Epoxides nitrogen nucleophiles

One of the most well used methods for the synthesis of aziridines involves a two (or sometimes more) step process in which an epoxide is opened by a nitrogen nucleophile. The resulting P-amino alcohol (e.g. 79) is then converted to an aziridine via a number of different processes. This method is generally not broadly applicable when a variety of different groups on the nitrogen of the aziridine are desired. A useful method to convert an epoxide to a number of different /V-sulfonyl aziridines (e.g. 80) has been reported <06S425>. Simple addition of a sulfonamide to an epoxide provides high yields of 79 which is readily closed to form the aziridine. 

A rather complex microwave-assisted ring-opening of chiral difluorinated epoxy-cyclooctenones has been studied by Percy and coworkers (Scheme 6.131) [265]. The epoxide resisted conventional hydrolysis, but reacted smoothly in basic aqueous media (ammonia or N-methylimidazole) under microwave irradiation at 100 °C for 10 min to afford unique hemiacetals and hemiaminals in good yields. Other nitrogen nucleophiles, such as sodium azide or imidazole, failed to trigger the reaction. The reaction with sodium hydroxide led to much poorer conversion of the starting material. 

Scheme 8E.28. Asymmetric alkylation of vinyl epoxide with nitrogen nucleophile.

A chiral, nonracemic oxirane, (3 )-2-[(R)-fluoro(phenyl)methyl]oxirane, can react with (chiral) amines under the influence of lithium perchlorate using either heat or microwave irradiation. This reaction sequence provides a material from which the ee of chiral a-branched amines can be determined <2005OL3829>. Guanidines serve as a useful nitrogen nucleophile for the direct conversion of epoxides to aziridines <2004JOC8504>. 

A key step in each synthesis is the opening of an epoxide ring with a nitrogen nucleophile to form a new C - N bond. 

Opening the epoxide with a nitrogen nucleophile makes one isomer. At least the alkene is symmetrical so it doesn t matter which end of the epoxide is attacked by the nucleophile. We have chosen azide ion (N ) as the nucleophile. Ammonia wdll also do as, although it can react repeatedly, it usually behaves itself with epoxides. You were not asked to make both diastereoisomers, so we can stop there. 

In the presence of a palladium catalyst, allyl epoxides (113) react with nitrogen nucleophiles at the al-kenic carbon atom remote from the oxirane ring to give 1,4-adducts (114)." In the absence of a palladium catalyst, azide ion attacks the oxirane ring affording 1,2-adducts (115 Scheme 52 and Table 2)." Vinyl epoxide (116) gave 1,2- and 1,4-azido alcohol in a ratio of 1 1.5 irrespective of the reaction system. " Intramolecular cyclization of vinyl epoxide (117) in the presence of a palladium catalyst afforded isoquinuclidine (118 Scheme 52). ... 

Reaction of epoxides with nitrogen nucleophiles affords a variety of P-hydroxyamines and their equivalents. Comprehensive review articles have been published. In conjunction with the development of diastereoselective and enantioselective syntheses of epoxy alcohols, selective oxirane ring cleavage of 2,3-epoxy alcohols and carboxylates by nitrogen nucleophiles has become a versatile route to various amines and their equivalents. For details, the reader is referred to refs. lOSc and 103d. 

Reactions of chiral allylic boranes with carbonyl compounds Reactions of chiral allyl boranes with imines Asymmetric Addition of Carbon Nucleophiles to Ketones Addition of alkyl lithiums to ketones Asymmetric epoxidation with chiral sulfur ylids Asymmetric Nucleophilic Attack by Chiral Alcohols Deracemisation of arylpropionic acids Deracemisation of a-halo acids Asymmetric Conjugate Addition of Nitrogen Nucleophiles An asymmetric synthesis of thienamycin Asymmetric Protonation... 

Sharpless asymmetric epoxidation (chapter 27) of the allylic alcohol 148 with cumyl hydroperoxide and (+)-di-isopropyl tartrate (DIPT) gave the epoxide 149 in excellent yield and enantiomeric purity. The other enantiomer could be made simply by using the other enantiomer of DIPT. The problem is now how to react the epoxide regiospecifically with a nitrogen nucleophile ... 

Highly enantioselective catalytic desymmetrization of meso-epoxides through nucleophihc ring opening was first effectively demonstrated by Nugent, who found that a zirconium trialkanolamine complex catalyzed the addition of azi-dosilanes to meso-epoxides (Scheme 1) [3]. Azide has been the most widely explored nitrogen nucleophile [4,5,6,7], in part due to its utiHty as an amine sur-... 

Scheme 192. Reaction of Alkenyl Epoxides and Aziridines Producing Heterocycles via Carbon-Heteroatom Bond Formation by (a) Intramolecular Allylation of Oxygen and Nitrogen Nucleophiles and (b) Intermolecular [3 + 2]-Cycloaddition with Heterocumulenes...

Reactions with Nitrogen Nucleophiles. Treatment of an epoxide with one of the diethylaluminium amides [153 = Et, CHjPh, or CH2CH=CH2 ... 

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