Asymmetric cyclohexene oxide

Zinc catalysts for asymmetric cyclohexene oxide/COa copolymerization 172... 

Asymmetric ring-opening of saturated epoxides by organoctiprates has been studied, hut only low enantioselectivities f -c 1596 ee) have so far been obtained [49, 50]. Muller et al., for example, have reported that tlie reaction between cyclohexene oxide and MeMgBr, catalyzed by 1096 of a chiral Schiffhase copper complex, gave froiis-2-metliylcyclohexanol in 5096 yield and with 1096 ee [50]. 

An alternative method for generating enriched 1,2-diols from meso-epoxides consists of asymmetric copolymerization with carbon dioxide. Nozaki demonstrated that a zinc complex formed in situ from diethylzinc and diphenylprolinol catalyzed the copolymerization with cyclohexene oxide in high yield. Alkaline hydrolysis of the isotactic polymer then liberated the trans diol in 94% yield and 70% ee (Scheme 7.20) [40]. Coates later found that other zinc complexes such as 12 are also effective in forming isotactic polymers [41-42]. 

By studying the NMR spectra of the products, Jensen and co-workers were able to establish that the alkylation of (the presumed) [Co (DMG)2py] in methanol by cyclohexene oxide and by various substituted cyclohexyl bromides and tosylates occurred primarily with inversion of configuration at carbon i.e., by an 8 2 mechanism. A small amount of a second isomer, which must have been formed by another minor pathway, was observed in one case (95). Both the alkylation of [Co (DMG)2py] by asymmetric epoxides 129, 142) and the reduction of epoxides to alcohols by cobalt cyanide complexes 105, 103) show preferential formation of one isomer. In addition, the ratio of ketone to alcohol obtained in the reaction of epoxides with [Co(CN)5H] increases with pH and this has been ascribed to differing reactions with the hydride (reduction to alcohol) and Co(I) (isomerization to ketone) 103) (see also Section VII,C). 

A chiral ethylzinc aminoalkoxide 147, synthesized by the addition of ZnEt2 to (cyclohexene oxide with C02 in almost quantitative yield and with an ee of 49%. This value is somewhat lower than that obtained by the same authors from the in situ generated monomeric form of the catalyst, which furnished product with an ee of 70%.213... 

Table 12. Asymmetric ring opening of cyclohexene oxide with anilines catalyzed by complex 73 under microwave irradiation...

Adolfsson, H. Mobrg, C. (1995) Chiral Lewis acid catalyzed asymmetric nucleophilic ring opening of cyclohexene oxide., Tetrahedron Asymmetry, 6 2023-2031. 

It is also possible to desymmetiize a meso epoxide in the alternating copolymerization. Thus, asymmetric alternating copolymerization of cyclohexene oxide with CO2 catalyzed by a dimeric zinc complex provides a polycarbonate in which the diol unit is optically active with 80% ee. (See Scheme 4.24.)... 

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

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. 

However, there are numerous reported instances of stereocontrol by a site-control mechanism involving chiral metal catalysts. That is, Nozaki and coworkers first illustrated the asymmetric alternating copolymerization of cyclohexene oxide and CO2 employing a chiral zinc catalyst derived from an amino alcohol (Fig. 2a) [13-16]. This was soon followed by studies of Coates and coworkers utilizing an imine-oxazoline zinc catalyst (Fig. 2b) [17]. Both investigations provided isotactic poly(cyclohexene carbonate) (Fig. 3) with enantiomeric excess of approximately 70%. 

From the NMR spectrum of copolymers produced from cyclohexene oxide and carbon dioxide it is difficult to assess low levels of asymmetric induction, i.e., low degrees of desymmetrization in the epoxide ring-opening step. In order to determine the extent of asymmetric induction it is necessary to hydrolyze the copolymer leading to the tra s-cyclohexane-l,2,-diol and examine the enantiomeric excess (4) [22]. Figure 4 shows the NMR spectrum in the carbonate region of atactic copolymer produced from cyclohexene oxide and CO2 using an achiral (salen)CrX catalyst. 

Zrrconium(IV) and hafnium(IV) complexes have also been employed as catalysts for the epoxidation of olefins. The general trend is that with TBHP as oxidant, lower yields of the epoxides are obtained compared to titanium(IV) catalyst and therefore these catalysts will not be discussed iu detail. For example, zirconium(IV) alkoxide catalyzes the epoxidation of cyclohexene with TBHP yielding less than 10% of cyclohexene oxide but 60% of (fert-butylperoxo)cyclohexene °. The zirconium and hafnium alkoxides iu combiuatiou with dicyclohexyltartramide and TBHP have been reported by Yamaguchi and coworkers to catalyze the asymmetric epoxidation of homoallylic alcohols . The most active one was the zirconium catalyst (equation 43), giving the corresponding epoxides in yields of 4-38% and enantiomeric excesses of <5-77%. This catalyst showed the same sense of asymmetric induction as titanium. Also, polymer-attached zirconocene and hafnocene chlorides (polymer-Cp2MCl2, polymer-CpMCls M = Zr, Hf) have been developed and investigated for their catalytic activity in the epoxidation of cyclohexene with TBHP as oxidant, which turned out to be lower than that of the immobilized titanocene chlorides . ... 

Mirkin and coworkers reported on catalytic molecular tweezers used in the asymmetric ring opening of cyclohexene oxide. In this case the early transition metal is the catalyst and rhodium functions as the structural inductor metal. The catalyst consists of two chromium salen complexes, the reaction is known to be bimetallic, and a switchable rhodium complex, using carbon monoxide as the switch. Indeed, when the salens are forced in dose proximity in the absence of CO the rate is twice as high and the effect is reversible [77]. 

The efficiency of a new chiral non-racemic and C2-symmetric 2,2-bipyridyl ligand (6) in copper(I)-catalysed asymmetric allylic oxidation reactions of the cyclic alkenes with f-butyl peroxybenzoate has been evaluated. On performing the reaction of cyclopentene, cyclohexene, and cycloheptene in acetonitrile the corresponding product, (lS)-cycloalk-2-enyl benzoate, was isolated in up to 69% yield and in 91% ee 29... 

Bruns and Haufe have described the first examples of a transition metal complex mediated asymmetric ring opening (ARO) of both meso- and racemic epoxides via formal hydro-fluorination [23]. Initial attempts with chiral Euln complexes led to very low asymmetric induction. Opening of cyclohexene oxide 30 with potassium hydrogendifluoride in the presence of 18-crown-6 and a stoichiometric amount of Jacobsens chiral chromium salen complex 29 [24a] finally yielded two products 31 and 32 in a 89 11 ratio and 92% combined yield, the desired product 31 being formed with 55% ee. Limiting 29 to a catalytic amount of 10 mol% led to an increase in the ratio of 31, however, with the enantiomeric excess dropping to 11% (Scheme 5). 

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). 

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. ... 

The first attempt at enantioselective ring opening of meso-epoxides by using a chiral selenolate was reported in 1988 [90]. Enantiomerically pure seleno-binaphthyl compounds 65-67 were synthesized and applied to the asymmetric ring opening of cyclohexene oxide (Scheme 47). 

Among DASF derivatives examined, the compound 32 prepared from the diselenide 2 and cyclohexene oxide was revealed to be the best catalyst for this addition, giving up to 94 % ee. It is noteworthy that the sulfur (33) and tellurium analogues (34) of 32 also catalyzed the reaction to afford the alcohol, but with lower enantioselectivity (52% and 46% ee, respectively). Related compounds 35 and 36 do not act at all as a catalyst for the reaction, indicating that the presence of both hydroxyl and dimethylamino groups in 32 are indispensable to act as an efficient asymmetric catalyst. Typical results of enantioselective addition of diethylzinc to aldehydes other than benzaldehyde catalyzed by 32 are also summarized in Table 4. 

Emziane, M., Sutowardoyo, K. I., Sinou, D. Asymmetric ring-opening of cyclohexene oxide with trimethylsilyl azide in the presence of titanium isopropoxide/chiral ligand. J. Organomet. Chem. 1988, 346, C7-C10. 

C. Anaya de Parrodi, E. Juaristi, Chiral 1,2-amino alcohols and 1,2-diamines derived from cyclohexene oxide Recent applications in asymmetric synthesis, Synlett (2006) 2699. 

Cyclohexene oxide 236 is opened with benzoic acid catalysed by 2.5% of the cobalt salen complex 235 to give the asymmetric half ester 237. Although the ee is only 75% this is improved by recrystallisation to 98% ee. Epoxides on other ring sizes can also be opened enantioselectively. 

The asymmetric sulfide oxidation described in Scheme 2 has a (-)-NLE until eeaux=70% [5]. The (S)-proline catalyzed cyclization of a triketone shows a weak asymmetric depletion [5], as does allylic oxidation of cyclohexene in the presence of a catalyst prepared from Cu(OAc)2 and (S)-proline [41]. 

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