Chiral allylboronates

The enantioselectivities of the reactions of representative achiral aldehydes and chiral allylboron reagents arc compared in Table 4. A comparison of the enantioselectivities of the (Z )-2-butenyl reagents appears in Table 5, while Table 6 provides a similar summary of the reactions of the (Z)-2-butenyl and 3-methoxy-2-propcnyl reagents. A 3-diphenylamino-2-propenyl reagent was recently reported102. 

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

I.3.3.3.3.I.5. Double Asymmetric Induction Reactions of Chiral Aldehydes with Chiral Allylboron Reagents... 

On the other hand, high levels of diastereoselectivity are relatively easy to achieve in matched double asymmetric reactions since the intrinsic diastereofacial preference of the chiral aldehyde reinforces that of the reagent, and in many cases it has been possible to achieve synthetically useful levels of matched diastereoselection by using only moderately enantioselective chiral allylboron reagents. Finally, it is worth reminding the reader that both components of double asymmetric reactions need to be both chiral and nonracemic for maximum diastereoselectivity to be realized. 

Many of the chiral allylboron reagents discussed in Section 1.3.3.3.3.1.4. have been utilized in double asymmetric reactions with chiral aldehydes. Chiral 2-(2-butenyl)-3.5-dioxa-4-boratri-cyclo[5.2.1.02-6]decanes were among the first chiral reagents of any type to be used in double asymmetric reactions52a,b. 

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

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). 

The poor diastereoselectivity of the reactions of chiral aldehydes and achiral allylboronates appeared to be a problem that could be solved by recourse to the strategy of double asymmetric synthesis.f Our studies thus moved into this new arena of asymmetric synthesis, our objective being the development of a chiral allylboron reagent capable of controlling the stereochemical outcome of reactions with chiral aldehydes independent of any diastereofacial preference on the part of the carbonyl reaction partner. 

Results obtained in reactions of the chiral allylboronates with cyclohexanecarboxaldehyde. 

Our development of the tartrate ester modified allylboronates c.h suggested to us that many of these problems could be avoided by using the reaction of a chiral aldehyde and a chiral allylboronate as a means of establishing the stereochemistry of the sugar backbone. This strategy has been used in our synthesis of the AB disaccharide unit of olivomycin A (Figures 16, 17).3 ... 

Another useful chiral allylboron reagent is derived from jV,7V-bis(/j-tolucncsulfonyl)-... 

The reaction of 2-(l-alkyl-2-alkenyl)-l,3,2-dioxaborolancs with a suitably chosen aldehyde resulting in further C—C bond formation with chirality transfer is described in Section D.1.3.3.3.3. A number of analogous reactions of chiral allylboronic esters with aldehydes are described there as well. 

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. 

Enantiomerically pure homoallylic amines are very important chiral building blocks for the synthesis of natural products. However, enantioselective methods for homoallylamine are quite undeveloped. In 1995, Itsuno and co-workers reported the first example of enantioselective allylation of an imine (Scheme 7) [13]. The reaction of N-trimethylsilylbenzaldimine 19 with a chiral allylboron reagent 20 in ether at -78 °C afforded the corresponding homoallylamine 22 in 73% ee. 

Several methods promoted by a stoichiometric amount of chiral Lewis acid 38 [51] or chiral Lewis bases 39 [52, 53] and 40 [53] have been developed for enantioselective indium-mediated allylation of aldehydes and ketones by the Loh group. A combination of a chiral trimethylsilyl ether derived from norpseu-doephedrine and allyltrimethylsilane is also convenient for synthesis of enan-tiopure homoallylic alcohols from ketones [54,55]. Asymmetric carbonyl addition by chirally modified allylic metal reagents, to which chiral auxiliaries are covalently bonded, is also an efficient method to obtain enantiomerically enriched homoallylic alcohols and various excellent chiral allylating agents have been developed for example, (lS,2S)-pseudoephedrine- and (lF,2F)-cyclohex-ane-1,2-diamine-derived allylsilanes [56], polymer-supported chiral allylboron reagents [57], and a bisoxazoline-modified chiral allylzinc reagent [58]. An al-lyl transfer reaction from a chiral crotyl donor opened a way to highly enantioselective and a-selective crotylation of aldehydes [59-62]. Enzymatic routes to enantioselective allylation of carbonyl compounds have still not appeared. 

Chiral a-carbamoyloxy-2-alkenylboronates react with Grignard reagents with complete a- and diastereoselectivity through rearrangement of an intermediate ate -complex, yielding chiral allylboronates, which were oxidized to... 

Hoffmann, R. W., Herold, T. Enantioselective synthesis of homoallyl alcohols via chiral allylboronic esters. Angew. Chem. Int. Ed. 1978,17, 768-769. 

Uncatalyzed Additions of Nucleophilic Alkenes to C X Table 9 Reactions of a-Methyl Chiral Aldehydes and Chiral Allylboron Reagents... 

A combination of organocatalysts, the prolinol silylether 17b and an A-heterocyclic carbene (NHC), was used by Cordova and co-workers [64] for the related asymmetric P-boration of cinnamaldehyde. While the secondary amine served to activate the enal through the formation of a chiral iminium ion intermediate, the NHC functioned as a Lewis base forming the nucleophilic adduct with diborate. The product was treated in situ with a stabilized phosphorus ylide affording a synthetically useful chiral allylboronate (Scheme 14.22). A 50 mol% loading of amine was needed to reach reasonable enantioselectivity (60% ee). Lowering of the amine loading to 10 mol% caused a drop in the enantioselectivity (34% ee). 

The scope of enantioselective, copper-catalyzed allylic substitution reactions is not limited to so-called hard carbon nucleophiles and achiral acyclic linear electrophiles. A recent report from Ito, Sawamura, and co-workers showed that a diboron reagent can serve as a pronucleophile for enantioselective, copper-catalyzed boronation of (Z)-aUylic carbonates (Equation 20.85). The corresponding chiral allylboronates were isolated in good yields with high enantioselectivities. 

Another useful chiral allylboron reagent is derived from iV -bis(/ -toluenesulfonyl)-1,2-diphenyl-1,2-ethanediamine. This reagent gives homoallylic alcohols with >90% e.e. with typical aldehydes." ... 

Burgi-Dunitz angle of 107°, passing the least sterically hindering a-substituent in its approach (transition state E). In the double asymmetric reactions of a-chiral aldehydes with chiral allylboronates 1-3, the a-stereocenter and the chiral boronate auxiliary both influence the stereochemical outcome of the reaction. 

The addition of allylboronates to aldehydes was first discovered in 1974 [429]. This reaction has since found tremendous use in the stereoselective synthesis of acetate and propionate units embodied in numerous natural products (Equation 76, Figure 1.39) [430]. The tartrate-based chiral allylboronates, for example, have become one of the... 

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