BINAP allylic alcohols

The great selectivity of Ru-BINAP species is also evident when they are used in kinetic resolution of enantiomers. When a racemic allylic alcohol reacts with H2 in the presence of Ru-(A)-BINAP, the (R)-alcohol reacts preferentially, thus leaving the (S)-enantiomer unreacted (Equation (7)).71... 

In parallel to the asymmetric catalytic isomerization of allylamines, [Rh(BINAP) (solvent)2]C104 is a very efficient catalyst for the isomerization of allylic alcohols.9,11 By employing 0.5mol% of the catalyst, good to excellent conversions were achieved even in the case of substrates that are more difficult to isomerize, such as allylic alcohols having two alkyl groups in the terminal position (R1 = R2 = Me) and 2-cyclohexen-l-ol (Scheme 19). 

Although the asymmetric isomerization of allylamines has been successfully accomplished by the use of a cationic rhodium(l)/BINAP complex, the corresponding reaction starting from allylic alcohols has had a limited success. In principle, the enantioselective isomerization of allylic alcohols to optically active aldehydes is more advantageous because of its high atom economy, which can eliminate the hydrolysis step of the corresponding enamines obtained by the isomerization of allylamines (Scheme 26). 

The enantioselective isomerization of allylic alcohols using cationic rhodium(l)/BINAP complex was reported.9,11 Although the enantioselectivities were lower than those achieved by the isomerization of the corresponding enamines, 3,3 -disubstituted allylic alcohols were isomerized to the corresponding aldehydes in moderate yield and enantioselectivity (Scheme 27). 

In the case of acyclic allylic alcohols, an efficient kinetic resolution of l-buten-3-ol was achieved using [Ru((7 )-BINAP)(H)(CH3CN)(THF)2]BF4 as catalyst (Equation (16)).55... 

Asymmetric cyclization was also successful in the rhodium-catalyzed hydrosilylation of silyl ethers 81 derived from allyl alcohols. High enantioselectivity (up to 97% ee) was observed in the reaction of silyl ethers containing a bulky group on the silicon atom in the presence of a rhodium-BINAP catalyst (Scheme 23).78 The cyclization products 82 were readily converted into 1,3-diols 83 by the oxidation. During studies on this asymmetric hydrosilylation, silylrhodation pathway in the catalytic cycle was demonstrated by a deuterium-labeling experiment.79... 

Complexes containing one binap ligand per ruthenium (Fig. 3.5) turned out to be remarkably effective for a wide range of chemical processes of industrial importance. During the 1980s, such complexes were shown to be very effective, not only for the asymmetric hydrogenation of dehydroamino adds [42] - which previously was rhodium s domain - but also of allylic alcohols [77], unsaturated acids [78], cyclic enamides [79], and functionalized ketones [80, 81] - domains where rhodium complexes were not as effective. Table 3.2 (entries 3-5) lists impressive TOF values and excellent ee-values for the products of such reactions. The catalysts were rapidly put to use in industry to prepare, for example, the perfume additive citronellol from geraniol (Table 3.2, entry 5) and alkaloids from cyclic enamides. These developments have been reviewed by Noyori and Takaya [82, 83]. 

With an increase of conversion, the enantiopurity of unreacted (S)-substrate increases and the diastereoselectivity of the product decreases. Using Ru-((S)-binap)(OAc)2, unreacted (S)-substrate was obtained in more than 99% ee and a 49 1 mixture of anti-product (37% ee (2R,iR)) at 76% conversion with a higher kR ks ratio of 16 1 [46]. In the case of a racemic cyclic allyl alcohol 24, high enantiopurity of the unreacted alcohol was obtained using Ru-binap catalyst with a high kR ks ratio of more than 70 1 [Eq. (16)] [46]. In these two cases, the transition state structure is considered to be different since the sense of dia-stereoface selection with the (S)- or the (R)-catalysts is opposite if a similar OH/ C=C bond spatial relationship is assumed. 

BINAP (40a) was first reported as a ligand in an enantioselective hydrogenation in 1980 [172], and provides good selectivity for the reductions of dehydroamino acid derivatives [173], enamides, allylic alcohols and amines, and a,p-unsaturated acids [4, 9, 11, 12, 174, 175]. The fame of the ligand system really came with the reduction of carbonyl groups with ruthenium as the metal [11, 176]. The Rh-BINAP systems is best known for the enantioselective isomerizations... 

The hydrogenation of allylic alcohols and a,/>-unsaluraled acids leads to products with a very high synthetic potential, and both transformations were used quite early for industrial applications. In both cases Ru complexes with axially chiral biaryl ligands (binap analogues) are the catalysts of choice. Here, we will dis-... 

Many methods have been reported for the enantioselective synthesis of the remaining PG building block, the (J )-4-hydroxy-cyclopent-2-enone. For example, the racemate can be kinetically resolved as shown in Scheme 7-28. (iS )-BINAP-Ru(II) dicarboxylate complex 93 is an excellent catalyst for the enantioselective kinetic resolution of the racemic hydroxy enone (an allylic alcohol). By controlling the reaction conditions, the C C double bond in one enantiomer, the (S )-isomer, will be prone to hydrogenation, leaving the slow reacting enantiomer intact and thus accomplishing the kinetic resolution.20... 

Similarly,110 (lR,2S )-ephedrine is an effective poison in the kinetic resolution of allylic alcohols using racemic BINAP instead of the expensive (R)-BINAP. (/ )-2-cycIohexenoI can thus be obtained in >95% ee using a racemic... 

Kinetic resolution ofallylic alcohols. The (R)- and (S)-BINAP-Ru diacetate complexes can resolve racemic allylic alcohols, both acyclic and cyclic, with high enantiomeric selectivity. Thus hydrogenation of ( )-2 catalyzed by (S)-l at 76% conversion provides (S)-2 (>99% ee) and anti-3 (49 1, 39% ee). Hydrogenation of (S)-2 catalyzed by either (R)- or (S)-l provides anti-3 (>23 1). Similar results obtain with ( )-4. 

ASYMMETRIC HYDROGENATION OF ALLYLIC ALCOHOLS USING BINAP-RUTHENIUM COMPLEXES (S)-(-)-CITRONELLOL (6-Octen-1-ol, 3,7-dimethyl, (S)-)... 

For Rh(I)/BINAP-catalyzed isomerizations of allylic amines, the mechanistic scheme outlined in Eq. (2) has been proposed. The available data are consistent with the notion that Rh(I)/PF-P(o-Tol)2-catalyzed isomerizations of allylic alcohols follow a related pathway [11]. For example, the only deuterium-containing product of the reaction depicted in Eq. (9) is the l,3-dideuterated aldehyde, which estabhshes that the isomerization involves a clean intramolecular 1,3-migration. The data illustrated in Eqs. (10) and (11) reveal that the catalyst selectively abstracts one of the enantiotopic hydrogens/ deuteriums alpha to the hydroxyl group. 

One of the landmark achievements in the area of enantioselective catalysis has been the development of a large-scale commercial application of the Rh(I)/BINAP-catalyzed asymmetric isomerization of allylic amines to enamines. Unfortunately, methods for the isomerization of other families of olefins have not yet reached a comparable level of sophistication. However, since the early 1990s promising catalyst systems have been described for enantioselective isomerizations of allylic alcohols and aUylic ethers. In view of the utility of catalytic asymmetric olefin isomerization reactions, I have no doubt that the coming years will witness additional exciting progress in the development of highly effective catalysts for these and related substrates. 

Substituted acrylates (which reseitible the enamide substrates employed 1n asymmetric hydrogenation) may be deracemized by reduction with an optically active catalyst, especially DIPAMPRh . Selectivity ratios of 12 1 to 22 1 have been obtained for a variety of reactants with compounds of reasonable volatility, separation of starting material and product may be effected by preparative GLC. Recovered starting material can then be reduced with an achiral catalyst to give the optically pure anti product. Examples of kinetic resolutions by this method are given in Table II. More recently very successful kinetic resolutions of allylic alcohols have been carried out with Ru(BINAP) catalysts. 

SCHEME 32. Kinetic resolution of allylic alcohols by BINAP -Ru-catalyzed hydrogenation. 

When racemic 3-methyl-2-cyclohexenol is hydrogenated by the BINAP-Ru catalyst at 4 atm H2, trcms- and cis-3-methylcyclohexanol are produced in a 300 1 ratio (Scheme 33). The reaction with the (/ )-BINAP complex affords the saturated R,3R trans alcohol in 95% ee in 46% yield and unreacted S allylic alcohol in 80% ee with 54% recovery. 

Scheme 21). Scheme 22 illustrates an example of kinetic resolution of a racemic allylic alcohol with a 1,3-hydrogen shift. When racemic 4-hydroxy-2-cyclopentenone is exposed to a cationic (/ )-BINAP-Rh complex in THF, the S enantiomer is consumed five times faster than the R isomer (32). The slow-reacting stereoisomer purified as the crystalline ferf-butyldimethylsilyl ether is an intermediate in prostaglandin synthesis (33). These isomerizations may occur via initial Rh-olefinic bond interaction (34). 

Benzamido-cinnamic acid, 20, 38, 353 Benzofuran polymerization, 181 Benzoin condensation, 326 Benzomorphans, 37 Benzycinchoninium bromide, 334 Benzycinchoninium chloride, 334, 338 Bifiinctional catalysts, 328 Bifiinctional ketones, enantioselectivity, 66 BINAP allylation, 194 allylic alcohols, 46 axial chirality, 18 complex catalysts, 47 cyclic substrates, 115, 117 double hydrogenation, 72 Heck reaction, 191 hydrogen incorporation, 51 hydrogen shift, 100 hydrogenation, 18, 28, 57, 309 hydrosilylation, 126 inclusion complexes, oxides, 97 ligands, 19, 105 molecular structure, 50, 115 mono- and bis-complexes, 106 NMR spectra, 105 olefin isomerization, 96... 

SCH EME 29. Asymmetric hydrogenation of allylic alcohols catalyzed by Ru(OCOCH3)2-[(S)-binap] in methanol at 4 and 100 atm. 

In the presence of a cationic Rh[((/ )-binap)(cod)] complex, geranyl or neryl amides isomerize slowly to give a mixture of the corresponding enamide and dienamide (Scheme 20) (2). The optical purity of the chiral enamide is high, but the chemical yield is low. Certain cyclic allylic amides give the enamide isomers in a high ee. With a DIOP-Rh catalyst, prochiral allylic alcohols are converted to optically active aldehydes with low ee (31). 

A cationic BINAP-Rh complex catalyzes asymmetric isomerization of some allylic alcohols in THF to give chiral aldehydes in moderate ee... 

Allylic andHomoaltylic Alcohols In spite of many examples of diastereoselective hydrogenation of chiral allylic alcohols by using achiral Rh or Ir complexes [134], the enantioselective versions were unsuccessful, With a neutral Cy-BINAP-Rh complex, geraniol or nerol is hydrogenated in benzene to produce citronellol with only 50-60% ee [135]. The use of cationic BINAP-Rh complexes markedly reduces the enantioselectivity. 

In the BINAP-Ru-catalyzed hydrogenation of 2-substituted 2-propen-1-ols, only a low level of enantioselectivity is observed. The selectivity is, however, pronouncedly enhanced by use of 2,4,6-trichlorobenzoate of the original allylic alcohol (Scheme 1.25) [140],... 

Recently it has been reported that the catalytic isomerization of allylic alcohols is promoted by [Rh(diphosphine)(solvent)2]+ at 25°C yields synthetically useful quantities of the corresponding simple enols and that the transformation of allylic alcohols to enols and thereby to ketonic products proceeds catalytically via hydrido-7t-allylic and hydrido-7t-oxy-allylic intermediates, respectively [20]. Consistently observed, enantioselection has been in the process of conversion of a prochiral enol to a chiral aldehyde. Thus, the prochiral substrate 32 is transformed to the optically active aldehyde 34 with 18% ee by using [Rh(BINAP)]+ catalyst (eq 3.13). Accordingly, this isomerization proceeds via a different mechanism from that of the isomerization of allylamine. For the reaction mechanism of the... 

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