Cyclohexane-1,3-diols, reactions with

Another example of a [2s+2sh-1c+1co] cycloaddition reaction was observed by Barluenga et al. in the sequential coupling reaction of a Fischer carbene complex, a ketone enolate and allylmagnesium bromide [120]. This reaction produces cyclopentanol derivatives in a [2S+2SH-1C] cycloaddition process when -substituted lithium enolates are used (see Sect. 3.1). However, the analogous reaction with /J-unsubstituted lithium enolates leads to the diastereoselective synthesis of 1,3,3,5-tetrasubstituted cyclohexane- 1,4-diols. The ring skeleton of these compounds combines the carbene ligand, the enolate framework, two carbons of the allyl unit and a carbonyl ligand. Overall, the process can be considered as a for-... 

There are few examples of other allowed sigmatropic shifts involving six ten electron transition states, but these are not common reactions. A [3, 4] shift is observed in competition with a [1, 2] shift in cations derived from cyclohexane diols. This is a cationic equivalent of the Cope rearrangement,... 

In principle, a number of different types of acetal or ketal might be produced. In this section, we want to exemplify a small number of useful reactions in which two of the hydroxyl groups on the sugar are bound up by forming a cyclic acetal or ketal with a snitable aldehyde or ketone reagent. Aldehydes or ketones react with 1,2- or 1,3-diols under acidic conditions to form cyclic acetals or ketals. If the diol is itself cyclic, then the two hydroxyl groups need to be cA-oriented to allow the thermodynamically favourable fused-ring system to form (see Section 3.5.2). Thus, dx-cyclohexan-1,2-diol reacts with acetone to form a cyclic ketal, a 1,2-O-isopropylidene derivative usually termed, for convenience, an acetonide. 

We have observed that diol 3, cis-2-butene-l,4-diol, and cis-1,2-bis(hydroxymethyl)cyclohexane react smoothly with TPP-CClq to afford 4 (78%), 2,5-dihydrofuran (65%), and cis-8-oxabicyclo[4.3.0]-nonane 84%). Reaction of diol 5 with TPP-CCli in CH3 CN gives 52% of 5-chloropentanol, 6 (11%), and 1,5-dichloropentane (25%) while diol 7 affords 6-chlorohexanol (48%) and 1,6-dichlorohexane (39%). Comparisons of the ether chlorohydrin dichloride product distributions arising from these simple diols reveal a trend for efficiency of chain closure to 3 - 7 membered rings where the formation of cyclic ethers appear to decrease in order of the following ring size 3-5>6>4-7. 

ROM—>RBr. In the cyclohexane series reaction of diols with PBr is attended with rearrangements. Thus treatment of the 1,3- and 1,4-cyclohexanediols with PBrj affords mixtures of cis- and trans-1,3- and l,4-dibromides. Eliel and Haber found that cu-d-i-butylcyclohexanol reacts with PBr to give trani-4-/-butylcyclo-hexyl bromide, together with a small amount of olefin and a mixture of dibromides. Thus PBr, is evidently superior to PBr, for conversion of secondary alcohols into bromides. However, the Hunsdiecker reaction seems to be the method of choice for preparation of cyclohexyl bromides. ... 

Epoxides from vic-diols. trans-1,2-Dihydroxycyclohexane (1) reacts with dimethylformamide dimethyl acetal at 75° (24 hours) and then at 130° (24 hours) to give <7.f-cyclohexene oxide (2) in 88% yield. The analogous reaction with cis-dihydroxycyclohexune (3) yieIJs dimethylformamide cyclohexane acetal (4). 

McCasland and coworkers,which developed the theoretical basis for this type of reaction in cyclohexane derivatives, has been extensively applied to synthetic work in the carbohydrate field by Baker, Goodman, and their CO workers. The conversion of trans amino alcohols (106, Z = OH, Y = NHa) to the cis derivatives (109, X = OH, Y = NHo), through the AT-acetyl O-(methylsulfonyl) derivatives (107, Z = OS02Me, RCXY = MeCONH), with hydrolysis of the cyclic ion intermediate (108), is of general applicability. The conversion of (mns-diols to cfs-diols by this procedure is feasible with cyclohexane derivatives, but has not yet been developed as a general reaction with sugar derivatives, which are much less reactive. 

Ionic strength and specific ion effects have been investigated in the oxidation of mandelic acid by cerium(iv) sulphate. Unlike the reaction in HCIO4 where there is spectrophotometric and kinetic evidence for complex formation, under these conditions there is a first-order rate dependence of both oxidant and reductant. The replacement of H+ by Li+, Na+, or K+ produces only a minor change in rate and has no effect on the activation parameters. Rate laws which are essentially similar have been established in the reactions with cyclohexane-1,4-diol cyclopentanone, and methyl isopropyl ketone. The enol form of the substrate is favoured as the active reagent in the latter two reactions. 

Miscellaneous Cyclohexanes. Various reactions involving hydroxylation of cyclohexane derivatives have been reported. The reaction of cyclohexanol with Fe(C10 )2 and hydrogen peroxide in acidic aqueous MeCN solutions has been shown to be very sensitive to the exact concentrations of Fe", Fe ", and perchloric acid. In MeCN, cis-cyclohexane-l,3-diol forms 72% of the product diol, i.e. hydrogen removal at C-3 occurs with some stereoselectivity cis to the hydroxy-group. In highly aqueous solutions, the dominant oxidation site is at C-4. Evidence is presented for a stepwise process involving an initial directed hydrogen abstraction, oxidation of the radical by Fe" , and stereoselective carbonium ion capture. 

Note that since the melting points of 1,4- and 1,2-cyclohexane diol are 98°C and 75°C, respectively, and they have high volatility, these could not be employed as single chain-extender systems as the diols tended to volatilize from the mixture and condense on the walls of the reaction vessel. These diols were therefore blended with other liquid diols (e.g. 1,4-butane diol) which act as a solvent for the main diol. 

Alkylation Reactions. DMF dialkyl acetals undergo a variety of reactions with 1,2-diols. For example, the reaction of trans-cyclohexane-l,2-diol with DMF dimethyl acetal leads to the formation of cyclohexane epoxide (eq 2) with inversion of configuration. Similarly, wej 0-l,2-diphenyl-l,2-ethanediol gives trans-stilbene epoxide stereospecifically (eq 3). This method has also been applied in the synthesis of cholestane epoxide from vicinal diols. If the intermediate 2-dimethylamino-1,3-dioxolane is treated with Acetic Anhydride, reductive elimination to the alkene occurs with retention of stereochemistry (eq 4). " ... 

The substitution pattern in the enolate is crucial for the ring size of the cyclization product. Upon reaction with carbene complex 58 /3-substituted lithium enolates 59a H) lead to densely substituted cyclopentanols 60 suggesting a [2-i-2-i-l]cycloaddition pathway. /3-Unsubstituted lithium enolates 59b (R =H), however, form 1,3,3,5-tetrasubstituted cyclohexane-l,4-diols 61 that indicates a [2-I-2-I-1-I-1] sequence [41]. The branching point in the mechanism seems to be intermediate B formed upon addition of the allyl magnesium bromide to penta-carbonylchromate intermediate A. Intermediate B formed from /3-substituted enolates 59a is supposed to undergo an intramolecular carbometallation reaction to give cyclopentanol derivative 60. In contrast, intermediate B originating from... 

To gain an insight into the likely hydrolytic behavior of sulfated simple sugars and polysaccharides, Brimacombe, Foster, Hancock, Overend, and Stacey carried out a rigorous set of experiments with the cyclic sulfates of cyclohexane cis-and trims-1,2-diol as model compounds. The results were interpreted on the reasonable assumption that, in all cases, the cyclic sulfates initially afford a diol monosulfate. Examples of both S-0 and C-0 bond cleavage were encountered. A qualitative reaction mechanism was proposed for use as a working hypothesis for the hydrolysis of sugar sulfates. 

In connection with our own work on the enzyme-catalysed hydrolysis of cyclohexene epoxide with various fungi we made the unexpected observation that the microorganism Corynesporia casssiicola DSM 62475 was able to interconvert the (1R,2R) and (1S,2S) enantiomers of the product, trans cyclohexan-1,2-dioI 25. As the reaction proceeded the (1R,2R) enantiomer was converted to the (1S,2S) enantiomer [20]. If the racemic trans diol 25 was incubated with the growing fungus over 5 days, optically pure (> 99 % e. e.) (1 S,2S) diol 25 could be isolated in 85% yield. Similarly biotransformation of cis (meso) cycIohexan-1,2-diol 26 yielded the (1S,2S) diol 25 in 41 % (unoptimized) yield (Scheme 11). 

For the cyclization of dialdehydes, however, its utility seems limited. Being a nitromethane addition product, it can readily undergo retro-nitromethane addition with alkali to give formaldehyde and nitromethane. Thus, it is not surprising that reaction of glutaraldehyde with 2-nitroethanol under the usual conditions (i.e. 1 molar equivalent of sodium hydroxide in aqueous ethanol) should yield 2-nitrocyclohexane-1,3-diol 5), a nitromethane cyclization product With catal5dic amounts of sodium hydroxide (pH 8—9), however, 1-hydroxymethyl-l-nitro-cyclohexane-2-6-diol (80) can be isolated in yields of 24—29%... 

By choosing an appropriate titanium complex, a /ra r-isomer of 1,2-cyclohexanols can be prepared selectively. Because intramolecular pinacol coupling of hexanedials with Sml2 usually produces t-isomers of cyclohexane-1,2-diols, the titanium-mediated reaction complements the samarium-mediated cyclization (Equation (17)). In addition, when a /-butyl group fixes the conformation of the substrate, one of the diastereomers is produced selectively (Equation (18)). ... 

---