Homoallylic alcohols oxidation

Allyllic ether 53 is oxidized regioselectively to the /3-alkoxy ketone 54, which is converted into the a,/i-unsaturated ketone 55 and used for annulation[99]. The ester of homoallylic alcohol 56 is oxidized mainlv to the 7-acetoxy ketone 57[99]. 

The 4-hydroxy-1-alkene (homoallylic alcohol) 81 is oxidized to the hetni-acetal 82 of the aldehyde by the participation of the OH group when there is a substituent at C3. In the absence of the substituent, a ketone is obtained. The hemiacetal is converted into butyrolactone 83[117], When Pd nitro complex is used as a catalyst in /-BuOH under oxygen, acetals are obtained from homoallylic alcohols even in the absence of a substituent at C-3[l 18], /-Allylamine is oxidized to the acetal 84 of the aldehyde selectively by participation of the amino group[l 19],... 

These are usually obtained from the isomeric conjugated ketone, and are sometimes useful as intermediates, offering an alternative to enol derivatives. They may also be formed as a result of double bond introduction or by oxidation of homoallylic alcohols if so the conditions must be mild because they generally represent a less stable isomer. 

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. 

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. 

Several strategies have been proposed to improve the regioselectivity of nitrile oxide cycloaddition. Kanemasa and coworkers have reported high-rate acceleration and regioselectivity in nitrile oxide cycloadditions to the magnesium alkoxides of allylic and homoallylic alcohols (Eq. 8.64)."... 

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). 

With the aid of BF3 OEt2, methoxyborolane (R,R)-114 reacts with (.E)- or (Z)-crotylpotassium to provide (is,R,R)-115 and (Z,R,R)-115, respectively. After adding the aldehyde to a solution of crotyl-borolane in THF at —78°C for 4 hours, 2-aminoethanol is added. The solution is warmed to room temperature, and oxidative cleavage at this point gives the homoallylic alcohols with high stereoselectivity. The borolane moiety can be recovered by precipitating it as an amino alcohol complex and can be reused without any loss of enantiomeric purity. As shown in Scheme 3-43, the (.E)- and (Z)-crotyl compounds lead to anti- and -products 116, respectively. The diastereoselectivity is about 20 1, and the ee for most cases is over 95% (Table 3-11). 

Figure 5.3 Oxidation of some (Z)-allylic alcohols and some homoallylic alcohols using poly(tartrate).

Intramolecular hydrosilylation.1 Hydrosilylation of internal double bonds requires drastic conditions and results in concomitant isomerization to the terminal position. However, an intramolecular hydrosilylation is possible with allylic or homoallylic alcohols under mild conditions by reaction with 1 at 25° to give a hydrosilyl ether (a), which then forms a cyclic ether (2) in the presence of H2PtCl6-6H20 at 60°. Oxidative cleavage of the C—Si bond results in a 1,3-diol (3). 

Intramolecular hydrosilation. Tamao et al. have extended their hydrosily-lation-oxidation sequence (12,243-245) to allyl and homoallyl alcohols as an approach to 1,3-diols. When applied to cyclic homoallylic alcohols, only a cis-1,3-diol is obtained, presumably by way of a cyclic intermediate (equation I). Acyclic homoallylic alcohols can be converted by this approach to either syn- or anti-1,3-... 

The mechanism of the Zn chloride-assisted, palladium-catalyzed reaction of allyl acetate (456) with carbonyl compounds (457) has been proposed [434]. The reaction involves electroreduction of a Pd(II) complex to a Pd(0) complex, oxidative addition of the allyl acetate to the Pd(0) complex, and Zn(II)/Pd(II) transmetallation leading to an allylzinc reagent, which would react with (457) to give homoallyl alcohols (458) and (459) (Scheme 157). Substituted -lactones are electrosynthesized by the Reformatsky reaction of ketones and ethyl a-bromobutyrate, using a sacrificial Zn anode in 35 92% yield [542]. The effect of cathode materials involving Zn, C, Pt, Ni, and so on, has been investigated for the electrochemical allylation of acetone [543]. 

The oxidation of alcohols to carbonyl compounds has been studied by several authors and a variety of methods have been used. Papers concerned vith such oxidations are illustrated (Scheme 3.26). Good results have been obtained using pyridinium chlor-ochromate (PCC) adsorbed onto silica gel for the selective oxidation of unsaturated substrates e.g. terpene [135] and furanyl derivatives [136]. Steroidal homoallylic alcohols can be converted to the corresponding 4-ene-3,6-diones using tetrapropylammo-nium per-ruthenate (TPAP) in catalytic amounts [137]. In this case, the oxidising agent is N-methyl morpholine N-oxide (NMO). 

Our collective mechanistic studies are consistent with the indicated catalytic cycle. Notably, the catalyst engages primary alcohols in rapid and reversible dehydrogenation, yet the coupling products, which are homoallylic alcohols, are not subject to oxidation as coordination of the homoallylic olefin to the catalyst provides a hexa-coordinate 18-electron complex lacking an open coordination site for p-hydride elimination (Scheme 14). 

As demonstrated in recent work by Obora and Ishii, alkynes serve as allyl donors in carbonyl allylations from the alcohol oxidation level [277]. Specifically, upon exposure to an iridium catalyst generated in situ from [lr(OH)(cod)]2 and P( -Oct)3, l-aryl-2-methylalkynes couple to primary alcohols to furnish homoallylic alcohols with complete branched regioselectivity and excellent levels of diastereoselectivity (Scheme 17). 

The BINAP derivative of the ort/io-cyclometallated iridium catalyst has been characterized by single crystal X-ray diffraction analysis [280]. Remarkably, although the reaction sequence depends upon oxidation of either the reactant alcohol or isopropanol, the enantiomeric purity of the homoallylic alcohol product... 

Allylic and homoallylic alcohols are particularly susceptible to oxidation and dehydration. Hiskey and Oxley successfully nitrated both allyl alcohol and l-buten-4-ol with nitronium tetrafluoroborate in diethyl ether at -71 °C. 

Allyltin difluoroiodide, formed in situ by the oxidative addition of stannous fluoride to allyl iodide, is found to react with carbonyl compounds to give the corresponding homoallylic alcohols in excellent yields under mild reaction conditions (9). 

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. 

Reaction of styrene oxide with tetraallyltin in the presence of Bi(OTf)3 (2 mol%) affords the corresponding l-phenyl-4-penten-2-ol (Fig. 5). In a similar fashion, various aryl substituted epoxides react smoothly with tetraallyltin to give the corresponding homoallylic alcohols. This method give generality as cycloalkyl oxiranes and sterically hindered ones give the corresponding homoallylic alcohols. 

Zrrconium(IV) and hafnium(IV) complexes have also been employed as catalysts for the epoxidation of olefins. The general trend is that with TBHP as oxidant, lower yields of the epoxides are obtained compared to titanium(IV) catalyst and therefore these catalysts will not be discussed iu detail. For example, zirconium(IV) alkoxide catalyzes the epoxidation of cyclohexene with TBHP yielding less than 10% of cyclohexene oxide but 60% of (fert-butylperoxo)cyclohexene °. The zirconium and hafnium alkoxides iu combiuatiou with dicyclohexyltartramide and TBHP have been reported by Yamaguchi and coworkers to catalyze the asymmetric epoxidation of homoallylic alcohols . The most active one was the zirconium catalyst (equation 43), giving the corresponding epoxides in yields of 4-38% and enantiomeric excesses of <5-77%. This catalyst showed the same sense of asymmetric induction as titanium. Also, polymer-attached zirconocene and hafnocene chlorides (polymer-Cp2MCl2, polymer-CpMCls M = Zr, Hf) have been developed and investigated for their catalytic activity in the epoxidation of cyclohexene with TBHP as oxidant, which turned out to be lower than that of the immobilized titanocene chlorides . ... 

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