Cyclization cyclohexanol

Finally, reaction of primary, secondary, or tertiary alcohols 11 with Me3SiCl 14 in the presence of equivalent amounts of DMSO leads via 789 and 790 to the chloro compounds 791 [13]. n-Pentanol, benzyl alcohol, yS-phenylefhanol or tert-butanol are readily converted, after 10 min reaction time, into their chloro compounds, in 89-95% yield, yet cyclohexanol affords after reflux for 4 h cyclohexyl chloride 784 in only 6% yield [13] (Scheme 6.5). 1,4-Butanediol is cyclized to tetrahydrofuran (THF) [13a], whereas other primary alcohols are converted in 90-95% yield into formaldehyde acetals on heating with TCS 14 and DMSO in benzene [13b] (cf also the preparation of formaldehyde di(n-butyl)acetal 1280 in Section 8.2.1). 

An interesting stereochemical profile of this cyclization is that in the five-membered product structures, substituents PhS and OH groups are placed cis to each other, whereas in six-membered products the placement is trans (Table 6, entry 7). The cis selectivity in the five-membered ring systems is not affected by a and fi-substituents of the alkoxides (entries 2, 3 and 4), indicating that the steric effect is not the dominant factor. Instead, interaction between the oxido and carbene center composes a five- (or seven-) membered transition state 28, which allows the carbene to abstract the nearest quasi axial hydrogen as a hydride to produce a carbonyl intermediate 29, leading to the cyclization products 27 and 30 (Scheme 13, Eq. 1). Similarly, the stereoselective stepwise cyclization of cis- and rra s-2-(3,3-dithiopropyl)cyclohexanol to 2-phenylthio-... 

Fig. 27 The N-oxide hapten [74] was used to elicit mAb 6D4 which catalysed the cyclization of [72] to form the cyclohexanol [73],...

The cyclizations of cis- and lrans-2-hydroxymethyl-l-cyclohexylamine and cis- and lram-2-aminomethyl-l-cyclohexanol with 4-nitrobenzaldehyde have been studied by means of H NMR spectroscopy in CDCI3 solution (90ACSA364 91T2229). The time-dependent spectra confirmed that the reactions of all these amino alcohols proceeded via Schiff bases. With the exception of cis-2-hydroxymethyl-l-cyclohexylamine, the thermodynamically more stable perhydrobenzoxazine epimer is also the kinetically favored product. In the former case, from amino alcohol 21 (R = H), the Schiff base 37 with N-outside predominant conformation is formed first due to kinetic control, the less stable epimeric ring form 38 is obtained with N-outside predominant conformation. The thermodynamically controlled product 33 is formed subsequently, via the less stable open-chain form 37, in a slow equilibration process (90ACSA364). 

Pankova and Tichy prepared all four stereoisomeric 4-rerr-butyl-2-aminomethyl-l-cyclohexanols and cyclized them with ethyl benzimidate to hexahydro-l,3-benzoxazines 158-161 (74CCC1447). From the A-acyl O-mesylate derivatives 162 and 163 on thermal cyclization or thionyl chloride treatment, ring closure occurred with inversion and resulted in 158 and 159 (74CCC1447). 

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)). ... 

The 4-exo cyclization of open-chain substrates 63 proceeds in trans-fashion with moderate to excellent selectivity (trans/cis = 77/23 > 99/1 )90. The trans selectivity is dependent on the substitution pattern of R2, R3 and R4. The reactions giving trans-l-aza-2-silacyclobutanes 65 have been applied to the stereoselective syntheses of syn-amino alcohols 66 via the Tamao oxidation as exemplified by the reaction of 63d (R = HMe2Si), affording 66d (76% overall yield in 4 steps, syn/anti = > 99/1) via 65d (trans/cis = > 99/1) in equation 2690. In the case of 3-iV-disilylamino-l-cyclohexene 63f (R = HMe2Si), however, cis-l-aza-2-silacyclobutane 65f is formed exclusively, that is converted to ds-2-amino-l-cyclohexanol (66f) (equation 27)90. 

Treatment of epoxide (34) with Bu3SnH/AIBN in the presence of Mgl2 first forms iodohydrin synthon, which rapidly reacts with Bu3Sn to form a cyclohexanol derivative (35) via 6-exo-trig ring closure of (3-hydroxyl radical as shown in eq. 3.12 [50-54]. Since the epoxides can be obtained from alkenes with peroxides, this is an indirect radical cyclization method of alkenes. 

Indium trichloride mediates the intramolecular cyclization of the prochiral allylstannyl diketone to afford the desymmetrized cis-cis cyclohexanol predominantly (Equation (36)). The use of TiCU in place of InCl3 gives the cis-trans diastereomer.213... 

Palladium-catalyzed cyclization-carboalkoxylation of alkenyl indoles tolerated substitution along the alkenyl chain and at the internal and tfr-terminal olefinic position. In addition to 2-(4-alkenyl)indoles, 2-(3-alkenyl)-, 2-(5-hexenyl)-, 3-(3-butenyl)-, and 3-(4-pentenyl)indoles also underwent efficient palladium-catalyzed cyclization-carboalkoxylation to form the corresponding tricyclic indole derivatives in moderate to good yield with excellent regioselectivity. By employing this procedure, efficient palladium-catalyzed cyclization-carboalkoxylation of 2-(4-pentenyl)indole with ethanol, 1-octanol, 2-propanol, and cyclohexanol was achieved. 

In the analogous stoichiometric reaction, Milstein has correlated the yields of but-l-ene and trans-[RhCl(CO)(PMe3 )2] It has also been reported that oct-6-enal can be cyclized to cyclohexanol. 

Yamamoto et al. [42] reported a highly enantioselective ene cyclization with a chiral zinc reagent as Lewis acid catalyst. Cyclization of 3-methylcitronellal 57 by at least 3 equiv. catalyst prepared in-situ from (i )-l,T-bi-2-naphthol (BINOL) 58 and Mc2Zn afforded the frans-cyclohexanol 59 in 86 % yield with 88 % ee as the sole product (Sch. 23). Reducing the amounts of the chiral zinc catalyst reduced both the chemical yield and the enantioselectivity. 

When l-(buten-3-yl)cyclohexanol and l-(penten-4-yl)cyclohexanol are treated with chromium trioxide in acetic acid and acetic anhydride, oxidation at the double bonds results in the formation of carbi xylic acids, which cyclize to form 7- and 8-lactones, respectively [5(55], The same reaction occurs with the cycloheptanol analogues in better yields (equation 282) [56S]. 

Adipic acid may be obtained from cyclohexanol by oxidation with hot nitric acid. Cyclohexanol is prepared from phenol by hydrogenation. Thus the entire series of reactions represents (a) the change of an aromatic six-carbon compound to an alicyclic one (6) the opening of a six-carbon ring to an open chain compound (c) the cyclization of an open chain compound. The object of the present experiment is to illustrate this last step through the preparation of cyclopentanone from adipic acid. 

Tin hydride-mediated radical cyclizations onto a C-0 double bond, coupled with subsequent oxidation, can be applied to ketone synthesis. Fraiser-Reid and co-workers demonstrated that the radical cyclization onto an aldehyde carbonyl group is particularly useful for the construction of cyclohexanol derivatives [35]. Examples shown in Scheme 4-17 well feature the cyclization. As Beckwith s kinetic work predicts (Scheme 4-18) [36], when this method is applied to a five-membered ring system, the rapid ring opening hinders the formation of cyclopen-tanols. Accordingly, only cyclohexanols can be reliably prepared using this approach. 

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