry 6), but the corresponding chloride (entry 5) and tertiary derivative (entry 9) worked well for the same purpose (Equation (58)).309,310... 

The coupling occurred at the less-hindered terminal carbon giving thermally stable ( )-allyl boronates. Thus, the (.E)- and (Z)-crotyl chloride, and 3-chloro-l-butene, all afforded an (A)-crotyl boronate. The reaction with benzyl halides gave benzyl boronates.333... 

Unusual and otherwise difficult to obtain boronates can be made by addition of a xanthate to allyl or vinyl boronates. The reaction proceeds in the same way as for ordinary olefins and compounds containing a boronate... 

Carbonyl Allylation and Propargylation. Boron complex (8), derived from the bis(tosylamide) compound (3), transmeta-lates allylstannanes to form allylboranes (eq 12). The allylboranes can be combined without isolation with aldehydes at —78°C to afford homoallylic alcohols with high enantioselectivity (eq 13). On the basis of a single reported example, reagent control might be expected to overcome substrate control in additions to aldehydes containing an adjacent asymmetric center. The sulfonamide can be recovered by precipitation with diethyl ether during aqueous workup. Ease of preparation and recovery of the chiral controller makes this method one of the more useful available for allylation reactions. 

In their synthesis of olivin, the aglycon segment of olivomycin A, Roush and coworkers used a highly diastereoselective substrate-directed y-alkoxy allylation reaction to set the C(l ) stereocenter [80]. Thus, reaction of the aldehyde 90, derived from L-threonine, with the [(Z)-y-methoxyallyl]boronate 91 resulted in the highly diastereoselective formation of adduct 92. The stereochemistry of 92 is consistent... 

In recent years, catalytic asymmetric Mukaiyama aldol reactions have emerged as one of the most important C—C bond-forming reactions [35]. Among the various types of chiral Lewis acid catalysts used for the Mukaiyama aldol reactions, chirally modified boron derived from N-sulfonyl-fS)-tryptophan was effective for the reaction between aldehyde and silyl enol ether [36, 37]. By using polymer-supported N-sulfonyl-fS)-tryptophan synthesized by polymerization of the chiral monomer, the polymeric version of Yamamoto s oxazaborohdinone catalyst was prepared by treatment with 3,5-bis(trifluoromethyl)phenyl boron dichloride ]38]. The polymeric chiral Lewis acid catalyst 55 worked well in the asymmetric aldol reaction of benzaldehyde with silyl enol ether derived from acetophenone to give [i-hydroxyketone with up to 95% ee, as shown in Scheme 3.16. In addition to the Mukaiyama aldol reaction, a Mannich-type reaction and an allylation reaction of imine 58 were also asymmetrically catalyzed by the same polymeric catalyst ]38]. 

As shown in Scheme 3, classic approaches to p-hydroxy ketones are often ineffective for the formation of hydroxypropionates. Standard aldol reactions are complicated by the presence of the P-alkoxide of 4. Enolization of 4 typically results in facile P-elimination, thus preventing aldol addition and formation of hydroxypropionate 7. This approach was later successfully applied to the myriaporone problem by Loh through the use of boron enolates. Likewise, relatively few allylation reactions are appropriate for hydroxypropionate synthesis as the required organometallic species 8 would also be prone to elimination. 

Fandrick et al. used the same strategy to form a catalyst in situ for the preparation of zinc ethoxide from diethyl zinc and ethanol, to catalyze allylation of a wide range of ketones by allyl pinacol boronate, 122 (reaction 7.26) with over 90% yield [76]. 

Conditions A temperature/time (°C/h) for the boronation reaction. Conditions B temperature/time (°C/h) for the allylation reaction. 

Kennedy JWJ, Hall DG (2003) Recent advances in the activation of boron and silicon reagents for stereocontroUed allylation reactions. Angew Chem Int Ed 42 4732-4739... 

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). 

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