Homoallylic alcohols hydrogenation

Regioselective Hydrogenation- allylic and homoallylic alcohols are hydrogenated faster than isolated double bonds... 

Isopinocampheyl(l-isopinocampheyl-2-octenyl)borinic acid (1), available with a diastereomer-ic purity of approximately 80 85% de, reacts smoothly with aldehydes at —15 °C in tetrahy-drofuran to provide a homoallylic alcohol with 79-85% ee after oxidative workup (30% hydrogen peroxide, 40 °C)6. 

Iridium-catalyzed transfer hydrogenation of aldehyde 73 in the presence of 1,1-dimethylallene promotes tert-prenylation [64] to form the secondary neopentyl alcohol 74. In this process, isopropanol serves as the hydrogen donor, and the isolated iridium complex prepared from [Ir(cod)Cl]2, allyl acetate, m-nitrobenzoic acid, and (S)-SEGPHOS is used as catalyst. Complete levels of catalyst-directed diastereoselectivity are observed. Exposure of neopentyl alcohol 74 to acetic anhydride followed by ozonolysis provides p-acetoxy aldehyde 75. Reductive coupling of aldehyde 75 with allyl acetate under transfer hydrogenation conditions results in the formation of homoallylic alcohol 76. As the stereochemistry of this addition is irrelevant, an achiral iridium complex derived from [Ir(cod)Cl]2, allyl acetate, m-nitrobenzoic acid, and BIPHEP was employed as catalyst (Scheme 5.9). 

Synthetic transformations of the products of the intramolecular bis-silylation have been examined. The five-membered ring products derived from homopropargylic alcohols were hydrogenated in a stereoselective manner (Scheme ll).90 Oxidation of the products under the Tamao oxidation conditions (H202/F /base)96 leads to the stereoselective synthesis of 1,2,4-triols. This method can be complementary to the one involving intramolecular bis-silylation of homoallylic alcohols (vide infra). 

The hydrogenation of acyclic homoallylic alcohols with a 1,1-disubstituted ole-fmic bond by cationic [Rh(diphos-4)]+ catalyst proceeds in modest to moderate stereoselectivity, generally forming 1,3-anti compounds (Table 21.10, entries 1, 4 and 5), and the effect of the stereogenic center at the allylic position overrides the directivity of hydroxyl group. The 1,3-syn product is then observed though in poor selectivity (entry 3) [19, 57, 58]. Inspection of the hydrogenation prod-... 

In the case of tri-substituted alkenes, the 1,3-syn products are formed in moderate to high diastereoselectivities (Table 21.10, entries 6—12). The stereochemistry of hydrogenation of homoallylic alcohols with a trisubstituted olefin unit is governed by the stereochemistry of the homoallylic hydroxy group, the stereogenic center at the allyl position, and the geometry of the double bond (Scheme 21.4). In entries 8 to 10 of Table 21.10, the product of 1,3-syn structure is formed in more than 90% d.e. with a cationic rhodium catalyst. The stereochemistry of the products in entries 10 to 12 shows that it is the stereogenic center at the allylic position which dictates the sense of asymmetric induction... 

Table 21.10 Hydroxy-directed hydrogenation of acyclic homoallyl 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-... 

The hydrogenation of a racemic homoallylic alcohol is the key reaction for a new synthetic route for producing paroxetine, and recently reported by Ricordati [68] (Fig. 37.14). The best results (>99% ee for both cis and trans products) were... 

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 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. ... 

The addition of allylic boron reagents to carbonyl compounds first leads to homoallylic alcohol derivatives 36 or 37 that contain a covalent B-O bond (Eqs. 46 and 47). These adducts must be cleaved at the end of the reaction to isolate the free alcohol product from the reaction mixture. To cleave the covalent B-0 bond in these intermediates, a hydrolytic or oxidative work-up is required. For additions of allylic boranes, an oxidative work-up of the borinic ester intermediate 36 (R = alkyl) with basic hydrogen peroxide is preferred. For additions of allylic boronate derivatives, a simpler hydrolysis (acidic or basic) or triethanolamine exchange is generally performed as a means to cleave the borate intermediate 37 (Y = O-alkyl). The facility with which the borate ester is hydrolyzed depends primarily on the size of the substituents, but this operation is usually straightforward. For sensitive carbonyl substrates, the choice of allylic derivative, borane or boronate, may thus be dictated by the particular work-up conditions required. 

Nickel-containing polyfluorometalated [Ni(H20)H2FeNaWi7055] was capable of catalytic activation of hydrogen peroxide for allylic alcohol oxidation in biphasic conditions (catalyst substrate ratio 1 1000). Homoallylic alcohols are significantly less reactive than allylic homologues and cis > trans reactivity is found also in this case. 

The structure of the sulfonimidoyl-substituted homoallyl alcohols 4-7 in solution and in the crystal is characterized by an intramoleculare hydrogen bond between the OH group and the N atom of the sulfonimidoyl group. 

Methanol promotes addition of allylstannanes to aldehydes and ketones, to give homoallylic alcohols without added catalyst.86 Aldehydes are significantly more reactive. It is suggested that the primary activating influence is hydrogen bonding to the carbonyl. 

Looking first at alcohol-directed reductions62, it is apparent that there have been many studies of the reduction of allylic and homoallylic alcohols using both the neutral and cationic reduction complexes based on rhodium, iridium etc. In the case of cyclic substrates where an alcohol is located on one side of a ring, the hydrogen is simply delivered cis to the alcohol function63. This is illustrated by key reduction steps in the synthesis of monensin (Scheme 5)64 and the marine natural product arenarol (Scheme 6)65. In each... 

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