Bicyclic alcohols, oxidation

Oxidative cleavage of bicyclic alcohols. Oxidation of either exo- or endo-norbornanol (1) with 2 equiv. of ceric ammonium nitrate in 50% aqueous acetonitrile at 50° gives three products of oxidative cleavage, 3- and 4-cyclopentene-acetaldehydes (2) and (3) and 3-nitratocyclopentaneacetaldehyde (4).3 Oxidation... 

Secondary bicyclic alcohols are quantitatively oxidized by Jones reagent however rearranged products are obtamed [5f ] (equation 47)... 

Bicyclic alcohols with angular methyl groups (11, 10-11). The reaction of 2,5-dimethylmethylenecyclopentane (1) with acrolein (1 equiv.) and (CH3)2A1C1 involves two sequential ene reactions to give the expected bicyclic alcohol 2 (69%) and in addition the corresponding ketone 3 (12% yield), even in the absence of an oxidant.6 In the presence of 2 equiv. of acrolein, the reaction results in 3 in 60% yield and only 1% of 2. Apparently, the alkoxide precursor to 2 undergoes... 

A slightly modified procedure - oxidation with 100 per cent excess of chromic acid at 0 °C for a short period - is adopted for strained bicyclic alcohols (e.g. the oxidation of ( —)-borneol to ( —)-camphor, Expt 5.87) and gives excellent yields of the corresponding ketones. Cycle ketones which are susceptible to acid-catalysed epimerisation are moreover obtained by this procedure in a high degree of epimeric purity. 

There exists also a synthesis of cyclopentadecanone (VII/81) and ( )-mus-cone, based on a three-carbon annulation of cyclic ketones followed by the regioselective radical cleavage of the zero bridge of the so formed bicyclic system [44], The synthesis of cyclopentadecanone is summarized in Scheme VII/16. The cyclization of VII/78 to the bicyclic alcohol VII/79 proceeds best (94 % yield) with samarium diiodide in the presence of hexamethylphosphoric acid triamide and tetrahydrofuran [45], The oxidative cleavage of VII/79 to the ring expanded product VII/80, was performed by treatment with mercury(II)-oxide and iodine in benzene, followed by irradiation with a 100 Watt high pressure mercury arc. Tributyltinhydride made the de-iodination possible. 

Yields of ketones are, in general, 85-97%. Yields, however, are significantly lower in the case of strained bicyclic alcohols. In this case, a modified procedure is recommended. In this procedure a 100% excess of the oxidant is used and the reaction is carried out at 0° for 15 min. 

A slightly different approach has been utilized for the three-carbon expansion in a system which does not contain a carboalkoxy group. The initial intramolecular addition step is carried out separately with butyllithium or samarium diiodide to give a bicyclic alcohol (Scheme 78). The radical-induced fiag-mentation step is carried out photochemically in the presence of mercury(II) oxide and iodine to provide the expanded iodo ketone. 

Isomerization of cyclooctene oxide. Isomerization of cyclooctene oxide (1) with lithium diethylamide gives the bicyclic alcohol (2) and 3-hydroxycyclooctene (3) in the approximate ratio of 4 1 (2, 247). The abnormal product (2) is obtained only with medium-ring epoxides large-ring epoxides give exclusively allylic alcohols. Sheng1 finds that cyclooctene oxide can be isomerized exclusively to 3-hydroxycyclooctene (3) if... 

Reaction with epoxides [1, 611, after line 2]. The reaction of epoxides of medium-size rings with lithium diethylamide is complicated. Thus m-cyclooctene oxide (I) gives mainly the bicyclic alcohol (2), and tra/i.s-cyclooctene oxide (5) gives mainly the epimeric bicyclic alcohol (6).38 Using deuterium tracer studies, Cope showed that the bicyclic alcohols (2) and (6) arise by loss of a hydrogen atom from an a-... 

Both enantiomers of the alcohol (entry 1) were oxidized with moderate enantiose-lectivities (E = 7) for the (S) enantiomer. For bicyclic alcohols, the position of the hydroxyl group with respect to the methyl group is essential. Only at a relative trans configuration of both substituents significant oxidation occurred. 

A number of non-steroidal unsaturated alcohols have been oxidized using the Oppenauer procedure.2,3 For example, bicyclic alcohol 20 was oxidized to the corresponding... 

Reaction with cyclic epoxides. The reaction of epoxides of medium-size rings with base (lithium di- -alkylamides) has been extensively studied by Cope and by Crandall (1, 610 611 2, 247). Two products are usually obtained an allylic alcohol formed by -elimination and a bicyclic alcohol derived from a carbene intermediate formed by a-elimination. Boeckman has now found that the ciirbcnc pathway is highly favored if n-butyllithium (3 equiv.) is used as base and if (he reaction is conducted at low temperatures, —78 to 25° in the case of cis-eyelooctene oxide (1) and m-cyclodecene oxide. The oxide of cyclododecene,... 

In conclusion, NO -catalyzed aerobic alcohol oxidation is a growing research area and offers the potential for metal-free aerobic oxidation reactions. Applications of nitroxyl/NO -catalyzed oxidation reactions that employ the sterically unhindered bicyclic nitroxyls (e.g., F-AZADO, ABNO, keto-ABNO) are especially effective with a broad range of substrates bearing diverse functional groups, and reactionengineering advances that allow using these reactions in continuous processes should help to enhance reaction efficiency and promote safety. 

The effect of different substitution on this transannular rearrangement was further studied on a range of disubstituted cyclooctene oxides. cis-4,7-Di(t-butyldimethylsilyloxy)-cyclooctene oxide 80 yielded a mixture of bicyclic alcohol 81, and alkene 82 arising from reductive alkylation [Eq. (28)] [61,62]. 

The light induced bromination of B-OMe-9-BBN [17] in presence of water provides cis-bicyclo[3.3.0]octane-l-boronic acid, which readily undergoes oxidation to ds-bicyclo[3.3.0]octan-l-ol in 65% yield, accompanied by cyclooc-tane-1,5-epoxide in 22% yield [18]. B-Me-9-BBN under identical conditions affords only the bicyclic alcohol (Chart 6.28) [19]. 

Yamamoto and coworkers [6] have reinvestigated the work of Jagar and Hesse [7], It is found, for example, that when lithium di-n-butyl-9-BBN is treated with benzyl chloride for 24 h at room temperature, followed by normal alkaline hydrogen peroxide oxidation, it gives quantitative yields of toluene, 1-butanol and bicyclic alcohol (2). Similar studies with cyclohexanone afford a quantitative reduction to cyclohexanol. 

Decarbo>ylation of a-(oo-carbo grallg l)-p-ketoesters (44) by photoinduced electron transfer leads to one-carbon expanded y-ketoesters and bicyclic alcohols.Irradiation of aqueous alkaline solutions of 2-aryloxy- or 2-aryl-acetic acids at 300 nm in the presence of Selectfluor results in fluorodecarboxylation. Decarbojq lation of aliphatic carboxylic acids or iV-(t-buto)ycarbonyl)amino acids by means of oxidative electron transfer using catalytic amounts of photosensitisers leads to free radicals that can by trapped by actylonitrile. ... 

A bicyclic iodoxole oxide 236, the aliphatic analog of IBX, has been prepared by the fluorination of 1,2-iodoxetane 205 (see Section 3.2.9) with xenon difluoride followed by a hydrolysis of the intermediate, non-isolable, difluoride 235 (Scheme 52 2004TL8173). Compound 236 has reactivity similar to IBX and can oxidize alcohols and sulfides to the corresponding carbonyl compounds and sulfoxides, respectively, in good yields under mild reaction conditions. 

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