Boronate allyl, enantioselective addition reactions

Allylic t ganranetallics modified at the metal center by chiral adjuvants add to aldehydes and ketones to provide optically active hranoallylic alcohols. This process has been described for reagents containing boron, tin and chromium metd centers. Gore and coworkers have shown that a chrranium-medi-ated addition reaction of allylic brranides to simple aldehydes that uses a complex of lithium N-methyl-nt ephedrine and chromium(Il) chloride occurs with modest (6-16% ee) enantioselectivity (equation 61, Table 8). 

Addition reactions. Asymmetric allyl transfer from allyl boronates to A-acyl imines is assisted by (5)-3,3 -diphenyl-BINOL Alkenyldimethoxyboranes react with conjugated carbonyl compounds with excellent enantioselectivity in the presence of a chiral 3,3 -diiodo-BINOL. ... 

In order to explain the chemistry of allylic metals, the reactions of allylic boron compounds [8,12-14] are covered in detail. The boron chemistry is divided into four parts simple enantioselectivity (addition of CH2=CHCH2-, creating one new stereocenter), simple diastereoselectivity of crotyl additions (relative configuration after CH3CH=CHCH2- addition, where neither reagent is chiral), single asymmetric induction with chiral allyl boron compounds (one and two new stereocenters), and double asymmetric induction (both reactants chiral, one and two new stereocenters). Then follows a brief discussion of other allyl metal systems. 

The enantioselective addition of allyl 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, 200.3) the scandium triflate catalysis chiral allylboronic acids become more effective tools. The best of these, the Hoffmann camphor derivative 2, adds to aldehydes under ScfOTOj 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. 

Other enantiomerically pure B-allylboranes also show excellent stereoselectivity in these reactions." Allyl and 2-butenyl derivatives of the cyclic boronate ester 3, derived from tartaric acid, also give enantioselective additions to aldehydes. ... 

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 ). 

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. 

Figure 5.1 lists a number of auxiliaries for asymmetric allyl addition to aldehydes. Substituted allyl boron compounds have also been used in reactions with achiral aldehydes. Table 5.1 lists several examples of 2- and 3-substituted allyl boron compounds, and the products derived from their addition. Note that for the E- and Z-crotyl compounds, the enantioselectivity indicated is for the isomer illustrated. In some cases, there was more than one of the other three possible isomers found as well. 

Recently, Shibasaki and co-workers reported a copperreaction using a chiral diphosphine ligand, DuPHOS, with an added lanthanide salt (118]. This new allylation system provides good levels of enantioselectivity in additions of the simple allylboronate 2 to either aromatic or aliphatic ketones that present a large difference of steric bulk on both sides of the carbonyl (Equation 43). Based on NMR experiments and on the lack of diastereoselectivity in crotylation examples, the suggested mechanism of this allylation involves transmetallation of the boron to an allylcopper species. 

Enantioselective synthesis of homopropargyl amines can be effected through copper-catalysed reaction of an allenyl boron reagent with aldimines. The first nucleophilic allylation of r-electrophiles by allylboron reagents has been achieved enantioselectively using a chiral rhodium catalyst (Scheme an allylrhodium intermediate has been implicated. Similar additions of R CH=CR BF3K have also been reported. ... 

The additions of allyl-, crotyl-, and prenylborane or -boronate reagents to aldehydes are among the most widely studied, well developed, and powerful reactions in stereoselective synthesis. The additions not only display excellent levels of absolute induction in enantioselective synthesis, but also exhibit superb levels of reagent control in diastereoselective additions. The additions of ( )- or (Z)-crotyl pinacol boronates to aldehydes have been observed to give predominantly 1,2-anti- and 1,2-syn-substituted products, respectively (Scheme 5.3) [31, 50]. The inherent stereospecificity of the reaction is consistent with a closed, cyclic Zimmerman-Traxler transition state structure [51], In the accepted model, coordination of the aldehyde to the allylation reagent results in synergistic activation of both the electrophile and the nucleophile... 

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