Allylboranes chiral

The synthesis of chiral a-substituted allylborane 2 via the hydroboration of 1,3-cyclohexa-diene with diisopinocampheylborane has been reported21. 

Although this general principle of asymmetric induction has not been demonstrated for boron enolates, the related addition reactions of allylboranes to aldehydes (eq. [115]) (131) have been examined in this context. The reaction of chiral diol 175 with either triallyl-borane or tri- -methallylborane afforded the boronic esters 176 (Ri = H, Me) in yields exceeding 95% (132a). The addition reactions of 176 to representative aldehydes are summarized in Table 40. In all cases reported, the sense of asymmetric induction from the chiral... 

Advantages of Brown s chiral allylboranes (isopinocampheyl and later caranyl borane) are the easy access to the ligands (a-pinene is a natural product, chiral pool), the availability of both enantiomers and their low price. Excellent selectivities (96-99% ee) can be obtained at reaction temperatures of -100 °C. Other important mediators for enantioselective allylation of aldehydes are shown below.14... 

Chiral addition of allyl metals to imines is one of the useful approaches toward the synthesis of homoallylic amines. These amines can be readily converted to a variety of biologically important molecules such as a-, / -, and y-amino acids. Itsuno and co-workers utilized the allylborane 174 derived from diisopropyl tartrate and cr-pinene for the enantioselective allylboration of imines. The corresponding iV-aluminoimines 173 are readily available from the nitriles via partial reduction using diisobutylaluminium hydride (DIBAL-H) <1999JOM103>. Recently, iV-benzyl-imines 176 have also been utilized for the asymmetric allylboration with allylpinacol boronate 177 in the presence of chiral phosphines as the chiral auxiliaries to obtain homoallylic A -benzylamines 178 in high yield and selectivity (Scheme 29) <2006JA7687>. 

Unsaturated aldehydes are poor substrates for allylation because of their inherent instability toward alkene isomerization accordingly, very few reports describe the allylation of these substrates. However, Lautens et al. were able to overcome this problem via an indirect approach by the use of 2-vinyloxiranes 219 as surrogates for the above-mentioned aldehydes. The in situ formation of these otherwise unstable aldehydes is achieved via the Lewis acid treatment of vinyloxiranes to furnish aldehydes 221 which further undergo allylation with chiral allyl boronates 174 in moderate ee (Scheme 37) <20020L83>. The chiral induction could be further enhanced by the use of allylboranes derived from a-pinene. 

Corey s asymmetric allylation methodology was utilized in the total synthesis of amphidinolide T3 (95), a marine natural product that exhibits significant antitumor properties37 (Scheme 3.1gg). The asymmetric allylation of the aldehyde 96 was carried out successfully with chiral allylborane reagent generated in situ from allyltributylstannane and (R,R)-82 to furnish the homoallylic alcohol desired (97) in 85% yield with excellent diastereoselectivity. Subsequent conversion of the alcohol to the tosylate ester followed by treatment with potassium hydroxide resulted in formation of the trisubstituted tetrahydrofuran 98. 

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. 

Chart 10-4. Terpene-derived chiral allylborane reagents. 

Table 10-13. Reaction of achiral aldehydes with chiral allylborane reagents [125e].

By far the most extensively investigated and most useful of the chiral allyl-and 2-butenylboron reagents are those developed in the Roush laboratories (Chart 10-5) [124j. The tartrate ester-modified allyl- and 2-butenylboronates are attractive alternatives to the allylborane reagents because of their ease of prepara-... 

The transfer of chirality to homoallylic alcohols 240-242 and 272 in the reactions of reagents 195, 220, 212 and 229 with aldehyde substrates is rationalized by C-C bond formation occurring preferentially through transition state 273 (Fig. 11-27). Transition state 274, which leads to the enantiomeric products, is disfavored due to destabilizing steric interactions between the a-methylene and the chiral ligands of the allylborane reagent. 

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). 

Scheme 23 shows how four possible diastereomers can arise from the combination of two sp -carbon centers C-1 and C-2 in a donor component 23-1 and an acceptor component 23-2. Species 23-3 and 23-4 are two diastereomers and 23-5 and 23-6 are their enantiomers.The problem of simple diastereoselection is the control of the diastereomer ratio 23-3-1-23-5/23-4-1-23-6. The enantiocontrol of 23-3 vs 23-5 or of 23-4 vs 23-6 cannot be achieved by simple diastereoselection in this case an external source of chirality has to be applied, for instance a chiral catalyst or the incorporation of stereogenic units in one of the components. Simple diastereoselection can be exerted in terms of closed and open transition states, depending on the mutual interaction of the termini X and Do, respectively. If these termini are linked via a six-membered chelate, a closed ( Zimmerman-Traxler ) transition state 23-7 with synperiplanar olefinic units is formed. On the other hand, if the termini have a repulsive interaction an open transition state 23-8 with an antiperiplanar arrangement of the olefinic units is adopted. Efficient stereocontrol via Zimmerman-Traxler transition states 24-1 to 24-4 is observed in aldol-type and allylborane carbonyl additions (Scheme 24). The crucial stereo differentiating interaction is the diaxial repulsion between Rax and R, which must be kept as low as possible. Only small substituents (nor-...

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). 

R = CH2N(CH2)5) [87], Chiral boranes have been widely developed, and they can be used in reductions and hydroborations [87, 169, 580, 583, 584], CMral allylboranes and enol boronates will be described later ( 2.6 and 2.8). 

The stereoselectivity of the reactions of aldehydes with allylboranes and -boronates bearing chiral substituents on the boron atom depends upon the terminal substituent of the allylic double bond. If the C-3 carbon is symmetrically substituted, dien the products are enantiomers, and if it is unsymmetrically substituted, then diastereoisomers will be formed (Figure 6.42). 

When the allylboranes react with a chiral aldehyde, products with three stereocenters are formed, and two examples of such transformations are given in Figure 6.52 [1211],... 

Corey and coworkers have described Ae preparation of allylborane (289) by the reaction of bromobo-rane (2W) and allyltributylstannane and shown that (289) undergoes highly stereoselective reactions with )x>th achiral (95-97% ee) and chiral aldehydes (Scheme 54). The corresponding methallyl, ( )-crotyl and 2-chloro- and 2-bromo-allyl reagents were prepared by similar methods and shown to give excellent results in reactions with achiral aldehydes (84-99% ee in most cases). 

A particularly useful borane is the chiral reagent (-)-B-allyl(diisopinocampheyl)borane.l 3 Although the chemistry of acyl addition to aldehydes and ketones to give alcohols will not be formally discussed until Section 8.4.C, the addition of this chiral allylborane to carbonyl compounds will be presented here. In a simple example taken from Smith s synthesis of (-)-macrolactin A,n 156 was treated with (-)-B-... 

---