BINAP unsaturated alcohols

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-... 

Homogeneous chiral hydrogenation of unsaturated alcohols, or carboxylic acids, enamides, ketones in the presence of a BINAP Ru or Rh complex as catalyst (see 1st edition). 

The slow-reacting 5 enantiomer is obtained in greater than 99% ee at 54% conversion. Hydrogenation of the partially resolved unsaturated Alcohol (80% ee) with the (5)-BINAP-containing catalyst, in turn, affords the enantiomeric 15,35 saturated alcohol in greater than 99% ee m 68% yield (overall 37%) and unreacted 5 alcohol in 40% ee in 32% yield. 

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... 

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]. 

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 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. ... 

Enantioselective isomerization can be advantageously used for the kinetic resolution of racemic allyl alcohols. For example treatment of 4-hydroxy-2-cyclopente-none (rac-28) in the presence of Rh[(R)-BINAP](MeOH)2 + gives rise to the enan-tiomerically enriched allyl alcohol (R)-29 (Scheme9) [13]. This unsaturated hydroxy ketone is an important building block for the synthesis of prostaglandins... 

Asymmetric catalysis undertook a quantum leap with the discovery of ruthenium and rhodium catalysts based on the atropisomeric bisphosphine, BINAP (3a). These catalysts have displayed remarkable versatility and enantioselectivity in the asymmetric reduction and isomerization of a,P- and y-keto esters functionalized ketones allylic alcohols and amines oc,P-unsaturated carboxylic acids and enamides. Asymmetric transformation with these catalysts has been extensively studied and reviewed.81315 3536 The key feature of BINAP is the rigidity of the ligand during coordination on a transition metal center, which is critical during enantiofacial selection of the substrate by the catalyst. Several industrial processes currently use these technologies, whereas a number of other opportunities show potential for scale up. 

This ligand, MeO-BIPHEP (96a), has shown similar reactivities and enantioselectivities to catalysts that contain BINAP.117 Ruthenium catalysts that contain MeO-BIPHEP have been used in several asymmetric hydrogenations from bench scale to multi-ton scale, which include the large-scale preparation of a P-keto ester, an aryl ketone, allylic alcohol, and several oc,P-unsaturated carboxylic acid substrates, which are shown in Figure 12.5. 

The analogous reaction of unsaturated lactones and lactams is strongly accelerated in the presence of alcohols which protonate the copper enolate formed in the conjugate reduction.281 This protocol was used in an enantioselective synthesis of the antidepressant (—)-paroxetine 324. Here, the key step was the conjugate reduction of the lactam 322 by PMHS in the presence of /-amylalcohol and catalytic amounts of CuCl2, ( S)- -tol-BINAP, and sodium /-butoxide, giving the product 323 with 90% yield and 90% ee (Scheme 90).281 The second chirality center was installed by diastereoselective alkylation of 323. 

Ru is more fussy about ligands (BINAP is the one usually if it is an allylic alcohol or an a, J-unsaturated carboxylic... 

The asymmetric transfer hydrogenation of the unsaturated carboxylic acids using formic acid or alcohols as the hydrogen source is catalyzed by Ru(acac-F6)( / -C3H5)(BINAP) or [RuH(BINAP)2]PFe to produce the saturated acids in up to 97% ee (eq 15). ... 

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. 

BINAP-ruthenium(II) is particularly good at catalysing the hydrogenation of allylic alcohols, and of a,P-unsaturated carboxylic acids to give acids bearing a stereogenic centres (like naproxen above). 

The hydrogenation of allylic alcohols and a,y9-unsaturated acids (type 18) is another class of transformations with a high industrial success rate. Again, some illustrative examples are Structures 28-33 preferred catalysts are Ru/BINAP... 

BINAP was first introduced by Noyori [80]. It has been particularly explored for reduction with ruthenium catalysts. BINAP is an atropisomeric ligand because rotation aroimd the central C-C bond is blocked. Accordingly BINAP exists in two enantiomers. Complexes of Ru(II) with BINAP are extremely powerful catalysts for enantioselective hydrogenations of prochiral a,p- and P,Y-unsaturated carboxylic acids, enamides, allylic and homoallylic alcohols, imines etc. [83]. In many cases, the hydrogenation is quantitative with enantiomeric excesses of over 95%. A wide variety of vitamins, terpenes, P-lactam antibiotics, etc. are accessible by the use of catalysts containing the BINAP stereogenic element. An example for 3-oxo carboxylic esters is shown in reaction (1) of Fig. 6.32. 

Two ruthenium complexes, binap 3.43-Ru(OCOR)2(R = Me,CF3) [892] and binap 3.43-RuX2 (X = Cl, Br, I) [893, 894], are quite useful. The acetate and trifluoroacetate complexes of 3.43 induce selective asymmetric hydrogenations of classes of prochiral olefins that are poorly selective with rhodium complexes. These classes include a,(3- or fcy-unsaturated acids and esters, ally alcohols, j3-acylaminoacrylates and enamide precursors of isoquinoline alkaloids [752, 853, 859, 881, 883, 895]. 

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