Homoallylic alcohol substrate, asymmetric

Striking examples of this phenomenon are presented for allyl and homoallyl alcohols in Eqs. (5) to (7). The stereodirection in Eq. (5) is improved by a chiral (+)-binap catalyst and decreased by using the antipodal catalyst [60]. In contrast, in Eq. (6) both antipode catalysts induced almost the same stereodirection, indicating that the effect of catalyst-control is negligible when compared with the directivity exerted by the substrate [59]. In Eq. (7), the sense of asymmetric induction was in-versed by using the antipode catalysts, where the directivity by chiral catalyst overrides the directivity of substrate [52]. In the case of chiral dehydroamino acids, where both double bond and amide coordinate to the metal, the effect of the stereogenic center of the substrate is negligibly small and diastereoface discrimination is unsuccessful with an achiral rhodium catalyst (see Table 21.1, entries 9 and 10) [9]. 

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. 

A considerable success has been realized for asymmetric hydrogenation of functionalized alkenes since the discovery of BINAP-Ru complexes in the mid-1980s [5]. The details are described in each of the following substrates, enamides, alkenyl esters and ethers, a,/3- and /3,y-unsaturated carboxylic acids, a,/3-unsaturated esters and ketones, and allylic and homoallylic alcohols. 

A. Furstner and co-workers devised an efficient synthesis of (-)-gloeosporone, a fungal germination inhibitor. They utilized the Keck asymmetric allylation method to create the 7(R>homoallylic alcohol subunit. The reaction of the substrate aldehyde in the presence of the in situ generated catalyst provided the product with high yield and as the only diastereomer. It is important to note that it was essential to use freshly distilled Ti(/-OPr)4 for the preparation of the catalyst in order to get high enantioselectivity and reproducible results. 

The first asymmetric total synthesis of (+)-astrophylline was accomplished in the laboratory of S. Blechert. The Still variant of the [2,3]-Wittig rearrangement was used to generate the 1,2-trans relationship between the substituents of the key cyclopentene intermediate. The tributylstannylmethyl ether substrate was transmetalated with n-BuLi, which initiated the desired [2,3]-sigmatropic shift to afford the expected homoallylic alcohol as a single enantiomer. 

Generally the reaction of unsaturated aldehydes (aromatic, olefmic and acetylenic) with chiral boronates has provided homoallylic alcohols in low to moderate enantioselectivity [124]. However, the enantioselectivity of the allyl- and 2-bu-tenylborations of benzaldehyde and unsaturated aldehydes is significantly improved when a metal carbonyl complex is utilized as the substrate [131]. For example, the reaction of iron carbonyl-complexed diene 225, chromium carbonyl-complexed benzaldehyde 226 and dicobalt hexacarbonyl-complexed acetylene 227 all give significantly increa.sed allyl and 2-butenylboration selectivities compared to the parent aldehydes (Fig. 10-6). In the case of chiral substrates 225 and 226, these species can be obtained in enantioenriched form by kinetic resolution by use of the asymmetric allylboration reaction. 

Of the BINOL/BINAP-metal catalyst complexes, only the allylation procedure described by Keck using the BINOL-Ti(IV) catalyst 451 has been applied in the synthesis of natural products, presumably because it has the most substrate generality and the field is so new. In a preliminary report, Evans disclosed the synthesis of the 4-hydroxy buteneolide terminus 470 of mucocin, where he uses Keck s original catalytic asymmetric allylation procedure to effect conversion of aldehyde 469 to the homoallylic alcohol 470 in good yield and high diastereoselectivity (Scheme 11-36) [312]. 

Mechanistically related to the Mukaiyama aldol reaction, the carbonyl ene reaction is the reaction between an alkene bearing an allylic hydrogen and a carbonyl compound, to afford homoallylic alcohols. This reaction is potentially 100% atom efficient, and should be a valuable alternative to the addition of organometallic species to carbonyl substrates. However, the carbonyl ene reaction is of limited substrate scope and works generally well in an intermolecular manner only with activated substrates, typically 1,1-disubstituted alkenes and electron-deficient aldehydes (glyoxylate esters, fluoral, a,p-unsaturated aldehydes, etc.), in the presence of Lewis acids. The first use of chiral catalyst for asymmetric carbonyl ene was presented by Mikami et al. in 1989. ° By using a catalytic amount of titanium complexes prepared in situ from a 1 1 ratio of (rPrO)2titaniumX2 (X = Cl or Br) and optically pure BINOL, the homoallylic alcohols 70a,b were obtained in... 

Allylic alcohols also provide a suitably activated substrate for hydrogenation. Ryoji Noyori s asymmetric reduction of the prochiral geraniol (E-double bond geometry) and nerol (Z-double bond geometry) to enantiomerically pure citronel-lol in the presence of Ru(OAc)2 BINAP is a well-known example. The nonallylic olefin is not reduced appreciably, which indicates the importance that the allylic alcohol functionality plays in this reduction. (Homoallylic alcohols are also reduced by this system, but when the olefin in question is three or more bonds distant from the alcohol moiety, the compound is inert.) Either enantiomer of cit-ronellol is accessible regardless of which substrate is used depending on the chirality of the Ru-BINAP catalyst used (8). This type of relationship implies that the reaction s mechanism possesses high facial selectivity. 

Cha also explored substrate directed asymmetric synthesis using the Kulinkovich reaction. Sequential treatment of homoallylic alcohol 21 with Ti(0/-Pr)4 and c-C5H9MgCl furnished the putative intermediate 22, which upon exposure to ethyl acetate produced /ra s-l,2dialkylcyclopropanol 23 in... 

Mechanistic studies on the Sharpless asymmetric epoxidation, Eq. (8), where DIPT is diisopropyl tartrate, have been published.The rate law in CH2CI2 is first-order in substrate, catalyst, and oxidant, and shows an inverse second-order dependence on the inhibiting alcohol, in this case Pr OH. This is consistent with a mechanism in which both substrate and the peroxide displace Pr O to form a key intermediate in the reaction. [Differences in the selectivities of allylic and homoallylic alcohols in this reaction have been exploited to invert the expected enantioselectivity. ... 

An asymmetric version of aminoallylation has been developed via a transfer aminoallylation protocol. This methodology involves the initial aminoallylation of camphorquinone 207 with 5-allylpinacol boronate 177 in alcoholic ammonia, furnishing the a-aminoketone 208 stereoselectively, which upon treatment with an aldehyde 209 and achiral allyl boronate 177 leads to the in situ formation of chiral imine 210 followed by allylation to yield the homoallylic amines 212 (Scheme 35) <2006JA11038>. Excellent levels of enantio- and diastereo control were observed for the allylation of a wide array of aldehyde substrates. 

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