Trans-l ,3-cyclohexanediol

Stoddart and his coworkers have reported syntheses of the trans-syn-trans and the trans-anti-trans isomers of dicyclohexano-18-crown-6 The synthesis of these two compounds from trans-l,2-cyclohexanediol was accomplished in two stages. First, the diols were temporarily linked on one side by formation of the formal, and this was treated with diethylene glycol ditosylate and sodium hydride to form the hemi-crown formal. Removal of the formal protecting group, followed by a second cychzation completed the synthesis. The synthesis of the trans-anti-trans compound is illustrated below m Eq (3 12) and the structures of the five possible stereoisomers are shown as structures 1—5. 

A. trans-l,2-Cyclohexanediol. In a 100-ml., round-bottomed flask equipped with a reflux condenser protected with a drying tube are placed a magnetic stirring bar, 17.56 g. (0.0667 mole) of thallium (I) acetate (Note 1), and 40 ml. of dried acetic acid (Note 2). The mixture is stirred and heated at reflux for 1 hour. To the cooled mixture are added 2.84 g. (3.5 ml., 0.0346 mole) of cyclohexene (Note 3) and 8.46 g. (0.0333 mole) of iodine (Note 4). The resulting suspension is stirred and heated at reflux for 9 hours (Note 5), and then cooled to room temperature. The yellow precipitate of thallium(I) iodide is filtered and washed thoroughly with ethyl ether. The filtrates are comhined, the solvents are removed under reduced pressure with a rotary evaporator (Note 6), and the residual liquid is dissolved in dry ethyl ether. The turbid solution is dried with anhydrous potassium carbonate, and the solvent is again removed by rotary evaporation (Note 6), affording 5.4-6.3 g. of trans-1,2-cyclohexanediol diacetate as a mobile, brown liquid (Note 7). 

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. ... 

High levels of asymmetric induction can be achieved intramolecularly if the substrate functionality and the heteroatom ligand are contained in the same molecule. Chiral amido(a]kyl)cuprates derived from allylic carbamates [(RCH= CHCH20C(0)NR )CuR undergo intramolecular allylic rearrangements with excellent enantioselectivities (R = Me, n-Bu, Ph 82-95% ee) [216]. Similarly, chiral alkoxy(alkyl)cuprates (R OCuRLi) derived from enoates prepared from the unsaturated acids and trans-l,2-cyclohexanediol undergo intramolecular conjugate additions with excellent diasteroselectivities (90% ds) [217]. 

If 1-trimethylsiloxy-l-cyclohexene (193) is treated with borane/THF, hydrogen peroxide/alkali and then hydrolyzed, trans-l,2-cyclohexanediol (203) is obtained137 but trans-1 -hydroxy-2-trimethylsiloxycyclohexane (202) can be isolated without subsequent acid-catalyzed hydrolysis138 whereas the direct hydrolysis of the borane adduct 204 leads directly to cyclohexene (205)139K Very interesting is the use of TiCLt as catalyst. 193 plus benzaldehyde and TCI4 gives after hydrolysis 2-[hydroxy-(phenylmethyl)] cyclohexane-1-one (206)l40 ... 

Although carbinols were found not to be oxidized by lead tetraacetate in acetic acid, they were attacked in less polar solvents, and glycol-cleavage was also more rapid in these solvents23 for example, the rate of oxidation of trans-l, 2-cyclohexanediol in tetrachloroethane was 5,000 times that in acetic acid. The kinetics was no longer true second-order in the media of low polarity, but approached this state as the concentration of acetic acid... 

The diacetate is dissolved in 25 ml. of 95% ethanol, a solution of 2.9 g. (0.073 mole) of sodium hydroxide in 11ml. of water is added, and the resulting mixture is heated under reflux for 3 hours. The solution is concentrated by rotary evaporation under reduced pressure, and the remaining syrup is extracted with six 50-ml. portions of chloroform. The combined extracts are dried over anhydrous magnesium sulfate and evaporated, providing 3.1-3.3 g. of a pale brown crystalline solid that melts at 97-103°. Recrystallization from carbon tetrachloride gives 2.5-2.7 g. (65—70% based on iodine) of trans-l,2-cyclohexanediol, m.p. 103-104° (Note 8). 

Figure 21.10 CC chromatogram showing the separation of enantiomeric sec-phenethyl alcohol, 1-phenyl-1-butanol, and trans-l,2-cyclohexanediol. Chromatographic conditions fused-silica capillary column (8m, 250pm ID) coated with (lS,2R)-(H-)-N,N-dimethylephedrinium-...

STEREOSELECTIVE HYDROXYLATION WITH THALLIUM(I) ACETATE AND IODINE trans- AND cis-l,2-CYCLOHEXANEDIOLS... 

Reaction of trans-1,2-cyclohexanediol with para-formaldehyde in the presence of Indion 130 as catalyst to yield the corresponding cyclic formal has been successfully carried out (Matkar and Sharma, 1995). A conversion of 52% was realized with 70% selectivity towards cyclohexanediol formal the other side products are rrans-hexahydrobenzo-l,3,5-trioxypin, di(tra i -2-hydroxycyclo-hexyloxy) methane. 

In 1994, Hanessian and co-workers [50] reported the first examples of metal-free three-dimensional triple-stranded helicates through spontaneous self-assembly of chiral C2-symmetrical diols and chiral C2-symmetrical diamines. The initial observation resulted from the utilization of enantiopure C2-symmetrical vicinal trans-1,2-diaminocyclohexane [51,52] as ligands in the asymmetric dihydroxylations of olefins [53] and as reagents for asymmetric synthesis [54], When equimolar amounts of (5,5)-frfl x-l,2-diaminocyclohexane (28) and its (i ,i )-enantiomer (29) were individually mixed with (5,5)-frfl x-l,2-cyclohexanediol and heated in refluxing benzene, crystals of the respective supraminol complexes 28 30 and 29 30 were formed quantitatively (Scheme 12). This was the physical basis for the separation of racemic diols with tr[Pg.104]

Unlike the complex 39 36, the complex 39 40, formed with the mismatched diol, consists of a vastly interlinked layered H-bonded network that is in part reminiscent of the crystal structure previously observed for (R,R)-trans- 1,2-diaminocyclo-hexane and mexo-l,2-cyclohexanediol (Figure 47, Scheme 17). The efficiency of 39 to recognize the mismatched diol suggests that acyclic diamines are the optimal candidates for the molecular recognition of sterically demanding diols with respect to the cyclic diamines. In fact, (i ,i )-tra x-l,2-diaminocyclohexane did not recognize mismatched 39 40. 

Assuming the pleated sheet-like motif and the ribbon-like motif as reference H-bonded core structures, a further increase in the steric demand of the residues, as for example the presence of aromatic rings as substituents on the diol or diamine moiety, or the absence of the required trans configuration, lead to a loss of efficiency in the recognition process with formation of incomplete ribbon-like or staircase-like structures. In the latter cases, competition experiments show that matched complexes with the pleated sheet-motif or with the ribbon-like motif of the core crystallize more easily than those characterized by incomplete or low organized core structures. Thus, when the complex 29 38 was melted with 1 equiv. of (i ,i )-tra x-l,2-cyclohexanediol (31) and the mixture was crystallized from benzene, again 29 31 was obtained as the only crystalline product (Scheme 22) [60]. 

Evaporation of the mother liquor and treatment of the residue under similar experimental conditions afforded ( )-(—)-34 in a yield of 57% with an optical purity of 62%. Optically active threo-1,2-diamino-1,2-diphenylethane was also an effective diamine for the optical resolution of racemic 34 that was obtained in a yield of 78% with an optical purity of 92% [70]. As previously described, the optical resolution of racemic trans-1,2-cyclohexanediol could be performed under similar experimental conditions [27]. Notably, this procedure was found effective also for the optical resolution of hydroxy oximes. Thus, when equimolar amounts of racemic ( )-l,2-diphenyl-2-(hydroxyimino)ethanol (50) and (R,R)-29 were added to benzene and crystallized, (7 )-(—)-( )-50 was recovered in a yield of 56 % based on the enantiomer in the racemate (Scheme 24) [27]. 

The reaction between 0s03py2 , and K2[0s02(0Me)4] or K[0s02(0Ac)3] and R(OH)2 normally occurs only with acyclic 1,2-diols and cyclic cis 1,2-diols trans 1,2-diols do not react with the exception of trans-1,2-cyclohexanediol and trans-1,2-cycloheptanediol.4 0 Behrman showed that /ra7 -thyminediol, trans-thymidinediol and tra j-l,3-dimethylthyminediol did react, albeit slowly,... 

Troyansky etal. reported that homolytic cycloaddition of dithiols derived from trans- and r-l,2-cyclohexanediols to alkynes, induced by Pr3B-02, offered an extremely simple approach to trans- and m-cyclohexano-fused 12-membered crown thioethers <1995TL11431>. The reaction of 22 (A,A) proceeded with a pronounced remote 1,6-asymmetric induction to give predominantly 23 (1A, 6R, 12A), while 25 (A, R) reacted nonstereoselectively (Scheme 2). 

Payne and Smith59 studied the hydroxylation of cyclohexene with a mixture of 34% hydrogen peroxide and a little tungstic acid in acetone. In addition to trans-1,2-cyclohexanediol, they obtained a 25% yield of 3,3-dimethyl -1,2,4-trioxaacetone derivative of the intermediate hydroxyhydroperoxide. Hydrogenation of 71 leads to tm w-cyclo-hexane-l,2-diol. 

As noted at the end of Section 7.8, the prefixes cis- and trans- would be ambiguous when naming the diols derived from 1-methyicyclohexene because the ring has three substituents. Instead, a reference substituent r is chosen and other substituents are eitlier cis (c) or trans (t) to that reference. For the two l-met)iyT-l,2-cyclohexanediol isomers, the -OH group at Cl is the reference (r-l), and the —OH at C2 is either cis (c-2) or trans (f-2) to that reference. Thus, the diol isomer derived bv cis hvdroxvlation is named l-mcthvi-r-l,c-2-cvclohexanediol, and the isomer derived by trans hydroxyl-ation is named l-metliyl-/-l,t-2-cyclohexanediol. 

The stereochemistry of the diols often affects the yields of carbonyl compounds. Thus, the oxidation of cis-l,2-cyclohexanediol with sodium bismuthate in aqueous phosphoric acid and ether at 30 C gives only 23% of adipic aldehyde, whereas the trans isomer gives a 49% yield [483] (equation 303). 

The method described is essentially that of Swem, Billen, Findley, and Scanlan. /mM5-l,2-Cyclohexanediol also has been prepared by hydrolysis of cyclohexene oxide. j-l,2-Cydo-hexanediol has been prepared by the reaction of cyclohexene with hydrogen peroxide in tertiary butyl alcohol with osmium tetroxide as a catalyst. Hydrogenation of catechol over Raney nickel catalyst at 150° gives a mixture (m.p. 73-77°) of cis- and trans-1,2-cyclohexanediols. ... 

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