Chiral Allylboronate Reagents

The reaction of triallylborane31 with diols or acidic amino alcohols provides a convenient method of synthesis of allylboron reagents, especially when the diol or amino alcohol is a valuable chiral auxiliary32-34. Two representative cases arc summarized below. 

I.3.3.3.3.I.3. Relative Asymmetric Induction Reactions of Chiral Aldehydes with Achiral Allylboron Reagents... 

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. 

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 ... 

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. 

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. 

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

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. 

The tartrate-derived allylboronate reagents in the best cases compare favorably with other allylboration reagents in their reactions with both achiral and chiral aldehydes (e.g. B-Allyldi-... 

Related Allylboronate Reagents. A stereoselective synthesis of anti 1,2-diols has been achieved by using a DIPT-modified ( )-y-[(cyclohexyloxy)dimethylsilyl]allylboronate reagent. This reagent is best applied in double asymmetric reactions with chiral aldehydes such as o-glyceraldehyde acetonide (eq 9). 

A chiral allylic alcohol (3-carbanion equivalent has also been developed which utilizes a DIPT-modified E)-y-(dimethylphenylsilyl)allylboronate reagent. This method involves treating the product homoallylic alcohol with Dimethyl-dioxirane and subjecting the derived epoxide to an acid-catalyzed Peterson elimination. This sequence has been applied in the synthesis of the trioxadecalin ring system of the mycalamides (eq 10). ... 

Roush, W. R., Grover, P. T., Lin, X. Diisopropyl tartrate modified (E)-y-[(cyclohexyloxy)dimethylsilyl]allylboronate, a chiral reagent for the stereoselective synthesis of anti 1,2-diols via the formal a-hydroxyallylation of aldehydes. Tetrahedron Lett. 1990, 31,7563-7566. 

Reagents developed for the synthesis of 2-anti diol adducts include the chiral [( )-7-alkoxyallyl]indium and [( )-7-alkoxyalIyl]boronate reagents 233 [171J and 234 (Fig. 11-21) [172]. Alternatively, the ( )-allylboron reagents 235-237, which included silicon and boron substituents as hydroxy sunogates, have been independently developed [173-177]. 

Corey and co-workers developed the highly enantioselective allylboron reagent 198 [127], whose chiral 1,2-diamino-1,2-diphenylethane (stein) auxiliary [254] serves as the source of asymmetry. In an extension of this methodology, Williams et al. have demonstrated the utility of the bromoborane 332 for the preparation of synthetically complex allylborane reagents [255] and have applied this methodology in two natural product syntheses [256, 257] (see below). 

The efficient transmetalation of allylic stannanes to allylboron reagents has generated an attractive methodology for asymmetric allylation. Corey and coworkers first described the use of enantiomers of bromoborane 228 (Scheme 5.2.51) for mild and quantitative transmetalation of allylstannane to yield the allylboron reagent 229. i The asymmetry in the bis-toluenesulfonamide of 228 is derived from l,2-diamino-l,2-diphenylethane, and both antipodes are readily available in high optical purity, by resolution of the starting diamines producing (R,R)- and (5, 5 )- Stein chiral auxiliaries in transmetalation product 229. 

The first example of enantioselective allylation of an azomethine function was reported in 1995 by Itsuno and co-workers [42a]. These researchers studied the addition of preformed chirally modified allylboranes to N -(trimethylsilyl)ben-zaldehyde imine (5a) (<2 g of imine, ca. 0.27 M). Of the wide range of chirally modified allylboron reagents reported in the literature, the use of chiral allylbo-ronates 42a-c and 5-allyldialkylborane 43 were logical first choices given their utility in the enantioselective addition to carbonyl substrates (Scheme 20). 

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

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." ... 

If the presence of sensitive functional groups poses problems of chemoselectivity in the use of hard allylmetal reagents, allylboronate derivatives can also be accessed by transmetallation of allyltin species with boron halides [29], This approach was used by Corey in the synthesis of chiral bis(sulfonamido)boron reagents (Section 6.3.1.3) [30]. Recently, Williams and co-workers employed this mild approach to synthesize the highly functionalized allylboron reagent 9, which was employed in a key aldehyde allylboration reaction en route to the total synthesis of leucasdandrolide A (Equation 5) [31]. 

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