Cyclohexene oxide reaction with amines

Similar conditions have been applied to the ring-opening of meso epoxides using amines. Bismuth triflate catalyzes the reaction of cyclohexene oxide 64 with p-bromoaniline under aqueous conditions to provide the P-aminoalcohol 65 in 84% yield. In this particular case, the water solubility of the starting materials required the use of a micellar solution of sodium dodecyl sulfate (SDS) however, more soluble amines eould be employed in water and bismuth triflate alone <04TL49>. A lanthanide variant has also been reported. Thus, treatment of 64... 

Treatment of the piperidine 74, obtainable from an aminonitrile such as 73, under N-methylation conditions leads to the dimethylamino derivative 75. The carbobenzoxy protecting group is then removed by catalytic hydrogenation. Reaction of the resulting secondary amine 76 with cyclohexene oxide leads to the alkylated trans aminoalcohol. There is thus obtained the anti-arrhythmic agent transcainide (77) [18]. 

The vinyloxirane reaction was later extended to methylidene cyclohexene oxide and to related meso derivatives [53]. The effects of the diastereomeric ligands 42 and 43 (Fig. 8.5), derived from (S)-binaphthol and (S, S)- or (R, R)-feis-phenylethyl-amine respectively, were investigated. In the case of kinetic resolution of racemic methylidene cyclohexane epoxide 45 with Et2Zn, ligand 42 produced better yields, regioselectivity, and enantioselectivity than 43 (Scheme 8.27). 

Reactions between KCH2SiMe3 and cyclohexene or methylcyclohexene gave white solids formulated as 59 or 60. They were characterized by reaction with CHzO and oxidized with (COCl)2, but no structural data have been reported. Reactions with cyclooctene were similar.45 The role of tertiary amine in the metallation of ethene, n-hexene, and a-pinene has been studied.15... 

For the copolymerization of epoxides with cyclic anhydrides and curing of epoxy resins, Lewis bases such as tertiary amines are most frequently used as initiators. In this case, terminal epoxides react with cyclic anhydrides at equimolar ratios. The time dependence of the consumption of epoxide and anhydride is almost the same for curing 35-36> and for model copolymerizations 39,40,45). The reaction is specific 39,40) to at least 99 %. In contrast, the copolymerization with non-terminal epoxides does not exhibit this high specificity, probably because of steric hindrances. The copolymerization of vinylcyclohexene oxide or cyclohexene oxide is specific only to 75-80 % and internal epoxides such as alkylepoxy stearates react with anhydrides only to 60-65 %. On the other hand, in the reaction of epoxy resins with maleic anhydride the consumption of anhydride is faster 65the products are discoloured and the gel is formed at a low anhydride conversion 39). Fischer 39) assumes that the other resonance form of maleic anhydride is involved in the reaction according to Eq. (33). 

Several catalysts have been found for the ring opening of epoxides. For instance, cyclohexene oxide gave an excellent yield of the trans-fi-amino alcohol when treated with either aromatic or aliphatic amines in the presence of a scandium triflate catalyst.21 Aromatic epoxides react in a regiospeciflc reaction at the benzylic carbon when treated with aromatic amines and scandium triflate but at the least substituted carbon of the epoxide ring when aliphatic amines react. Electronic effects are more important in the reactions of the aromatic epoxides whereas steric factors control the reaction with aliphatic epoxides. 

Simple aliphatic oxiranes can be converted to fluorohydrin with hydrogen fluoride only with great difficulty, but the reaction can be carried out in systems with rigid conformations (e.g., steroids, 9,10-epoxydecalin). Good yields can be attained from cyclopentene and cyclohexene oxides with 42% pyridine-polyhydrogen fluoride and in a series of terpene oxides with an amine-hydrogen fluoride complex. ... 

VINYL CYCLOHEXENE or VINYL-l-CYCLOHEXENE (100-40-3) Forms explosive mixture with air (flash point 61°F/16°C). Hydrolyzes in water. Violent reaction with strong oxidizers. Incompatible with alcohols, amines, strong acids, strong alkalis. 

Lithium amides derived from secondary amines like lithium diisopro-pylamide (1) appear to be strong enough bases to deprotonate epoxides, ketones, etc. However, when 1, which is a non-chiral base, deprotonates the non-chiral epoxide cyclohexene oxide (2), equal amounts of the two enantiomeric products (5)- and (/ )-cyclohex-2-enol (3) are formed in the abstraction of a proton from carbon 2 and 5, respectively, with accompanying opening of the epoxide ring (Scheme 1). Thus, none of the two enantiomeric products is formed in enantiomeric excess (ee), i.e., the reaction shows no stereoselectivity (Scheme 1). 

Spiro-linked CMPs functionalized with metal phthalocyanine units show enhanced catalytic activity towards different reactions." The Co-phthalocyanine-incorporated CMP acts as a catalyst with improved activity for cyclohexene oxidation, hydroquinone oxidation and H2O2 decomposition, whereas the spiro-linked Fe-porphyrin network shows increased catalytic activity for hydroquinone oxidation. The spiro linkages in these networks open up a lot of free space around the catalytic sites to enhance the accessibility of substrates to reach more catalytic sites. More functionalization in this vray of conjugated networks by various metals improves the scope of these networks in heterogeneous catalysis. Oxidation of sulfides, reductive aminations and photocatalyzed aza-Heniy reactions are reactions effectively catalyzed by different metal-incorporated CMPs" (Figure 10.6). 

Bismuth is another example of nonrecommended cation by Table 8.1. It is also one of the most investigated metal triflate catalysts in organic reactions. Ollevier and Lavie-Compin used Bi(OTf)3 as catalyst for the Mannich reaction in water [28], Cyclohexene oxide was treated with amines such as p-methylaniline to isolate the corresponding p-amino alcohols in good yields (Equation (8.10)). Sterically more hindered anilines such as o-methylaniline also led to the alcohols in good yield (SDS, sodium dodecyl sulfate). 

The cyclohexene 121, which was readily accessible from the Diels-Alder reaction of methyl hexa-3,5-dienoate and 3,4-methylenedioxy-(3-nitrostyrene (108), served as the starting point for another formal total synthesis of ( )-lycorine (1) (Scheme 11) (113). In the event dissolving metal reduction of 121 with zinc followed by reduction of the intermediate cyclic hydroxamic acid with lithium diethoxyaluminum hydride provided the secondary amine 122. Transformation of 122 to the tetracyclic lactam 123 was achieved by sequential treatment with ethyl chloroformate and Bischler-Napieralski cyclization of the resulting carbamate with phosphorus oxychloride. Since attempts to effect cleanly the direct allylic oxidation of 123 to provide an intermediate suitable for subsequent elaboration to ( )-lycorine (1) were unsuccessful, a stepwise protocol was devised. Namely, addition of phenylselenyl bromide to 123 in acetic acid followed by hydrolysis of the intermediate acetates gave a mixture of two hydroxy se-lenides. Oxidative elimination of phenylselenous acid from the minor product afforded the allylic alcohol 124, whereas the major hydroxy selenide was resistant to oxidation and elimination. When 124 was treated with a small amount of acetic anhydride and sulfuric acid in acetic acid, the main product was the rearranged acetate 67, which had been previously converted to ( )-lycorine (108). 

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