Cyclohexene oxidative rearrangement

Examination of the reactions of a wide variety of olefins with TTN in methanol (92) has revealed that in the majority of cases oxidative rearrangement is the predominant reaction course (cf. cyclohexene, Scheme 9). Further examples are shown in Scheme 18, and the scope and limitations of this procedure for the oxidative rearrangement of various classes of simple olefins to aldehydes and ketones have been defined. From the experimental point of view these reactions are extremely simple, and most of them are... 

Titanium enolates.1 This Fischer carbene converts epoxides into titanium enolates. In the case of cyclohexene oxide, the product is a titanium enolate of cyclohexanone. But the enolates formed by reaction with 1,2-epoxybutane (equation I) or 2,3-epoxy butane differ from those formed from 2-butanone (Equation II). Apparently the reaction with epoxides does not involve rearrangement to the ketone but complexation of the epoxide oxygen to the metal and transfer of hydrogen from the substrate to the methylene group. 

Nevertheless, whereas the base-promoted isomerization of simple linear oxiranes and cyclohexene oxide occurs via a -deprotonation mechanism, recent denterinm-labeUng experiments demonstrate that the LDA-mediated rearrangement of cyclopentene oxide in nonpolar solvents furnishes the corresponding cyclopentenol through an a-deprotonation route (Scheme 7) . 

As shown in this scheme, the presence of HMPA during the reaction of LDA with cyclohexene oxide yields exclusively the -deprotonation product. This rearrangement is... 

The enantioselective base-promoted rearrangement of oxiranes was achieved by White-sell and Fehnan in 1980. Various homochiral lithium amides were used for the isomerization of cyclohexene oxide with an enantiomeric excess (ee) up to 36% with the employment of 50 in refluxing THF (Scheme 24). 

TABLE 2. Stoichiometric asymmetric rearrangement of cyclohexene oxide using HCLA 54 to 59... 

The origin of the enantiodiscrimination appears to be strongly dependent on the structure of the HCLA employed. For HCLA bases of type A (53 to 56), stereoselectivity has been empirically deduced to arise [in the transition state (TS)] from the difference of energy between the two diastereoisomeric 1/1 HCLA/oxirane complexes TSl and TS2 (Scheme 27). Indeed, the steric repulsions between cyclohexene oxide and the pyrrolidinyl substituents in TS 1 favor TS 2, as proposed by Asami in 1990 for enantioselective rearrangement of cyclohexene oxide by HCLA 53 (Scheme 26) . ... 

The first example of such a process was reported in 1994 by Asami, who noticed that LDA was less reactive than HCLA 53 toward oxirane and thus proposed its use as a co-base in a catalytic cycle . Based upon this seminal result, the system has been extended to other HCLAs and various co-bases have been tested Selected results for the asymmetric rearrangement of cyclohexene oxide mediated by sub-stoichiometric quantities of HCLA are collected in Table 4. 

Hi. Role of additive. There are some reports in the literature of the beneficial effect of powerful donor solvents such as DBU on the reactivity and enantioselectivity of HCLA-mediated oxirane rearrangements for both stoichiometric and catalytic processes. However, this effect is not general (see above) and the role of such additives is still unclear. In one study, the influence of the concentration of DBU on the relationship between the ee s of catalyst and the product for the enantioselective isomerization of cyclohexene oxide mediated by substoichiometric amount of HCLA 56a (20 mol%) in the presence of LDA (2 equiv) has been investigated. At high DBU concentration (6 equiv), the enantiomeric... 

Enantioselective deprotonation.2 The rearrangement of epoxides to allylic alcohols by lithium dialkylamides involves removal of the proton syn to the oxygen.3 When a chiral lithium amide is used with cyclohexene oxide, the optical yield of the resulting allylic alcohol is 3-31%, the highest yield being obtained with 1. 

Lithium amide deprotonation of epoxides is a convenient method for the preparation of allylic alcohols. Since the first deprotonation of an epoxide by a lithium amide performed by Cope and coworkers in 19585, this area has received much attention. The first asymmetric deprotonation was demonstrated by Whitesell and Felman in 19806. They enantioselectively rearranged me.vo-cpoxidcs to allylic alcohols for example, cyclohexene oxide 1 was reacted with chiral bases, e.g. (S,S) 3, in refluxing TFIF to yield optically active (/ )-2-cyclohexenol ((/ )-2) in 36% ee (Scheme 1). 

Inspired by Koga and coworkers successful results14 with chiral bases in deprotonation of ketones (see Section n.B), Singh and coworkers have rearranged cyclohexene oxide... 

Alexakis and coworkers introduced the dilithiated chiral base 13 prepared from C2 symmetric fraws-diaminocyclohexane (Scheme 9)19. Amide 13 rearranged cyclohexene oxide (1) to allylic alcohol (R)-2 in 76% ee. Deprotonation in presence of 1.5 equiv. of LiCl in THF lowered the ee to 55%. When 13 was used to rearrange cyclooctene oxide in benzene, the allylic alcohol was obtained with an increased ee (87%). 

The search for new chiral bases yielding even higher enantioselectivities has resulted in a number of more complex diamines as amide precursors. For example, Asami and coworkers designed the chiral base 14, which in the rearrangement of cyclohexene oxide 1 gave (,S )-cyclohexen-2-ol ((S)-2) in 89% ee (Scheme 10)2°. This result was a significant... 

Another proline-derived chiral base, namely 17, has been reported by Davidsson and coworkers21. It rearranges cyclohexene oxide 1 into (S)-2 in 78% ee (Scheme 12). 

Asymmetric rearrangement of cyclohexene oxide. Cyclohexene oxide is rearranged to (S)-2-cyclohexene-l-ol in 92% ee by the chiral lithium amide (2) prepared from n-butyllithium and 1. Several related (S)-2-(disubstituted aminomethyOpyrrolidines prepared from (S)-proline are almost as stereoselective. ... 

In 1995, Mioskowski and co-workers reported a new carbenoid 1,2-alkyl rearrangement of a-hydroxy-substituted cyclopentene and cyclohexene oxides treatment of such systems with 3 equiv of an organolithium resulted in the formation of two products, as exemplified by the synthesis of dihydrojasmone and its regioisomer 99 (Scheme 44) <1995JA12700>. 

Yamano and Ito have used the SnCl2 mediated regio- and stereoselective rearrangement of a cyclohexene oxide to produce a precursor to the natural products capsanthin and capsombin (Scheme 63) <20070BC3207>. 

Examples of intramolecular trapping of carbonyl ylide dipoles by alkenes have now been reported.These include, for example, the conversion of the oxirane (172) into the tetrahydrofuran (173). Carbonyl ylides have also been prepared by irradiation of 2,3-bis-(p-methoxyphenyl)oxirane in the presence of dicyanoanthracene as electron-transfer sensitizer direct or triplet-sensitized irradiation, however, leads mainly to rearrangement via carbon-oxygen bond cleavage. In contrast, cyclohexene oxide and styrene oxide, on naphthalene-sensitized irradiation in alcohols, undergo solvolysis via oxide anion-radical intermediates. ... 

Japanese authors have made comprehensive investigations of the rearrangements of oxiranes in the presence of solid acids, bases, and salts.The model compounds employed were cyclohexene oxide and 1-methylcyclohexene oxide. The effects of the acidic and basic properties of the catalysts on the selectivity were interpreted on the basis of the products obtained. The main products are carbonyl compounds and allyl alcohol isomers. Rearrangements of limonene oxide over acids and bases were studied on five different types of Al203 similar research has been carried out on 2- and 3-carene oxides, cis- and trans-carvomenthene oxides and a-pinene oxide. ... 

The reaction of S,S,S-(136) with tris-dimethylaminophosphine/PCl3 in CH3CN at 0°C gave the chiral azaphosphatrane (137) in overall 56% yield. Unfortunately (137) did not induce asymmetry in mandelonitrile formed from the catalyzed reaction of Me3SiCN with PhCHO. It was also inefficient in catalyzing the addition of alkyl cyanide to benzaldehyde, and was not sufficiently basic to effect rearrangement of cyclohexene oxide to 2-cyclohexenol. Further experiments with analogues of (137) are promised for future publications. 

The reaction of cyclohexene oxide with MeMgX was reexamined in 1969, in work which clearly established the importance of the halide. Standard conditions (1 h at 80 C) were employed with 1.4 equiv. of the organometallic, to give the yields listed under equation (83). Only minor amounts of the normal displacement product (200) are formed from the chloride and bromide, and none from the iodide. The iodide and bromide give extensive rearrangement, with the bromide being more selective in the sense that product (198) is expected on the basis of stereoelectronic considerations (backside displacement of halide) from the rra/is-halohydrin. The unusual product from this perspective is (199). It must arise either from the c/s-halohydrin or a process which is not subject to the same stereoelectronic controls, e.g. via a carbenium ion. 

Enhanced reactivity associated with a tertiary center appears to be a factor in the observations made by Naqvi et on treatment of 1-methylcyclohexene oxide (229 equation 97) with MgBr . At 0 C, conditions which give only halohydrin with cyclohexene oxide, (229) was converted into the aldehyde (230). Conversely, when (229) was added to a solution of MgBr2 at 60 C, only ketone rearrangement products were isolated. The modest yields prevent mechanistic conclusions. 

Kennedy and Buse used a LiC104-LiC103 eutectic mixture as a molten salt phase in a GLC column at 280 °C for rearrangement of a few model epoxides. Those with tertiary centers gave lower product selectivity than in the typical solution reaction, but the harsher conditions did cause cyclohexene oxide to rearrange, giving cyclopentanecarbaldehyde as the major product. 

The reaction of cyclohexene oxide with LiBr-HMPA in refluxing benzene leads exclusively to cy-clopentanecarbaldehyde, but, like other enolizable aldehydes, the product is not indefinitely stable to the reaction conditions. The rearrangement of 1,2-dimethylcyclohexene oxide, although much slower, gives only the ketone (218) as shown in equation (120). This result is especially difficult to rationalize by any mechanism other than one requiring a bromohydrin intermediate. 

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