Monoepoxidation of 1, 3-diene

Isomerization of monoepoxides of 1,3-dienes.1 In the presence of this catalyst, monoepoxides of a 1,3-diene isomerize in benzene at 105° to a,p-unsaturated aldehydes or ketones with high (E)-selectivity. 

SELECTIVE MONOEPOXIDATION OF 1,3-DIENES CATALYZED BY TRANSmON-METAL COMPLEXES... 

The chemistry of the selective monoepoxidation of 1,3-dienes is presented. By using transition-metal complexes and a terminal oxidant as e. g. hypochlorite it is possible to perform both regioselective and enantioselective expoxidation of a selected double-bond of the 1,3-diene. This procedure allows c. g. one to perfom regioselective epoxidation of the less-substituted double bond of the 1,3-diene, and, furthemore, to avoid the polymerization of the 1,3-diene which is in contrast to conventional oxidation reagents. The scope of this reaction will be discussed and attempts to understand the oxygen-transfer from an oxo-transition-metal complex intermediate to only one of the double bonds of the 1,3-diene will also be discussed. 

This procedure for stereoselective 1,4-functionalization of 1,3-dienes is based on 1,4-acetoxychlorination,2 and allows the preparation of 1,4-disubstituted 2 cyclohexenes with full stereocontrol of the carbon-carbon bond formation in the 4-position. It is also highly regioselective. Other procedures3 4 for obtaining 4-alkyl-substituted 3-cyclohexenol derivatives use 1,3-cyclohexadiene monoepoxide as starting material. None of the previous methods allow the selective preparation of both stereoisomers as shown here. 

Epoxidation of 1,3-dienes with NaOCl catalyzed by S,S-2 provides only monoepoxides with only moderate enantioselectivity ( 45% ee). In the case of (Z,E)-dienes, epoxidation occurs with high selectivity (10 1) at the (Z)-alkene (equation I). In contrast, high enantioselectivity can be obtained with c s-enynes (equation II). 

An alternative approach for achieving enantiodivergence from aUyHc C—O containing substrates is illustrated in the copper-catalysed reaction of 1,3-diene monoepoxides with dialkylzinc reagents (Scheme 6.22) [42]. For the reaction of rac-98 with dimethylzinc in the presence of the chiral phosphoramidite ligand... 

Pd-catalyzed cyclizations of 1,3-diene monoepoxides have thoroughly been studied due to their powerful applications in the total synthesis of natural products such as steroid precursors, vitamin intermediates, or 3-lactone moieties. For example, diastereo- and re-gioselective cycloisomerization of a diestervinyloxirane leads to the 3-lactonic precursor of Cholestane (Scheme 13). 

Nonconjugated perfluorocyclohepta-l,4-diene is oxidized to the corresponding diepoxide by sodium hypobromite [17] (equation 36), whereas the conjugated- 1,3-diene gives a mixture of 1,2-monoepoxide and bridged 2,3 1,4-diepox-ide [IT] (equation 36). 

Cu(i(-catalyzed kinetic resolutions of racemic, cyclic 1,3-diene monoepoxides through the use of dialkylzinc [123] or trialkylaluminium reagents [124] have re-... 

Buta-1,3-diene (10.101, Fig. 10.24) is a gaseous chemical used heavily in the rubber and plastics industry, the presence of which in the atmosphere is also a concern. Butadiene is suspected of increasing the risks of hematopoietic cancers, and it is classified as a probable human carcinogen. Butadiene must undergo metabolic activation to become toxic the metabolites butadiene monoepoxide (10.102, a chiral compound) and diepoxybutane (10.103, which exists in two enantiomeric and one meso-form) react with nucleic acids and glutathione [160 - 163], as does a further metabolite, 3,4-epoxybutane-l,2-diol (10.105). Interestingly, butadiene monoepoxide is at least tenfold more reactive than diepoxybutane toward nucleic acids or H20. Conjugation between the C=C bond and the oxirane may account for this enhanced reactivity. 

Conjugated perfluorocyclohepta-1,3-dicne gives by the same epoxidation a mixture of monoepoxide 14 and diepoxycyclohcptane 15.74 Dichlorinated perfluorocyclohexa-1,3-diene 16 is selectively epoxidized to 17 by trifluoroperacetic acid in 22% yield.107 A bicyclic diene, synthesized from perfluorobenzene and 1,2-dichloroethene, is monoepoxidized to give 18 by the same oxidizing agent in 20% yield.108... 

The effects created by these functionalities are, surprisingly, capable of being transmitted from positions even more remote to the allyl ligand. 1,3-Diene monoepoxides, for example, selectively undergo the addition of nucleophiles remote from the incipient hydroxymethyl group (equation 220).410 4 3 Nitro 414 malonate415 and acetoxy416,417 functionalities show similar tendencies (equations 221-223). Tri-... 

Reaction of RCHO with 1,3-diene monoepoxides.4 The monoepoxides of butadiene or of isoprene after treatment with CrCl2 and 1A1 (2 l) react with aldehydes to form cis-l,3-diols with a quaternary center at C2. 

An unusual syn addition to epoxides occurs when 1,3-diene monoepoxides are treated with organozinc reagents. Thus, the cyclic vinyl epoxide 72 was converted to the cis-ethyl-cyclohexenol 75 with diethyl zinc in methylene chloride and trifluoroacetic acid. The syn addition is believed to derive from an initial coordination of the oxiranyl oxygen to the organozinc compound, which then delivers the alkyl group to the same face. This transfer is facilitated by a relaxation of the sp3 hybridization brought about by the Lewis acidic zinc center and the allylic character of the incipient carbocation <020L905>. 

An example that used this protocol the substrate of which contains a sensitive functionality is depicted in Scheme 45 [202]. 1,3-Diene monoepoxide is easily attacked by a palladium(O) complex to form the corresponding 7r-allylpalladium species. Thus such a process could be banished from the desired selective transformation as depicted in Scheme 46 by the employment of the alkynyltin reagent with an aid of triphenylarsine ligand [203]. Organotin protocol is also convenient for introduction of a small alkynyl moiety such as C2 or C3 or preparation of symmetrical diarylethynes (Scheme 47) [204]. Shirakawa et al. reported recently that iminophosphine 4 is much more effective ligand for palladium than tris(2-furyl)phosphine in this reaction (Scheme 48) [32,205]. 

The third type is common to monoepoxides of cyclic 1,3-dienes In five- to eight-membered rings and results in rearrangement to /3,y-unsaturated ketones in 55-80% yield. This isomerization can be utilized as one step in a route to 4-hydroxy-2-cycloenones. An example is a synthesis of 4-hydroxy-2-cyclopentenone formulated in equation (III). 

Xue et al. have found that otganozinc reagents (ZnEt2, ZnPh2) react with cyclic 1,3-diene monoepoxides in the presence of CF3COOH to give the s-addition products (Scheme 34) <20020L905>. 

Lactones from dienes. Several 1,3-dienes have been converted into lactones by monoepoxidation and conversion to iron complexes with Fe(CO)j with insertion of CO. The lactone is obtained on oxidation with CAN. ... 

Monoepoxides of simple cyclic 1,3-dienes are smoothly converted in good yield to /3,y-unsaturated ketones in the presence of Pd(Ph3P)4 catalyst (eq 47). Other vinyl epoxides, such as those in open chains or in cyclic systems in which the double bond is not in the ring, are converted under similar conditions into dienols. 

Aq. NaN3 and a soln. of startg. vinyl epoxide in THF successively added dropwise with stirring under N2 to a little Pd(PPh3)4 in the same solvent, and stirred at room temp, for 5-10 min - product. Y 75% synsantil 1). Cyclic 1,3-diene monoepoxides failed to react there was moderate diastereoselectivity with carbohydrate derivs. F.e.s. A. Tenaglia, B. Waegell, Tetrahedron Letters 29, 4851-4 (1988). 

Monoepoxides derived from simple cyclic 1,3-dienes possessing ordinary ring size (five- to eight-membered ring) give the corresponding /3,y-unsaturated ketones as the sole product as shown in Scheme 4. The reaction of a 12-membered ring epoxide produces a mixture of 3-cyclododecenone and the dienol. The latter is possibly formed from the type B reaction. The Pd(0)-catalyzed reaction of terminal 1,3-diene epoxides affords a,/3-unsaturated aldehydes predominantly (Scheme... 

Dibromo-7-oxabicyclo[4.1.0]heptanes can be obtained by bromination of the respective 7-oxabicyclo[4.1.0]hept-3-ene, the monoepoxide of cyclohcxa-1,4-diene, and when submitted directly to the dehydrohalogenation reaction give products 3 and 4.2 149 150... 

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