Cyclohexane derivatives diols

Diels-AUer reactions. This diene can serve as a precursor to the highly oxygenated cyclohexane derivative shikimic acid (3), as shown in Scheme 1. Oxidative desilylation of the Diels-Alder adduct 2 could not be effected with peracids, but was effected by cis-dihydroxylation (Upjohn procedure, 7, 256-257) followed by p-elimination of (CH3)3SiOH with TsOH. Introduction of the 4a,5P diol system was effected indirectly from the 4a,5a-epoxide in several steps, since direct hydrolysis of the epoxide resulted in a mixture of three triols.1... 

The 1,4-elimination of 193, given in the Eqs. 52 and 53, represents two pathways leading to two different iminium ions 194 and 195, whose relative distribution will depend on whether the reaction is performed under thermodynamic or kinetic control. The species 194 is a cyclooctene derivative and the species 195 a cyclohexane derivative. The cyclohexane derivative 195 must, of course, predominate in a thermodynamically controlled reaction. Like the species 193, the species 196 also represents two pathways for 1,4-elimination as shown in Eqs. 54 and 55. Fortunately, both the pathways yield the same product 197. The reactions shown in Eqs. 56 and 57 are examples of elimination resulting from the 1,3-diol mono-tosylate system. An electron pair orbital on the hydroxylic oxygen that is antiperiplanar to the cleaving central ac c bond provides the necessary electronic push in which the former makes the latter weak, and therefore labile for cleavage. The reaction shown in Eq. 57 was used by Corey and coworkers in a synthesis of... 

Nonenolizable 1,3-dicarbonyl compounds are reduced in good yields to the corresponding diols. Thus, the spiro cyclohexane derivative 1 is reduced to cw-4,8-dihydroxy-6,6-dimethyl-spiro[2.5]octane [2, d.r. (cis/trans) 99 1 ]175 lithium aluminum hydride reduction gives a d.r. cisjtrans) 33 67. These results are explained by the formation of a thermodynamically favorable cyclic cis-aluminate. 

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. 

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. 

The stereochemistry of ring C in taxicin-I has been studied (19, 20a) by using the cyclohexane derivatives which are available (16) from periodate cleavage reactions. Their relations are shown in Chart I. Cleavage of 0-cinnamoyltaxicin-I gives a dialdehyde which, on reduction with sodium borohydride, affords the diol LXXVII, 0-/S-Phenyl-... 

Microbial oxidation of benzene derivatives producing benzene cu-diols have been utilized in the preparation of 6-p-hydroxyshikimic acid, polyhydroxylated cyclohexane derivatives related to cyclophellitol and carba-a-L-fucose. It is worth noting here that the meso-6 o produced by oxidation of benzene itself has been resolved with a lipase giving (li , 2S)-l-acetoxy-2-hydroxycyclohexane-3,5-diene in >95% e.e. ... 

Cyclopentene-l-carboxaldehydes are obtained from cyclohexene precursors by the sequence cyclohexene - cyclohexane-1,2-diol -> open-chain dialdehyde - cyclopentane aldol. The main advantage of this ring contraction procedure is, that the regio-and stereoselectivity of the Diels-Alder synthesis of cyclohexene derivatives can be transferred to cyclopentane synthesis (G. Stork, 1953 G. BUchi, 1968). 

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). 

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-... 

It was independently found by two groups that the exo-diol derived from bis(camphorsulfonyl)-substituted tra .s-cyclohexane-1,2-diamine ligand (HOCSAC) was an excellent promoter for the enantioselective addition of dialkyIzinc reagents to any type of ketones, even dialkyl ketones, in the presence of Ti(Oi-Pr)4. As shown in Scheme 4.11, excellent enantioselectivities of up to 99% ee were obtained in these conditions in combination with high yields and with a low catalyst loading of 2-10 mol%. 

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. 

The fluorescence In dilute solution is measured for five polyesters with terephthalate as the rigid aromatic unit and diols derived from cyclohexane as the flexible spacer, A conformational analysis concludes that the spacers most conducive to excimer formation are the 1,3-c/s-cyclohexanediol and 1,4-e/s-eyclohexanedimethanol. This result from calculations is compatible with experimental results. 

Cyclohexanediol and derivs 3 C595—C596 cyclohexane- 1,2-diol dinitrate 3 C596... 

TABLE 9. Conformational structures (a) and Newman projection diagrams (b) of (IS,25)- and (IR,2ft)-cyclohexane diol. Bis-p-dimethylaminobenzoate derivatives (c), bisignate CD Cotton effect data and torsion angles (d)14... 

The aminolyses of the carbonates derived from cyclopentane-1,2-diol (38) and cyclohexane-1,2-diol (39) by hexylamine at 70 °C were much slower than that of ethylene carbonate, the latter (39) being about twice as reactive as the former (38). Computational calculations confirmed that ring strain was the main determining factor.40... 

Benzylidene and isopropylidene acetals are often used for the selective protection 1,2-cis or 1,3-cisjtrans diols of sugar derivatives. They are stable to strong basic conditions but quite fragile towards acid. Recently, dispirodiketal and cyclohexane-1,2-diacetal groups have been introduced to protect selectively 1,2-trans diols of carbohydrates. 

Table XI. Conformational structures (a and b) and Newman projection diagrams (c and d) of (15,25) and (lR,2R)-cyclohexane diol (a) and their bis-p-dimethylaminobenzoate derivatives (b). CD data for the bisignate Cotton effects of the latter are shown below.

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