Allylic pinacols

Allylic pinacols. Reduction of ketones bearing an electron-withdrawing group with TiCli in the presence of a,p-enals results in coupling to allylic pinacols in 45 85% yield. Example ... 

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]. 

The TiCl3-H20-promoted cross-coupling reaction has been extended to the addition of a carbonyl compound to a,P-unsaturated aldehydes [80c]. The addition occurs selectively to the carbon atom of the carbonyl group, and highly functionalized allylic pinacols are obtained with good yields. 

The lactone A was also used as starting material in the synthesis of the primary prostaglandins via an allylic substitution-semi-pinacolic rearrangement sequence (Ref. 2). 

Allylboronates prepared from simple diols display appreciable reactivity, but eyelie boronate derivatives prepared from 1,2- or 1,3-diols display considerably less. The commonly employed pinacol esters are among the least reactive members of this class. 2-Allyl-3-methyl-l,3,2-oxaza-... 

Similar stereoselectivities are achieved in the allylation of enantiomerically pure proline-derived a-oxoamides47. l-Bromo-3-methy]-2-butcne reacts with clean allylic inversion. Since pinacol-type coupling products are also produced under the reaction conditions, this was taken as evidence for a radical addition mechanism47. 

Mn. Manganese is also effective for mediating aqueous carbonyl ally-lations and pinacol-coupling reactions. Manganese offers a higher reactivity and complete chemoselectivity toward allylation of aromatic aldehydes.178... 

A recently reported vinylation of nitrones was accomplished by using ZnMe2 and vinylboronic esters of pinacol 256. The optimal conditions for the addition were 3.5 h at 60 °C in DMF. Yields of the products, A -allylic hydro-xyamines 257, varied significantly from 14% to 92% (Scheme 137).359... 

Durandetti et al. have described iron-catalyzed electrochemical allylation of carbonyl compounds with allylic acetates (Equation (27)).333 In the case of aldehydes, slow addition of the corresponding aldehyde is required in order to avoid pinacol formation. With crotyl acetate (R3 = Me), the reaction proved to be highly regioselective, providing almost exclusively branched homoallylic alcohols 150. 

The cocatalytic effects of pinacol in the phase transfer catalysis (PTC) of dihalocarbene additions to alkenes were noted by Dehmlow and co-workers who showed that pinacol accelerates the PTC deprotonation of substrates up to pKa 27.7 Dehmlow also studied the effects of various crown ethers as phase transfer catalysts in the addition of dibromocarbene to allylic bromides.8 In Dehmlow s study, elevated temperature (40°C) and dibenzo-18-crown-6 did not give the highest ratio of addition/substitution to allyl bromide. However, the submitters use of pinacol,... 

As a conseqnence of their superior stability, many types of allylic boronates can be isolated and purified. It should be noted that most pinacol allylic boronic esters and other bnlky esters are stable to hydrolysis and can be conveniently pnrified by chromatography on silica gel. A potential pitfall of all allylic boron componnds is their stereochemical integrity, and snbstituted allylic boranes are known to nndergo reversible borotropic rearrangements at temperatures above —45° (see Eq. 12, M = Eor this reason, allylic boranes are nor-... 

Recently, the first examples of catalytic enantioselective preparations of chiral a-substituted allylic boronates have appeared. Cyclic dihydropyranylboronate 76 (Fig. 6) is prepared in very high enantiomeric purity by an inverse electron-demand hetero-Diels-Alder reaction between 3-boronoacrolein pinacolate (87) and ethyl vinyl ether catalyzed by chiral Cr(lll) complex 88 (Eq. 64). The resulting boronate 76 adds stereoselectively to aldehydes to give 2-hydroxyalkyl dihydropyran products 90 in a one-pot process.The diastereoselectiv-ity of the addition is explained by invoking transition structure 89. Key to this process is the fact that the possible self-allylboration between 76 and 87 does not take place at room temperature. Several applications of this three-component reaction to the synthesis of complex natural products have been described (see section on Applications to the Synthesis of Natural Products ). 

The use of chiral Br0nsted acids is illustrated in Eq. 93 as a method for catalyst-controlled double diastereoselective additions of pinacol allylic boronates. Aside from circumventing the need for a chiral boronate, these additions can lead to very good amplification of facial stereoselectivity. For example, compared to both non-catalyzed (room temperature, Eq. 90) and SnCU-catalyzed variants, the use of the matched diol-SnCU enantiomer at a low temperature leads to a significant improvement in the proportion of the desired anti-syn diastereomer in the crotylation of aldehyde 117 with pinacolate reagent (Z)-7 (Eq. 93). Moreover, unlike reagent (Z)-ll (Eq. 91) none of the other diastereomers arising from Z- to E-isomerization is observed. 

As described above in Eq. 43, simple allylboronates can be transformed into more elaborated ones using olefin cross-metathesis. " Treatment of pinacol allylboronate 31 with a variety of olefin partners in the presence of Grubbs second-generation catalyst 142 smoothly leads to formation of 3-substituted allylboronates 143 as cross-metathesis products (Eq. 104). Unfortunately, these new allylic boronates are formed as mixtures of geometrical isomers with modest E/Z selectivity. They are not isolated but rather are treated directly with benzaldehyde to give the corresponding homoallylic alcohol products in good yields (Table A). 

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