Cyclohexenol, allylic

Stork and Kahne 108) have demonstrated remarkable stereochemical control in the hydrogenation of a series of cyclohexenols containing allylic... 

In a new version of the Simmons-Smith reaction allyl or aUenic alcohols such as cyclohexenol are converted by Sm/CH2l2/Me3SiCl 14 in THF at -78°C into syn cyclopropanols such as 2135 [63] (Scheme 13.17). 

A novel procedure for the synthesis of an indole skeleton 81 was developed by Mori s group (Scheme 13).16e,16f Enantioselective allylic amination of 78 with A-sulfonated < r/ < -bromoaniline 79 followed by Heck cyclization of 80 provided chiral indoline 81. The treatment of a cyclohexenol derivative 78 with 79 in the presence of Pd2(dba)3-GHGl3 and ( )-BINAPO gave compound 80 with 84% ee in 75% yield. Total syntheses of (—)-tubifoline, (—)-dehydrotubifoline, and (—)-strychnine were achieved from compound 80. 

Ru complex and (CH3)3COK [(S, R)-34B] is also an excellent catalyst for hydrogenation of the cyclic enone [111]. The allylic alcohol product is a useful intermediate for the synthesis of carotenoid-derived odorants and other bioactive ter-penes. Hydrogenation of 2-cyclohexenone in the presence of the (S,S)-DIOP-Ir catalyst gives (R)-2-cyclohexenol in 25% ee (Fig. 32.43) [137]. 

Using methods developed by Sharpless (68), Reich (69), and others, the optically active 4,4-dimethyl-2-cyclohexenol is prepared in excellent yield from the corresponding chiral selenide (eq. [19]). The (S)-4,4-dimethyl-3-p-methylphenylselenocyclohexanone, [a] 42.1° (e.e. 39%), was reduced with sodium borohydride to the (one) diastereomeric alcohol, [a] 11.0°, in quantitative yield and converted to the allylic alcohol, [a] — 17.7°, with an e.e. of 40%. 

Cyclic allylic alcohols have different steric requirements than the acyclic substrates discussed above. Sarzi-Amade and coworkers addressed the mechanism of epoxida-tion of 2-cyclohexen-l-ol by locating all the transition structures (TSs) for the reaction of peroxyformic acid (PFA) with both pseudoequatorial and pseudoaxial cyclohexenol con-formers. Geometry optimizations were performed at the B3LYP/6-31G level, and the total energies were refined with single-point B3LYP/6-311- -G //B3LYP/6-31G calculations. 

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. 

Considering only the three mild oxidation products in the liquid phase, it can be inferred that the photocatalytic oxidation of cyclohexene occurs at two sites of the molecule mainly the allylic position (86 %), giving the cyclohexenone and the cyclohexenol, and, to much lesser extent, the double bond (14 %) yielding the epoxide. 

Hydrogenation of 2,4,4-trimethyl-2-cyclohexenone with rrans-RuCl2(tolbinap)(dpen) and (CH3)3COK under 8 atm of hydrogen gives 2,4,4-trimethyl-2-cyclohexenol quantitatively with 96% ee (Scheme 1.70) [256,275,276]. In this case, unlike in the reaction of aromatic ketones, the combination of the R diphosphine and S,S diamine most effectively discriminates the enantiofaces. The chiral allylic alcohol is a versatile intermediate in the synthesis of carotenoid-derived odorants and other bioactive terpens such as a-damascone and dihydroactinidiolide [277]. 

Montgomery and co-workers [36, 42] have shown that organozincs can also couple with alkynes and aldehydes via organonickel intermediates 26 with high degrees of chemo- and stereoselectivities to afford allylic alcohols 27 (Scheme 8.9). Recently, they reported a two-step, four-component synthesis of cyclohexenol de-... 

It is well known that in many brominations and protonations of cyclohexenols (91) axial entry is favored (Eliel et al., 1965). This is attributed to the parallel alignment of the v orbitals on the three centers. The overlap preference is well illustrated in the oxidation of allyl vs. saturated alcohols. Normally, axial alcohols are oxidized more rapidly by chromic acid than equatorial alcohols. In the absence of large strain factors, equatorial allyl alcohols are oxidized faster than axial alcohols by chromic acid hydrogen is abstracted in the rate-determining step. The contribution of a-j8 ketonic resonance lowers the activation energy,... 

Cyclopropropylmethyl radicals.1 Generation of a radical center adjacent to a cyclopropane can result in ring opening of the cyclopropylmethyl system. This reaction can be used to convert allylic cyclohexenols to alkylcyclohexenes, as shown for conversion of 1 into 3 via the phenyl selenide 2. When the cyclopropyl ring is... 

Recently two heterogeneous TPAP catalysts were developed which could be recycled successfully and displayed no leaching In the first example the tetraalkylammonium perruthenate was tethered to the internal surface of mesoporous silica (MCM-41) and was shown [ 101] to catalyse the selective aerobic oxidation of primary and secondary allylic and benzylic alcohols (Fig. 17). Surprisingly, both cyclohexanol and cyclohexenol were unreactive although these substrates can easily be accommodated in the pores of MCM-41. No mechanistic interpretation for this surprising observation was offered by the authors. 

An unusual syn addition to epoxides occurs when 1,3-diene monoepoxides are treated with organozinc reagents. Thus, the cyclic vinyl epoxide 72 was converted to the cis-ethyl-cyclohexenol 75 with diethyl zinc in methylene chloride and trifluoroacetic acid. The syn addition is believed to derive from an initial coordination of the oxiranyl oxygen to the organozinc compound, which then delivers the alkyl group to the same face. This transfer is facilitated by a relaxation of the sp3 hybridization brought about by the Lewis acidic zinc center and the allylic character of the incipient carbocation <020L905>. 

Overman et al. exercised the CBS reduction strategy during synthesis of the natural opium alkaloid (—)-morphine (50)21 (Scheme 4.3q). Enantioselective reduction of 2-allylcyclohex-2-en-l-one (51) with catecholborane in the presence of the (R)-oxazaborolidinc catalyst (l )-28a provided the corresponding (S)-cyclohexenol 52 in greater than 96% ee. Condensation of this intermediate with phenyl isocyanate, regioselective catalytic dihydroxylation of the terminal double bond, and protection of the resulting diol afforded 53 in 68% overall yield from 51. The ally lie silane 54 for the upcoming iminium ion-ally lsilane cycliza-tion step was obtained in 81% yield by a stereoselective Sn2 displacement of allylic carbamate. 

Treatment of cyclohexenol with HBr gives the corresponding allylic bromide. Only one compound is formed because attack at either end of the allylic cation gives the same product. 

With one exception—when the substituent is a hydroxyl group. When an allylic alcohol is epoxidized, the peroxy-acid attacks the face of the alkene syn to the hydroxyl group, even when that face is more crowded. For cyclohexenol the ratio of syn epoxide to anti epoxide is 24 1 with m-CPBA and it rises to 50 1 with CF3CO3H. 

Lithium amide deprotonation of epoxides is a convenient method for the preparation of allylic alcohols. Since the first deprotonation of an epoxide by a lithium amide performed by Cope and coworkers in 19585, this area has received much attention. The first asymmetric deprotonation was demonstrated by Whitesell and Felman in 19806. They enantioselectively rearranged me.vo-cpoxidcs to allylic alcohols for example, cyclohexene oxide 1 was reacted with chiral bases, e.g. (S,S) 3, in refluxing TFIF to yield optically active (/ )-2-cyclohexenol ((/ )-2) in 36% ee (Scheme 1). 

Stereoselective hydrogenation. A suitably placed hydroxyl group can exert control over the hydrogenation catalyzed by 1 of various cyclohexenols with allylic or homoallylic double bonds. 

Examples of the use of chromium(VI) reagents to effect the allylic oxidation of alkenes to give a,3-unsaturated carbonyl compounds are very common in the literature. The reaction was first reported by Treibs and Schmidt for the allylic oxidations of a-pinene to verbenone and verbenol, of dipentene to carvone and caiveol, and of cyclohexene to cyclohexenol and cyclohexenone, using a solution of chromium trioxide in a mixture of acetic anhydride and carbon tetrachloride. However, yields were low and no synthetic use of this observation was made. 

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