Allylboronate, addition

Lewis acid-catalysed allylboronate additions to aldehydes have been reviewed.181... 

We have recently completed the synthesis of 1 with SnMe3 and Sn(Me)Cl2 residues and carried out the X-ray structural analysis of the latter derivative (C. Bolm, Dissertation, Univ. Marburg 1987). We have also completed the synthesis of 3 in optically active form (M.T. Reetz and M. Muller-Gliemann, unpublished results, Univ. Marburg 1988). 3, is useful, inter alia, in enantioselective aldol additions and allylboron additions. 

In a more general view, the most promising choices in this selection of pericyclic carbonyl additions are allylboronates [M = B(OR)2, Section D.1.3.3.3.3.], allyltitanates [M = Ti(OR)3,... 

Chelation control does not operate in the addition of 2-butenyl Grignard reagents to a-oxyalkanals, since with (racemic) 2-benzyloxy-, 2-(benzyloxymethoxy)- and 2-(t< rt-butyldi-methylsilyoxy)propanal similar ratios of isomers are formed28. Several cations were investigated, but the best choices, e.g., allylboronates or allylsilanes, were not included in this study. 

One additional chiral allylboron reagent has been described that is worthy of mention. This is a chiral y-alkoxyallylboronate75. 

For additional examples in which reagent control is exercised in the reactions of chiral allylboron reagents and chiral aldehydes ... 

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. 

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. 

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. 

The addition of allylboronates 1 to the chiral oxime 2 results in the formation of a hydroxyl-amine. This is a general method for the subsequent reductive generation of primary homoallyl-amines, but with poor diastereoselectivity in the case of 3 and 4. A diastereomeric ratio of 90 10 is achieved in the addition reaction, using the chiral allylboronate 59 (double stcrcodifferenti-ation). 

Addition of Allylboronate Ester 176 to Representative Aldehydes (eq. [116]) (132a)... 

The correlation between allylboronic ester stereochemistry and aldehyde diastereoface selection stands in contrast to the behavior of stereochemicaUy defined lithium enolates, which generally exhibit a preference for the Cram mode of addition to chiral aldehydes from either enolate geometry (cf, eqs. [72]-[77]). The stereochemical... 

The synthesis of olivin was recently completed in our laboratories at Indiana University using homoallyl alcohol 15 as a key intermediate. It is beyond the scope of this presentation, however, for us to discuss this synthesis in detail here. For now, therefore, we leave the topic of olivin and consider instead additional applications of allylboronates in the synthesis of carbohydrates and other polyoxygenated materials. 

Moderate levels of diastereomeric differentiation are observed in the additions of achiral allylboronates to P-hydroxy ketones, as exemplified in Eq. 51a. ° The major product is tentatively assigned as the anti diastereomer. Few reports describe the use of carbonyl substrates other than aldehydes and ketones, and these reactions have not led to applications. For instance, low reactivity leading... 

Scheme 4. Stereoinduction model for additions of allylboronate 31 to aldehydes with a polar a-substituent.

Scheme 8. Stereoinduction model for the additions of chiral a-chloro allylboronate 23.

To access anti-l,2-diols, indirect methods are required for the preparation of geometrically pure, chiral E-3-alkoxy reagents. To this end, the isomerization of alkenylboronic esters described above (Eq. 41), provides a reliable route to tartrate-derived E-3-siloxy allylboronate 99 (Fig. 7). The latter shows variable enantioselectivities in additions to aldehydes, with cyclohexanecarboxaldehyde affording the highest selectivity (Eq. 70). ... 

A copper-catalyzed reaction using a chiral diphosphine hgand, DuPHOS, with an added lanthanide salt, provides good levels of enantioselectivity (67-91% ee) in additions of the simple allylboronate 31 to both aromatic and aliphatic ketones that present a large difference of steric bulk on the two sides of the carbonyl group. One such example is shown in Eq. 81. On the basis of B NMR experiments and on the lack of diastereoselectivity in crotylation reactions, the... 

Intramolecular additions generally follow the same trends of stereoselectivity as observed in the bimolecular reactions. Eor example, allylic boronates ( )- and (Z)-118 provide the respective trans- and cis-fused products of intramolecular aUylation. As shown with allylboronate ( )-118, a Yb(OTf)3-catalyzed hydrolysis of the acetal triggers the intramolecular aUylboration and leads to isolation of the trans-fused product 119 in agreement with the usual cyclic transition structure (Eq. 96). 

Allylboronates of type 103 react with equivalent amounts of aldoximes 102 (equation 73) giving allylhydroxylamines 104 in good yields. Similar reactions of aldoximes and glyoxylate oxime ethers with allyl bromide and indium also provide hydroxylamines. Additions of substituted allyl boronates to oximes produce mixtures of stereoisomers with ratio highly dependent on the steric size of substituents in both molecules. Addition of allyltri-n-butyltin to aldoxime ether 105 (equation 74) was found to proceed with a considerable diastereoselectivity. 

Nucleophilic Addition by Allylboron Derivatives. Allylboranes such as 9-allyl-9-BBN react with aldehydes and ketones to give allylic carbinols. Bond formation takes place at the y carbon of the allyl group, and the double bond shifts.33... 

The enantioselective addition of ally organometallics to carbonyls has become one of the workhorses of organic synthesis. Dennis Hall of the University of Alberta reports (J. Am. Chem. Soc. 125 10160, 2003) the scandium triflate catalysis chiral allylboronic acids become more effective tools. The best of these, the Hoffmann camphor derivative 2, adds to aldehydes under Sc(OTf), catalysis with excellent enantiomeric excess. The reaction works equally well for methallyl, and for the E and Z crotyl boronic acids. The crotyl derivatives react with the expected high diastereocontrol. A limitation to the boronate additions is that branched chain aldehydes give low yields. 

Complexes of unsymmetrically substituted conjugated dienes are chiral. Racemic planar chiral complexes are separated into their enantiomers 84 and 85 by chiral HPLC on commercially available /f-cyclodextrin columns and used for enantioseletive synthesis [25]. Kinetic resolution was observed during the reaction of the meso-type complex 86 with the optically pure allylboronate 87 [26], The (2R) isomer reacted much faster with 87 to give the diastereomer 88 with 98% ee. The complex 88 was converted to 89 by the reaction of meldrum acid. Stereoselective Michael addition of vinylmagnesium bromide to 89 from the opposite side of the coordinated Fe afforded 90, which was converted to 91 by acetylation of the 8-OH group and displacement with EtjAl. Finally, asymmetric synthesis of the partial structure 92 of ikarugamycin was achieved [27],... 

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