Crotylboranes

A valuable asymmetric route to homoallylic alcohols exploits the remarkably versatile chemistry of boranes.t ] The (Z)- and E)-crotylboranes (37) and (38) are prepared by reaction of the corresponding (Z)- and )- crotyl potassiums with (+)- or (-)-methoxydiisopino-campheylborane (36), (also known as IpC2BOMe), 

Aldehydes react smoothly with these crotylboranes via a six-membered Zimmerman-Traxler type transition state (39), giving homoalkylic alcohols (40) with high enantioselectivity and essentially complete diastereoselectivity. 

By the appropriate choice of alkene geometry and chirality of pinene, it is possible to make either enantiomer of either diastereomer at will. For further applications of chiral boranes, see section 6.4. 

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TABLE 3-11. Reaction of Crotylboranes (E,R,R)-i 15 and (Z,R,R)-115 with Representative Achiral Aldehydes... 

Entry Crotylborane Aldehyde Yield (%) anti/syn Ratio Major Product ee (%)... 

The two (Z)-crotylboranes react with typical aldehydes to give syrt-0-methyl-homoallyl alcohols with high diastereo- and enantioselectivity (equation I), whereas the (E)-crotylboranes provide a useful route to the anr/ -homoallylic alcohols (equation II). Thus by proper choice of the crotylborane, any one of the four possible... 

Figure 2. Comparison of the stereochemical stability of crotylboranes vs crotylboro-nates.

Chiral Dialkylboranes. Several allylic boranes have been developed as chiral auxiliary reagents (Fig. 5). The introduction of terpene-based reagents such as 12 and 64-68 has been pioneered by H.C. Brown, and the most popular class remains the bis(isopinocampheyl) derivatives (structures 12, 64-66). A wide variety of substituted analogs have been reported, including the popular crotylboranes but also a number of other reagents bearing heteroatom-... 

Kinetic resolution can be accomplished by addition of allyl boronates to aldehyde groups adjacent to the tricarbonyliron fragment [59]. For the synthesis of ikaruga-mycin, Roush and Wada developed an impressive asymmetric crotylboration of a prochiral meso complex using a chiral diisopropyl tartrate-derived crotylborane (Scheme 1.25) [60]. In the course of this synthesis, the stereo-directing effect of the tricarbonyliron fragment has been exploited twice to introduce stereospedfically a crotyl and a vinyl fragment. 

Diisopropyl crotylboronates, 1. These chiral crotylboranates are prepared in 98-99% ee from diisopropyl tartrate. 

Explain the diastereoselectivity observed in the (Ej-crotylborane addition to aldehyde 4. 

Allyl- and crotylborane aldol transition state Vulpetti 1993b... 

From the range of synthetic applications of Brown s pinene-derived allyl- and crotylborane reagents illustrated in these selected examples, it is clear that they are excellent reagents for the synthesis of chiral homoallylic alcohols from chiral and achiral aldehydes alike. That so many researchers have applied these reagents in their research also attests to the great utility of these reagents in organic synthesis. 

In the final analysis, it appears that the diastereoselectivity of the reactions of imines and crotylboranes (47, 96) depends on the relative rates of crotyl transfer e.g. 95a —> 93) versus imine isomerization that leads to competitive pathways (e.g. 94d - 92). When R is an aryl group, the rate of crotyl transfer is probably faster than competitive imine isomerization. When R is an alkyl group, however, the relative rates are probably inverted. The driving force for imine isomerization is probably that complex (95a) is not very stable owing to the bulky 9-BBN unit positioned syn to R, while the complex of crotyl-9-BBN (47) and a (Z)-aldimine e.g. 94d) is probably much more stable. It is conceivable, therefore, that the overall rate of reaction via (94d) can be much faster than via (95a) even though the (Z)-imine cannot be detected in solution. Additional research is clearly needed to clarify the stereochemical course of these reactions. 

Alkoxycarbonylative cyclization of 39 was attempted in methanol under an atmosphere of CO in the presence of a catalytic quantity of PdCl2 with CuCl2 as stoichiometric oxidant (Table 1). To our surprise, not even a trace of the desired tetrahydropyran 40 was formed. Three additional 6-hydroxy-1-octenes, 41, 43, and 45, were prepared from 34 by using the appropriate isomer of crotylborane 37 in each casc. Under identical reaction conditions to those previously tested with 39, alkoxycarbonylation of these isomers gave varying amounts of the expected 2,6-c/5-tetrahydropyran products (Table 1). Evidently,... 

The reaction proceeds with excellent enantioselectivity as shown, but in some cases the diastereoselectivity is modest, which is true when the allylborane reagent is substituted, as in crotylborane derivatives. In the Omura, Smith and co-workers synthesis of (+)-lactacystin, for example, reaction of the B-crotyl derivative shown with aldehyde 158 gave a 4 1 mixture of 159 and 160 in high yield. Each diastereomer was formed with high enantioselectivity. 

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