A-substituted allylboronates

Several applications of this methodology to the synthesis of racemic a-substituted allylboronates are provided in refs 2-4. It is noted that reagents 6 (X = Br) and 7 are unstable with respect to ailyl rearrangement of the halide ions, either thermally or in tile presence of halide ion, and so care must be exercised in the preparation and handling of a-haloallvlboronates. 

Conceptually related methods have been employed in the synthesis of a-substituted allylboron reagents 85 and 106. In the case of 8, a benzimidazoleoxy leaving group is introduced as part of the a-alkoxy-2-butenyllithium reagent. Fragmentation of the ate complex must be conducted at — 100 °C in order to avoid the isomerization of 8, which occurs readily if 8 is allowed to warm to — 78 °C for one hour before addition of an aldehyde5. 

An extremely attractive feature of the route outlined at the beginning of this section for the transformation of boronates 3 or 4 to a-substituted allylboron compounds 5 is that reagents with very high enantiomeric purity (> 90% ee) may be prepared when precursors such as 3 and 4, and therefore also ate complex 1, contain a suitable diol chiral auxiliary17. The following syntheses of (S)-68, lib9, and 1310 illustrate this feature. 

A second route to a-substituted allylboronates involves the functionalization of substituted allylorganometallic precursors with a suitable borylating agent. Several examples of this method are summarized below. 

These reagents are not isolated but are used directly in reactions with aldehydes, after generation of ate complexes via the addition of an alkyllithium reagent or pyridine11. 2-(2-Propenyl)-1,3,2-dioxaborolane is also metalated upon treatment with lithium tetramethylpiperidide, but mixtures of a- and y-substitution products are obtained upon treatment of this anion with alkylating agents20. Consequently, this route to a-substituted allylboron compounds appears to be rather limited in scope. 

Single Asymmetric Induction Reactions of Chiral a-Substituted Allylboron... 

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.). 

Double asymmetric reactions of chiral a-substituted allylboron reagents 1-5 and chiral aldehydes are summarized in this section. 

With the analogous reagent 125, however, the corresponding allylboronate intermediate 126 is thought to favor a transition structure 127 where the a-substituent is positioned in a pseudo-axial orientation in order to escape nonbonding interactions with the bulky tetraphenyl dioxaborolane (Eq. 99). This way, a Z-configured allylic alcohol unit of opposite configuration is obtained in diol product 128. This type of steric control with chiral a-substituted allylboronates... 

Carosi, L. Lachance, H. Hall, D. G. Additions of Functionalized A-Substituted Allylboronates to Aldehydes under the Novel Lewis and Bronsted Acid Catalyzed Manifolds. Tetrahedron 2005, 46, 8981-8985. 

Copper(II)-catalyzed Boryl Addition to Allylic Carbonates. The conversion of allylic carbonates to chiral a-substituted allylboronates was also investigated by Hoveyda, who was able to accon ilish this transformation with a Cu(II)-NHC complex. This reaction proceeds in a vinylogous fashion to Sawamura s, but under these conditions, (E)- and (Z)-allylic carbonates undergo substitution to produce opposite enantiomers of product with similar yields and selectivity. This methodology is also tolerant of substitution at the a- or -position and is effective for di-or trisubstituted alkyl (linear or branched) or aryl alkenes delivering a quaternary a-chiral allylboronate product with up to 98% enantioselectivity (eq 49). 

The minimization of gauche pentane interactions in the transition stales is also an important consideration in the reactions of substituted allylboronates and a-heteroatom-substituted aldehydes4,52d 54,56. Transition states 8 and 11 have been identified by Roush and Hoffmann as the least sterically hindered ones accessible in reactions with (E)- and (Z)-allylboronates. 

Several studies of reactions of configurationally unstable a-substituted allylboranes have also been reported19,29. The reactions of dialkyl[( )-l-alkyl-2-butenyl]boranes and aldehydes at — 78 °C provide a mixture of syn- and an/i -diastereomers. reflecting reactions by both the Z-and /f-isomers. When generated and used at — I00°C, however, the ff/m-diastereomer is obtained with >95% diastercoselectivity and >90% selectivity for the /T-olefin isomer by way of a transition state analogous to 429. This result suggests that the allylboron isomerization is slow at —100 JC relative to carbonyl addition. 

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). 

Roush, W R, Adam, M A, Walts, A E, Harris, D J, Stereochemistry of the reactions of substituted allylboronates with chiral aldehydes. Factors influencing aldehyde diastereofacial selectivity, J. Am. Chem. Soc., 108, 3422-3434, 1986. 

In situ generation of CH2 CHCH(Li)Cl and its trapping with triisopropyl borate provides new access to 1-chloroallylboronate [33] which is a valuable intermediate for the synthesis of variously substituted allylboronates via the reaction with organolithi-ums (eq (21)). 

The a-halomethylboronate alkylation method (Scheme 13) is extremely useful for the preparation of substituted allylboronates that cannot be prepared via the allyl anion route. Notable examples that fall into this category are (80)-(82). ° - The only limitation to this method as a preparative route is the occasional coproduction of alkenylboronates that presumably arise via an a-elimination pathway involving the ate complex generated upon addition of (64) to (65). ... 

Results of representative reactions of substituted allylboronates and achiral aldehydes are summarized in Table 1. It is noteworthy that in the majority of cases the reaction diastereoselectivity closely parallels the isomeric purity of the reagents, thus underscoring the requirement that the allylboronate syndesis be highly stereoselective. Dimethyl crotylboronates (68) and (69) are more reactive than (1) and (2), as indicated by the fact that the reactions of (68) and (69) are complete within a few hours at -78 °C while those of (1) and (2) include an overnight period at room temperature. Reagents (73)-(79) are even less reactive than (1) and (2), their reactions requiring several days at room temperature to reach completion. A detailed study of the temperature dependence of diastereoselectivity, however, has not been reported to date. 

The stereochemistry of the reactions of oxime ethers and crotylboronates (22) and (23) have been discussed earlier (Scheme 8). The reactions of the corresponding oximes with (22) and (23) appear to follow a similar stereochemical course (Scheme 14). Stereoselectivity, however, is not as high with the isobutyraldehyde and pentanal oximes as it is with phenylaldoxime. The reaction of MeaSi-substituted allylboronate (90) and acetaldehyde oxime performed in refluxing CCU similarly provides a 79 21 mixture of the anti and syn product diastereomers (MeaSi replacing Me in 25 and 26). Excellent stereoselectivity for syn-homoallylamines has been achieved via the Lewis acid catalyzed reactions of aldimines and crotyltributylstannane. ... 

The use of optically pure a-chloroalkyl boronic esters as electrophiles, e.g. the dicyclohexyl boronate 18 obtained from Matteson s elegant methodology [41], lends access to a-alkyl substituted allylboronates (e.g., 19) with very high diastereomeric purity by way of a net inversion of configuration (Equation 9) [42]. Likewise, alkenylmetal fragments react with chiral dichloromethylboronate 20 to afford optically pure a-chloroallylboronates such as 21 (Equation 10) [43]. Subsequent addition of these a-substituted reagents to aldehydes is highly stereoselective. Furthermore, the chloride... 

Intramolecular versions of the above allylic substitutions have been developed. For example, Hoffmann and Dresely reported in 1986 that treatment of the optically active y-siloxyalkenylboronate 47 provides the useful a-chloro-( )-crotylboronate 48 with an almost perfect level of chirality transfer (Equation 27) [71]. Schlapbach and Hoffmann more recently reported the preparation of a-sulfonamido allylboronates by sequential treatment of 47 with SOCI2 and the corresponding lithiated sulfon-... 

In contrast to the preparative methods described above, a functionalized allyl-boronate can be created from a simpler allylboronate by olefin cross-metathesis [81, 82]. Here, treatment of pinacol allylboronate (2) with various olefin partners, exemplified with styrene in Equation (33), in the presence of ruthenium catalyst 58 smoothly furnishes a more elaborate 3-substituted allylboronate, the cross product 38 [81]. These reactions are noteworthy for their exceptional functional group tolerance allylboronates bearing primary halides can be directly synthesized using this method. Unfortunately, the E/Z selectivity in the formation of the 3-substituted allylboronates is variable. This metathesis approach to allylboronates was employed as the beginning of a tandem cross-metathesis/carbonyl allylation process [82] (discussed in more detail in Section 6.4.1.3). 

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