Homoallylic alcohols, enantioselective

An unprecedented nickel-catalyzed reductive coupling between an epoxide and an alkyne to give synthetically useful homoallylic alcohols has been developed by Jamison [55a], and was recently used in a short enantioselective synthesis of am-... 

Improved methods for the preparation of reagents such as isopinocampheyl(l-isopinocam-pheyl-2-alkenyl)borinic acids will certainly lead to a more enantioselective synthesis of anti-homoallylic alcohols, since the enantiomeric purity of the reagent is the only significant limitation to the synthetic utility of this reagent system. 

An (E)-selective CM reaction with an acrylate (Scheme 61) was applied by Smith and O Doherty in the enantioselective synthesis of three natural products with cyclooxygenase inhibitory activity (cryptocarya triacetate (312), cryptocaryolone (313), and cryptocaryolone diacetate (314)) [142]. CM reaction of homoallylic alcohol 309 with ethyl acrylate mediated by catalyst C led (E)-selectively to d-hydroxy enoate 310 in near quantitative yield. Subsequent Evans acetal-forming reaction of 310, which required the trans double bond in 310 to prevent lactonization, led to key intermediate 311 that was converted to 312-314. 

Ruthenium complexes containing this ligand are able to reduce a variety of double bonds with e.e. above 95%. In order to achieve high enantioselectivity, the reactant must show a strong preference for a specific orientation when complexed with the catalyst. This ordinarily requires the presence of a functional group that can coordinate with the metal. The ruthenium-BINAP catalyst has been used successfully with unsaturated amides,23 allylic and homoallylic alcohols,24 and unsaturated carboxylic acids.25... 

Reaction of allylic silanes with enantiomerically pure 1,3-dioxanes has been found to proceed with moderate enantioselectivity.104 The homoallylic alcohol can be liberated by oxidation followed by base-catalyzed (3-elimination. The alcohols obtained in this way are formed in 70 5% e.e. 

The complex -Tol-BINAP-AgF (/>-Tol-BINAP - 2,2 -bis(di-/)-tolylphosphanyl)-l,l -binapthyl) catalyzes the asymmetric addition of allylic trimethoxysilanes to aldehydes (Equation (7)).7 3 The process can provide various optically active homoallylic alcohols with high enantioselectivity (up to 96% ee) and a remarkable 7 and anti- selectivities are observed for the reaction with crotylsilanes, irrespective of the configuration of the double bond ... 

Synthetic activity associated with the carbonyl-ene reaction is extensive. During the past decade, the trend has been to perform these reactions in the presence of a Lewis acid in an enantioselective fashion. Efforts to find a general catalyst that affords homoallylic alcohols in high yields and enantioselectivities are continual. The synthetic utility of this reaction has been validated by its application to the synthesis of a number of natural products (see Section 10.12.6) and many structurally novel motifs that have found a place in drug discovery vide infra). It is the latter application that has resulted in research efforts aimed at large-scale production of carbonyl-ene adducts. 

Enantioselective hydrogenation of unsaturated alcohols such as allylic and homoallylic alcohols was not very efficient until the discovery of the BINAP-Ru catalyst. With Ru(BINAP)(OAc)2 as the catalyst, geraniol and nerol are successfully hydrogenated to give (S)- or (R)-citronellol in near-quantitative yield and with 96-99% ee [3 c]. A substratexatalyst ratio (SCR) of up to 48 500 can be applied, and the other double bond at the C6 and C7 positions of the substrate is not reduced. A high hydrogen pressure is required to obtain high enantioselec-... 

Reactions of aldehydes with complexes 13—17 provide optically active homoallylic alcohols. The enantioselectivities proved to be modest for 13—16 (20—45% ee). In contrast, they are very high (> 94% ee) for the (ansa-bis(indenyl))(r]3-allyl)titanium complex 17 [32], irrespective of the aldehyde structure, but only for the major anti diastereomers, the syn diastereomers exhibiting a lower level of ee (13—46% ee). Complex 17 also gives high chiral induction (> 94% ee) in the reaction with C02 [32], in contrast to complex 12 (R = Me 11 % ee R = H 19% ee) [15]. Although the aforementioned studies of enan-... 

Ru(II)-BINAP complexes (1) can effect enantioselective hydrogenation of pro-chiral ally lie and homoallylic alcohols, without hydrogenation of other double bonds in the same substrate.1 The alcohols geraniol (2) and nerol (3) can be reduced to either (R)- or (S)-citronellol (4) by choice of either (R)- or (S)-l. Thus the stereochemical outcome depends on the geometry of the double bond and the chirality... 

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... 

The BINAP-Rh catalyzed hydrogenation of functionalized olefins has a mechanistic drawback as described in Section 1.2.1. This problem was solved by the exploitation of BINAP-Ru(ll) complexes.Ru(OCOCH3)2(binap) catalyzes highly enantioselective hydrogenation of a variety of olefinic substrates such as enamides, a, (3- and (3,y-unsaturated carboxylic acids, and allylic and homoallylic alcohols (Figure 1.9). " " Chiral citronellol is produced in 300 ton quantity in year by this reaction. ... 

Enantiomerically pure diisopropyl D-tartrate (d-DIPT) can be used effectively as a chiral poison for racemic BINOLato-Ti(0 Pr)2- catalyzed addition of allyltributyl-tin to aldehydes (Scheme 8.7). The enantioselectivity of the product increases with an increase in the amount of d-DIPT employed. When Ti(0 Pr)4 and d-DIPT are employed in the ratio of 1 3, the enantioselectivity and yield of the homoallylic alcohol product increase to 91 % ee and 63% from 19% ee and 44% in a ratio of 1 1. 

A symmetric activation is also observed in the combination of (/f)-BINOL and Zr(0 Bu)4, which promotes enantioselective synthesis of homoallylic alcohols (Scheme 8.13). A 2 1 ratio of (/ )-BINOL and Zr(0 Bu)4 without any other chiral source affords the homoallylic alcohol product in 27% ee and 44% yield. Addition of (7 )-(+)-a-methyl-2-naphthalenemethanol ((/ )-MNM) leads to higher enantiomeric excess (53% ee) than those using only (7 )-BINOL. Therefore, (7 )-MNM can act as a chiral activator a higher ee can be achieved via activation of the allylation of benzaldehyde by addition of (7 )-MNM as a product-like activator. 

The enantioselective addition of an allylsilane to an aldehyde catalyzed by chiral acyloxyborane (CAB) 13 is an excellent method for obtaining optically active homoallyl alcohols.Itsuno and Kumagai reported that the synthesis of a new optically active polymer with chirality on the mainchain is possible by applying this reaction to the asymmetric polymerization of bis(allylsilane) and dialdehyde (Scheme 12.11). ... 

In a recent paper, Zhang and Yamamoto have described a modified BHA ligand (235d) that is suitable for highly enantioselective vanadium-catalyzed epoxidation of homoallylic alcohols (Scheme 102). Both tram- and cA-substituted epoxides were achieved with nearly complete enantioselectivities and good yields. 

Allylic and homoallylic alcohols are particularly good substrates for epoxidation by TBHP/Vv and TBHP/ MoVI catalysts, with the former being superior in activity and selectivity (equations 70-72).57,226,242 Allylic alcohols have also been shown to be particularly good substrates for enantioselective epoxidation. Good results were observed in some cases with TBHP/VO(acac)2/chiral hydroxamates (equation 73),57 but a major breakthrough was obtained... 

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