1.2- Cyclohexanediol synthesis

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. 

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]

Bernard A, Arosio D, Manzoni L, Micheli F, Pasqnarello A, Seneci P. Stereoselective synthesis of conformationally constrained cyclohexanediols a set of molecnlar scaffolds for the synthesis of glycomimetics. J. Org. Chem. 2001 66 6209-6216. Arosio D, Vrasidas I, Valentin P, Liskamp RM, Pieters RJ, Bemardi A. Synthesis and cholera toxin binding properties of mnltivalent GMl mimics. Org. Biomol. Chem. 2004 2 2113-2124. 

Photooxidation rates of propan-2-ol in aqueous Ti02 suspensions are reported to be increased by ultrasound radiation, an observation which has been rationalised in terms of mass transport of the substrate and activation of the solid catalyst. The value of the newly described photochemical rearrangement of 2-phenylthio-l,3-cyclohexanediols such as (69) to deoxysugars (70) which are in equilibrium with the closed form (71) has been illustrated by its application to the synthesis of (+)-m-rose oxide (72), and the same authors have also described the regioselective photorearrangement of 2-phenylthio-3-aminocyclohexanols (73) to deoxyazasugars (74) this has proved to be useful in the synthesis of various piperidines (75), amino-sulfones, -sulfoxides and -acids. Hydroxy(alkoxy)methyl radicals have been generated by photo-induced electron transfer. ... 

Scheme 8.5 Synthesis of trans-1,l-cyclohexanediol from cyclohexene...

One interesting aspect of asymmetric catalysis is that sequential reactions with a chiral catalyst can often lead to an enhancement in the enantioselectivity over a single transformation with the same catalyst in a process called kinetic amplification. Doyle was able to exploit this phenomenon in the synthesis of novel tricyclic products from the bis-diazoacetate of irans-1,4-cyclohexanediol (56, Scheme 12) [71]. Although formation of C2-symmetric product 58 was expected, resulting from the typically preferred five-membered insertion event, it was found that 57 could be produced preferentially with appropriate choice of catalyst, and with very high ee (95-99%). Bis- )-lactone 59 was never the major product, but could be formed as up to 34% of the product mixture. Notably, similar catalyst-controlled mixtures of [1- and y-lactone products were also obtained with diazoacetates derived from cholesterol derivatives [72],... 

The most popular lands of the diols for asymmetric synthesis are bis-secondary diols that have a C2 axis of symmetry [212]. The presence of the symmetry axis avoids the formation of diastereoisomeric esters or acetals [213], (1R, 27 )-Cyclohexanediol 1.34 (n = 1) has been used as an auxiliary in asymmetric cyclopropanation [214] and (IS, 2S)-cycloheptanediol 1.34 (n = 2) in 1,4-addition of cuprates[157], Dioxolane derivatives of 1.34 have been used for asymmetric P-ketoester alkylations [215] and cuprate 1,4-additions [216]. Linear 1,2-diols 1.35 (R = Me, i-Pr, c-CgH j, Ph) and functionalized 1,2-diols 1.36 (Y = COOalkyl, CONR 2, CH2OR ) are readily available from optically active tartaric acids 1.36 (Y = COOH). Acetals derived from these diols are valuable reagents m asymmetric synthesis [173, 213, 217], as the related 1,3-diols 1.37. Acetals of 1,3-butanediol 137 (R = Me, R = H) have also been used. When these acetals are formed from aldehydes under thermodynamic conditions, one 1,3-di-oxane stereoisomer often predominates. In this favored isomer, the substituent from the aldehyde and the methyl group from 1.37 are both in equatorial orientar... 

There are few reports of successful one-step synthesis of primary diamines, and the examples are limited to amines with a special structure. Amination of 1,4-cy-clohexanediol in supercritical ammonia (135 bar) over a Co-Fe catalyst alforded 67 % 1,4-diaminocyclohexane [21]. Excess ammonia, as both supercritical solvent and reactant, and short contact time in the continuous fixed-bed reactor favored the desired reactions. In the best example the cumulative selectivity for the diamine and the intermediate amino alcohol was 97 % at 76 % conversion. Recycling of the unreacted diol and amino alcohol can provide an alternative to the eurrent process, the hydrogenation of pnra-phenylenediamine. The high seleetivity was because of the rigid structure and the relative positions of OH functionality in the substrate. For comparison, amination of 1,4-butanediol under similar conditions yielded pyiTolidine as the major product 1,4-diaminobutane was barely detectable. When 1,3-cyclohexanediol was aminated with the same catalyst in the continuous system, the yield of 1,3-diaminoeyclohexane dropped below 5%, mainly because elimination of water led to undesired monofunctional products via a,/9-unsaturated alcohol, ketone, and/or amine intermediates [22]. 

Treatment of a diol with chlorodiphenylphosphine in the presence of triethylainine or pyridine leads to diphosphinites. By this easy method, (S,S)-1,2-bis(diphenylphosphinoxy)cyclohexane (CHDPPO, 59) was obtained from (S,S)-l,2-cyclohexanediol (Section 4.1.2)23 58 and (5,S)-2,4-bis(diphenylphosphinoxy)pentane [(S,S)-BDPOP, (S.SV60] from (S,S)-2,4-pentanediol (Section 4.I.2.)59. In ref 59, the synthesis is described in detail from the beginning, i.e., the asymmetric synthesis of the diol by catalytic reduction of the diketone with Raney nickel modified with tartaric acid/sodium bromide. 

Finally, reaction E in Fig. 4 illustrates a stereoselective synthesis that proceeds by differentiation of two enantiotopically related groups of a meso compound. Here, one hydroxyl group of d.s-1,2-cyclohexanediol is preferentially benzoylated in the presence of one molar equivalent of an enantiomerically pure diamine [26]. These desymmetrization reactions (that have many biological versions) are also called meso-tricks , and are currently receiving a great deal of attention for the preparation of new chiral building blocks [27]. 

A. Synthesis of o to-dikydroxyl PCL e-CL (20.00 g, 175.22 mmol), 1,4-cyclohexanediol (0.14 g, 1.17 mmol), stannous octanoate (0.47 g, 1.17 mmol) and anhydrous toluene (45 ml) were place in a round bottom flask complete with condenser under an argon atmosphere. The reaction mixture was then heated at 110 °C for 24 h before being diluted with THE and precipitated into cold MeOH. The precipitated polymer was collected by filtration and dried in vacuo (0.05 mmHg) to afford a white powder (19.44 g, 97%). 

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