Asymmetric allylation allylboron

The thiazole-substituted homoallylic alcohol 25 (Scheme 6) is a key intermediate, not only for RCM strategies, but also for other routes. Thiazole aldehyde 4 (Chapter 3) after homologation to enal 24 (90 % yield) [ 11,20) was subjected to asymmetric allylation with allylboron and tin reagents. Interestingly 25 with identical absolute stereochemistry was synthesized by Nicolaou et al. with (+)-IpC2B(allyl) in 96 % yield and > 97 % ee [13, 20], and by Danishefsky et al. with the enantiomeric (—)-Ipc2B(allyl) in 83 % yield and > 95 % ee [11], i.e. in one case an er-... 

The total synthesis of the 20-membered macrolide (+)-lasonolide-A was undertaken by S.H. Kang and co-workers. During the construction of the C15-C25 subunit, they utilized the Roush asymmetric allylation reaction to introduce the C21 and C23 stereocenters. First, (R,R)-diisopropyltartrate derived allylboronate was used to provide the (S)-homoallylic alcohol with 78% ee. A second asymmetric allylation was achieved utilizing the (S,S)-diisopropyltartrate-derived allylboronate to form the (R)-homoallylic alcohol with a 91% ee. 

Roush asymmetric allylation Reaction of allylboronates with aldehydes to give homoallylic alcohols. 386... 

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. 

Several catalytic asymmetric allylation reactions have been developed specifically for iminoester derivatives, but the level of enantioselection remains typically only in the lowto high 80s (Table 1.15). Allylstannanes [99], allylsilanes [100], allyltrimethox ysilanes [101], and allylboronates [102] are suitable nucleophiles in these copper or zinc catalyzed processes. 

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.). 

In the second approach, allylboronation of 9 with 10 led to the predominant formation of 8a which was transformed to 6a (R = H). The allylic alcohols 5a and 5b prepared from 6a and 6b, respectively, were subjected to asymmetric epoxidations307, each with (-f)-DET and (—)-DET, to provide four diastereomers. One of them, 4b, was identical with degradation product 2. Note that in these reactions double stereodifferenlialion (see Section A.2.3.5.4.) is operating (for configurational assignment at C-15, see p431)244. 

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 last class of allylation reactions that are amenable to asymmetric catalysis employs allylboronate derivatives. Schaus reported that several chiral BINOL deri vatives catalyze the enantioselective asymmetric allylboration of acyl imines [97]. This reaction is most effective when 3,3 diphenyl BINOL acts as the catalyst and allyldii sopropoxyborane is the nucleophile. The allylation products are obtained in good yields (75 94%) and excellent enantiomeric excesses (>90% ee) for both aromatic and aliphatic imines (Table 1.13). 

By a similar method, the (Z)-crotylborate is synthesized from cA-2-butene in 70-75% yield with a 98% isomeric purity. The tartrate esters of allylboronic acids are an excellent reagent for asymmetric allylboration of carbonyl compounds. Allyl(diisopinocampheyl)borane [51] and the allylic boron derivatives of ester and amide, such as camphordiol [52], pinanediol [53], 1,2-diphenyl-1,2-ethylenediamine [54], have also been successfully used for asymmetric allylboration of carbonyls. 

The first examples of highly diastereoselective double asymmetric reactions involving chiral allyl metal reagents were obtained in reactions with D-glyceraldehyde acetonide (151 Table 6). Aldehyde (151) displays an 80 20 preference for (154) in reactions with the achiral pinacol allylboronate (144 entry 4),25.ioi selectivity for (154) improves to 96-98% with reagents (-)-(215) and (RJi)-... 

The addition of allyl and prenyl organometallics (84) to 8-(-)-phenylmenthyl A/-methoxyiminoacetate (83 equation 19) has been examined for the asymmetric synthesis of amino acids. Treatment of (83) with allylboronates and allylzinc bromide affords N-alkoxyamines (85) and (86 Table 19). Both allyl-... 

Ultimately, after appropriate functional adjustments, tetrahydrolipstatin was obtained in 38% overaU yield from the P-benzyloxyaldehyde in seven steps. The route starting from lauraldehyde via allylation and resolution, or via asymmetric allylboronation (84% ee at -78 C) comprises 10 steps and 26% overall yield. Although the above outlined synthesis is short in number of steps and quite efficient, it is not clear if it meets the cost effective conditions required for large scale production of tetrahydrolipstatin, particularly because of the low temperature required for some reactions. 

Originally, enantiosdective allylboration was developed using chiral allylbo-ranes and allyl boronates. These reactions require multistep preparahons of chiral reagents that are used in stoichiometric amoimts, and are therefore impractical. Recently, catalytic asymmetric allylborations were developed. These reactions can apply either chiral Lewis bases or BBonsted acids as the catalysts, hi particular, chiral BlNOL-phosphoric acids were demonstrated to provide high optical yields in the enantioselective allylboration reaction between allylboronate 1 and aldehydes. For example, the catalytic asymmetric allylboration of benzaldehyde 2 proceeded quantitatively yielding the corresponding homoallyl alcohol 3 with 98% ee ( heme 3.1). 

---