Cyclohexene, hydroxylation

Table III. Isotope Effects for Cyclohexene Hydroxylation by Cytochrome P 450LM2...

Chiral Alcohols and Lactones. HLAT) has been widely used for stereoselective oxidations of a variety of prochiral diols to lactones on a preparative scale. In most cases pro-(3) hydroxyl is oxidized irrespective of the substituents. The method is apphcable among others to tit-1,2-bis(hydroxymethyl) derivatives of cyclopropane, cyclobutane, cyclohexane, and cyclohexene. Resulting y-lactones are isolated in 68—90% yields and of 100% (164,165). 

C. Hydroxylation of Cyclohexene with Hydrogen Peroxide-Formic Acid 8, 9)... 

The synthesis of the trisubstituted cyclohexane sector 160 commences with the preparation of optically active (/ )-2-cyclohexen-l-ol (199) (see Scheme 49). To accomplish this objective, the decision was made to utilize the powerful catalytic asymmetric reduction process developed by Corey and his colleagues at Harvard.83 Treatment of 2-bromocyclohexenone (196) with BH3 SMe2 in the presence of 5 mol % of oxazaborolidine 197 provides enantiomeri-cally enriched allylic alcohol 198 (99% yield, 96% ee). Reductive cleavage of the C-Br bond in 198 with lithium metal in terf-butyl alcohol and THF then provides optically active (/ )-2-cyclo-hexen-l-ol (199). When the latter substance is treated with wCPBA, a hydroxyl-directed Henbest epoxidation84 takes place to give an epoxy alcohol which can subsequently be protected in the form of a benzyl ether (see 175) under standard conditions. 

The preparation of Pans-1,2-cyclohexanediol by oxidation of cyclohexene with peroxyformic acid and subsequent hydrolysis of the diol monoformate has been described, and other methods for the preparation of both cis- and trans-l,2-cyclohexanediols were cited. Subsequently the trans diol has been prepared by oxidation of cyclohexene with various peroxy acids, with hydrogen peroxide and selenium dioxide, and with iodine and silver acetate by the Prevost reaction. Alternative methods for preparing the trans isomer are hydroboration of various enol derivatives of cyclohexanone and reduction of Pans-2-cyclohexen-l-ol epoxide with lithium aluminum hydride. cis-1,2-Cyclohexanediol has been prepared by cis hydroxylation of cyclohexene with various reagents or catalysts derived from osmium tetroxide, by solvolysis of Pans-2-halocyclohexanol esters in a manner similar to the Woodward-Prevost reaction, by reduction of cis-2-cyclohexen-l-ol epoxide with lithium aluminum hydride, and by oxymercuration of 2-cyclohexen-l-ol with mercury(II) trifluoro-acetate in the presence of ehloral and subsequent reduction. ... 

When 35 was heated in acetic acid containing hydrogen bromide, the tribromide 46 was obtained as a single product in 74% yield. Debromina-tion of 46 with zinc dust in acetic acid furnished the cyclohexene derivative 47, which was converted into compound 48 by osmium tetraoxide hydroxyl-ation and acetylation. The substitution reaction of 48 with acetate ions provided carba-a-DL-glucopyranose pentaacetate (49), which gave the carba-sugar 50 on hydrolysis. ... 

The anti-Markovnikov product was formed with >95% regioselectivity at 35°C. The examples in Scheme 5-21, Eq. (1) show that cyano and hydroxyl functional groups are tolerated by the catalyst, and diphenylphosphine oxide can be added to both C=C bonds in a di-alkyne. The reaction also worked for internal alkynes (Scheme 5-21, Eq. 2). Unusual Markovnikov selectivity was observed, however, for 1-ethynyl-cyclohexene (Scheme 5-21, Eq. 3) [17]. 

Allylic rearrangements with 3,3,6,6-dj-cyclohexene occurred in 20% of the MMO hydroxylation products compared to 33% for cytochrome P-450. These two experiments suggest that, with M. trichospor-ium OB3b, a rebound reaction must occur with a greater rate constant than with cytochrome P-450, in accord with the radical clock substrate work. 

Rogers, J.D. (1989) Rate constant measurements for the reaction of the hydroxyl radical with cyclohexene, cyclopentene, and glutaraldehyde. Environ. Sci. Technol. 23, 177-181. 

OH radicals react very fast (almost in a diffusion-controlled rate) with simple alkenes (k = 7.0 x 109 for 1-butene or cyclopentene and 8.8 x 109 M 1 s 1 for cyclohexene) and there is almost no change for 1,3- or 1,4-cyclohexadiene. Cycloheptatriene reacts very fast with all the three radicals formed in the radiolysis of water k = 6 x 109 with eaq, 8 x 109 with H atoms and 1 x 101CI M 1 s 1 with hydroxyl radicals13. 

A study of the catalytic oxidation of six stereoisomers of 5-cyclohexene-l,2,3,4-tetrol revealed448 that, in all cases, an allylic hydroxyl group is selectively attacked, and a consideration of their favored conformations suggested that quasi-axial groups are selectively dehydrogenated before those that are quasi-equatorial. 

The first reactions concerned (Simons and Archer, 27) alkylation of benzene with propylene to form isopropylbenzene, with isobutene to form f-butylbenzene and di-f-butylbenzene, and trimethylethylene to form amylbenzene. Later on (Simons and Archer, 28) studied these and other reactions in more detail and showed that high yields could be obtained and that the product was not contaminated with tars or other obnoxious impurities. It was shown that the products obtained with trimethylethylene were mono- and di-f-amylbenzene, that phenyl-pentane resulted from the use of pentene-2, and that cyclohexene produced cyclohexylbenzene. Cinnamic acid reacted with benzene (Simons and Archer, 29) to form /3-phenylpropionic acid and allyl benzene reacted with benzene to form 1,2-diphenylpropane. It is interesting to note that although allyl alcohol reacted with benzene to form 1,2-diphenylpropane, the intermediate in the reaction, allylbenzene, was isolated and identified. This shows that in this case the hydroxyl reacted at a more rapid rate than the double bond. Both di- and triisobutylene reacted with phenol (Simons and Archer, 30) at 0°, when using hydrogen fluoride containing only relatively small quantities of water, to form f-butyl-benzene, but diisobutylene with 70% hydrogen fluoride produced p-f-octylphenol. Cyclohexene reacted with toluene to form cyclohexyl-toluene and octene-1 rapidly reacted with toluene to form 2-octyltoluene (Simons and Basler, 31). 

Figure 5.7. There are many examples now known of the synthesis of NPs via matrix pathways (see also Figure 9.3). However, a nice example of the benefit of such flexibility was revealed when a mutant of spearmint that had smelled more like peppermint was studied.A comparison of the terpenes in both plants revealed that the single gene mutation had not resulted in a single chemical change but multiple changes, in the mutant plant, a hydroxyl group was added to the 3-position of the cyclohexene ring of limonene while the wild-type hydroxylated the 6-position. Some of the other wild-type tailoring enzymes in the mutant did not discriminate fully between the 3- and 6-hydroxylated products so a new family of NPs were produced which gave the mutant plant an odour of peppermint.

Alkylation of allylic alcohols. The alkylation of allylic alcohols by Grignard reagents in the presence of nickel-phosphine -2 catalysts has been shown to be ttereospecific in the case of the cis- and /rans-4-methyl-2-cyclohexene-1 -ols (2) . The hydroxyl group is replaced with inversion, but the regiosclcctivity is different. In... 

While there are few examples of conjugate additions of either a-oxygen- or a-silyl-stabilized carbanions, Tamao and Posner have reported two hydroxymethyl synthons ["ClfcOH] (246 and 247) which show synthetic promise. Additions with the silicon-based synthon (246) is restricted to 2-cyclohexen-l-ones and work-up requires a successive acid and base procedure that is incompatible with sensitive molecules,188a-b while the tin-based synthon (247) is more versatile and the hydroxyl group is obtained under neutral conditions (Scheme 83).,88c... 

In a related reaction, stereochemical control during epoxidation of A4- .v-l, 2-disubstituted cyclohexenes 141 with MCPBA depends upon the hydroxyl functionality195. A free alcohol (141a) or an acetate (141b) affords. vyw-cpoxides exclusively. Epoxidation of a t-butyldimethylsilyl ether (141c) gives predominantly the rmtf-cpoxide (54%). 

A clean, solvent-free method has been developed for the bis-hydroxylation of alkenes by the use of Nafion-based acidic catalysts and 30% H202.655 Nafion NR50 and SAC-13 exhibited high activity in the oxidation of isomeric C alkenes, cyclohexene [Eq. (5.228)], 1,4-cyclohexadiene, and allylic alcohols in the temperature... 

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