Chiral allylboronates synthesis

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. 

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 ... 

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. 

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

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... 

Waldmann and coworkers later developed and explored the solid-supported carbonyl allylation reactions for the stereoselective solid-phase synthesis of a collection of NP-inspired 8-lactones. To identify reaction conditions that would give rise to the allylation products with high enantioselectivity and in high yield, immobilized aldehyde 26 was synthesized as model compound and was then subjected to allylation with different chiral allylboron reagents. After some experimentation, it was found that treatment of the resin-bound aldehyde with 4 equiv of D-Ipc2BAll 28 at 78°C in THF/ether 5 1 (v/v) followed by... 

Hoffmann has published full details of his diastereoselective synthesis of homoallylic alcohols from crotyl boronates (c/. 4, 149) and aldehydes (Scheme 24). In results consistent with the rationalization presented above, -boronates gave rhreo-alcohols and Z-boronates gave the erythro-diastereomer with virtually complete diastereoselectivity, i.e. threo erythro ratios in the products mirroring the E Z ratio in the starting boronates. A full account has also appeared of work by the same group on addition of chiral allylboronates such as (33) to aldehydes to produce optically active homoallylic alcohols (Scheme 25) cf. 3, 143), with approx. 70% e.e. in the case of saturated aldehydes and having the configumtion as illustrated. "... 

Optically active allylboronates bearing chiral auxiliary located at the boron atom found widespread applications in asymmetric synthesis. Enantiomerically enriched a-alkylidene-y-lactones and lactams can also be synthesized following such a synthetic approach. VUlieras et al. (41, 45] demonstrated the potential of chiral allylboronates derived from 2-phenyl-2,3-bomanediol, ephedrine, or norephedrine for this purpose. Chiral allylboronates 46a,b were obtained in a sequence of reactions involving transformation of achiral precursors 32 into the corresponding boronic acids 44 followed by their esterification with enantiomerically pure diol or 1,2-aminoalcohol 45 (Scheme 4.10). In the case of methyl-substituted derivatives 32b (R = Me), initial composition of E- and Z-isomers was transferred to the target allylboronates 46b. Importantly, the isomeric mixture was separated by means of the column chromatography. 

Hoffmann RW. a-Chiral allylboronates reagents for asymmetric synthesis. Pwre A/)/)/. Chem. 1988 60 123-130. 

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. 

In spite of the poor diastereoselectivity realized in reactions with most chiral aldehydes, allylboronates are highly attractive reagents for organic synthesis.. i. 2,17 i ost are easily prepared in large quantities, and are convenient to use. 8 They are nonbasic, relatively non-nucieophilic, and hence are highly chemoselective in their reactions. 

We began these studies with the intention of applying this tandem asymmetric epoxidation/asymmetric allylboration sequence towards the synthesis of D-olivose derivative 63 (refer to Figure 18). As the foregoing discussion indicates, our research has moved somewhat away from this goal and we have not yet had the opportunity to undertake this synthesis. This, as well as the synthesis of the olivomycin CDE trisaccharide, remain as problems for future exploration. Because it is the enantioselectivity of the tartrate ester allylboronates that has limited the success of the mismatched double asymmetric reactions discussed here, as well as in several other cases published from our laboratorythe focus of our work on chiral allyiboronate chemistry has shifted away from synthetic applications and towards the development of a more highly enantioselective chiral auxiliary. One such auxiliary has been developed, as described below. 

If the presence of sensitive functional groups poses problems of chemose-lectivity in the use of hard allylic metal reagents, allylboronate derivatives also can be accessed by a milder transmetalation of allylic tin species with boron halides.This approach has been used by Corey in the synthesis of chiral bis(sulfonamido)boron reagents such as the medially 1 reagent 15 (Eq. 19) (see section Chiral Boronate Derivatives ). ... 

Complexes of unsymmetrically substituted conjugated dienes are chiral. Racemic planar chiral complexes are separated into their enantiomers 84 and 85 by chiral HPLC on commercially available /f-cyclodextrin columns and used for enantioseletive synthesis [25]. Kinetic resolution was observed during the reaction of the meso-type complex 86 with the optically pure allylboronate 87 [26], The (2R) isomer reacted much faster with 87 to give the diastereomer 88 with 98% ee. The complex 88 was converted to 89 by the reaction of meldrum acid. Stereoselective Michael addition of vinylmagnesium bromide to 89 from the opposite side of the coordinated Fe afforded 90, which was converted to 91 by acetylation of the 8-OH group and displacement with EtjAl. Finally, asymmetric synthesis of the partial structure 92 of ikarugamycin was achieved [27],... 

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. Diisopropyl tartrate (E)-Y-(dimethylphenylsilyl)allylboronate, a chiral allylic alcohol 3-carbanion equivalent for the enantioselective synthesis of 2-butene-1,4-diols from aldehydes. Tetrahedron Lett. 1990, 31,7567-7570. 

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]. 

Results of reactions of chiral a-methyl aldehydes and several chiral crotyl- and allyl-boron reagents are summarized in Tables 8 and 9. It is apparent from these data that the Brown (Ipc)2B(crotyl) and (Ipc)2B(allyl) reagents (51), (52) and (219) consistently give excellent results for the synthesis of each product diastereomer (Table 8, entries 3-6, 11, 16, 20, and 24 Table 9, entries 1,2, 10 and 18). This is true also for their reactions with chiral a- and 3-alkoxy aldehydes (Scheme 49).i. i4S-i50 Thg tartrate crotylboronates (18) and (19) also display excellent selectivity in the synthesis of crotyl diastereomers (136), (137) and (139) (Table 8, entries 7,10,13,17,25 and 28), but are much less selective for the syndesis of crotyl diastereomer (138), especially from -alkoxy-substituted aldehydes such as (253). Tartrate allylboronate (224) is also less effective than (Ipc)2Ballyl (219) for the synthesis of (257) and (258) in Table 9, and of (266) and (267) in Scheme 49.Substantial improvements in selectivity have been realized by using the taitramide-based allylboronate (228), and the results with this reagent (Table 9, entries 4, 7, 9, 12, 14, 17, 20 and 22) compare very favorably with those obtained with (219). The data... 

The allylation and crotylation of a-alkoxy aldehydes provide chiral 1,2-diol synthons which can be used in the synthesis of polyoj genated small molecules, for example, natural and unnatural sugars The tartrate-derived allylboronates I and 2 provide reagent-controlled selectivity in reaction with chiral glyceraldehyde acetonide 30. The intrinsic selectivity of the aldehyde is estimated by its reactions with pinacol allylboronates 33 and 34. The reagents 1 and 2 overcome the aldehyde s... 

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