Cyclopentanol formation

The reaction of nitrous acid with the amino group of the /3-amino alcohol—e.g. 1-aminomethyl-cyclopentanol 1—leads to formation of the nitrosamine 4, from which, through protonation and subsequent loss of water, a diazonium ion species 5 is formed " —similar to a diazotization reaction ... 

In further modifications of these norprogestins, reaction of norethindrone with acetic anhydride in the presence of p-toluene-sulfonic acid, followed by hydrolysis of the first-formed enol acetate, affords norethindrone acetate (41). This in turn affords, on reaction with excess cyclopentanol in the presence of phosphorus pentoxide, the 3-cyclopentyl enol ether (42) the progestational component of Riglovic . Reduction of norethindrone affords the 3,17-diol. The 33-hydroxy compound is the desired product since reactions at 3 do not show nearly the stereoselectivity of those at 17 by virtue of the relative lack of stereo-directing proximate substituents, the formation of the desired isomer is engendered by use of a bulky reducing agent, lithium aluminum-tri-t-butoxide. Acetylation of the 33,173-diol iffords ethynodiol diacetate, one of the most potent oral proves tins (44). ... 

If no y-H atom is available, or if for sterie reasons abstraction of a 6-H atom is facilitated, this latter reaction occurs with formation of a cyclopentanol. A series of such sequences has been used in the synthesis of dodecahedrane 409a,b>. 

Scheme 11.19 Selective formation of functionalized cyclopentanol 63 via electrochemical reduction ofallenic ketone 61 [80],...

Inspection of the results in Table 2 shows that the predominant retention of configuration was observed in the cases of isopropanol, cyclopentanol, and cyclohexanol. These preliminary data may be rationalized in terms of the paraUel formation of two sulfurane intermediates (254 and 255), which are responsible for inversion and retention at sulfur, respectively. The relative stabilities of these inter-... 

The SiCaC reaction of 5-hexyn-l-al 23 gives the corresponding 2-(exo-silymethylene)-l-cyclopentanol 24 in high yield (Scheme 7.11) [20]. The reaction is accelerated by gem-disubstitution for example, the reaction of 3,3-gem-disubstituted 5-hexyn-l-al 23 (X = C(C02Et)2, C(CH20Me)2) is substantially faster and cleaner than the unsubstituted derivative (X=CH2), which is accompanied by a small amount of silylformylation product [21]. It should also be noted that the formation of l-siloxy-2-methylenecyclopentane is not observed, in sharp contrast with the nickel-catalyzed version of this reaction [20]. 

Titanium-catalyzed cyclization/hydrosilylation of 6-hepten-2-one was proposed to occur via / -migratory insertion of the G=G bond into the titanium-carbon bond of the 77 -ketone olefin complex c/iatr-lj to form titanacycle cis-ll] (Scheme 16). cr-Bond metathesis of the Ti-O bond of cis- iij with the Si-H bond of the silane followed by G-H reductive elimination would release the silylated cyclopentanol and regenerate the Ti(0) catalyst. Under stoichiometric conditions, each of the steps that converts the enone to the titanacycle is reversible, leading to selective formation of the more stable m-fused metallacycle." For this reason, the diastereoselective cyclization of 6-hepten-2-one under catalytic conditions was proposed to occur via non-selective, reversible formation of 77 -ketotitanium olefin complexes chair-1) and boat-1), followed by preferential cyclization of chair-1) to form cis-11) (Scheme 16). 

Bishop and Hamer found that acyclic a,/8-unsaturated 1,2-diketones form cyclopentanol derivatives in high yield, while / ,y-unsaturated derivatives form oxetanes by internal cycloaddition.114 Unexpectedly, the y,S-unsatu-rated derivatives also gave oxetanes after an initial migration of the double bond to the /8,y position. The formation of oxetanes such as 38 was observed in the camphorquinone sensitized dimerization of butadiene.115 Photocycloadditions of a-diketones to various olefins have been studied by several groups.116... 

However, the hydroxyl group can easily be converted to water, a better leaving group, and this allows the reaction to proceed. One such conversion involves tosyl chloride, and the formation of a tosylate. For example, cyclopentanol reacts with TsCl to form cyclopentyl tosylate, and the corresponding tosylate is reduced conveniently to cyclopentane. 

In a very elegant way, Eder performed the regioselective reduction of a dione by treatment with excess of Dibal-H, resulting in the formation of a bisaluminium alkoxide that was selectively oxidized under Oppenauer conditions providing a cyclohexenone, while a cyclopentanol remained unchanged.64... 

Molander reported a variant of this sequential process that results in alkenyl transfer.20 For example, treatment of bromide 36 with SmI2-HMPA resulted in the formation of cyclopentanone 37. Subsequent intramolecular ketyl radical addition to the enol ether and collapse of the resultant organosamarium intermediate 38 gave cyclopentanol 39 in good overall yield (Scheme 6.15).20... 

Hypohalites (RO—Hal) are similar to nitrates (see p. 155) in their photochemical behaviour. Ultraviolet irradiation gives an (n,Jt ) excited state that cleaves to form an alkoxy radical and a halogen atom. The radical may undergo alpha-cleavage before recombination with the halogen atom occurs, and this accounts for the formation of 5-iodopentanal (5.69) from the hypoiodite of cyclopentanol such hypoiodites are generated in situ from the alcohol, iodine and mercury(ll) oxide. In open-chain systems the alkoxy radical can... 

The di-Grignard method has also been applied to reactions of disubstituted amino [41,42], phenoxy, and phenylthio esters [42] to provide difunctional cycloalkanols examples include the conversion of esters 53 to cyclopentanols 54 [Eq. (20) 42]. Similarly, lactones can be converted to diols as in the formation of cyclopentanol 56 from lactone 55 [Eq. (21) 43]. 

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