Lewis acids reaction with epoxides

McDonald and coworkers studied a series of tandem endo-selective and stereospecific oxacyclization of polyepoxides by reaction with Lewis acid [92-95]. Polyepoxides, such as 50, can be obtained from the epoxidation of triene 49 with ketone 26 (Scheme 8). This cascade cyclization of polyepoxides provides an efficient method to synthesize substituted polycyclic ether structures, which are present in a number of biologically active marine natural products. 

Reaction of 11 with alkoxides (87IM2161) or epoxides (79JINC1421) leads to formation of (NSOR)3 12, in which the structure of the six-membered ring is retained. Reaction with Lewis acids, and presumably suitable silver salts, can lead to the formation of salts [S3N3C12]X 13, although breakdown to other S/N cations is also known (85MI1). 

Beckett MA, Strickland GC, Holland JR, Sukumar Varma K. A convenient n.m.r. method for the measurement of Lewis acidity at boron centres correlation of reaction rates of Lewis acid initiated epoxide polymerizations with Lewis acidity. Polymer. 1996 37 4629-4631. 

The formation of the primary carbocation can be achieved by treatment of an alkene or an epoxide with a Bronsted or a Lewis add, by elimination of water from an alcohol or an alcohol from an acetal and by readion of enones and imines with Lewis acids. The two latter reactions may also be classified under anionic domino reactions depending on the following steps. 

A more versatile method to use organic polymers in enantioselective catalysis is to employ these as catalytic supports for chiral ligands. This approach has been primarily applied in reactions as asymmetric hydrogenation of prochiral alkenes, asymmetric reduction of ketone and 1,2-additions to carbonyl groups. Later work has included additional studies dealing with Lewis acid-catalyzed Diels-Alder reactions, asymmetric epoxidation, and asymmetric dihydroxylation reactions. Enantioselective catalysis using polymer-supported catalysts is covered rather recently in a review by Bergbreiter [257],... 

Amines usually react with epoxides at the less substituted carbon atom (Scheme4.73) [329, 330], With sterically demanding reaction partners these reactions will often proceed slowly or, as with tetraalkyl epoxides, not at all [252, 331]. Higher reaction rates can be achieved by increasing the concentration of the reactants, by using lithium amides as nucleophiles [332], or by catalysis with Lewis acids [252, 333] or Bronsted acids [334]. Ammonia can also be alkylated by 2,3-dialkyl epoxides (80 °C, 15-60 h [335]). Hydroxymethyl epoxides (but not alkoxymethyl epoxides) can be activated toward nucleophilic attack by amines by use of stoichiometric amounts of Ti(OiPr)4 [336] (third example, Scheme4.73). 

Under acidic reaction conditions the formation of isonitriles can compete efficiently with nitrile formation (Scheme 4.87) [377]. Particularly effective reagents for the formation of isonitriles are mixtures of Me3SiCN with Lewis acids such as Zn(II), Pd(II), or Sn(II) salts. Aluminum-derived Lewis acids with Me3SiCN, on the other hand, mediate the conversion of epoxides into nitriles [378, 379]. 

Treatment of 2,3 Cpoxy-l-amines with Lewis acid induces a rearrangement to aziridinium ions that react efficiently with a nucleophiles to give functionalized hydroxy sulfides or hydroxy amines (Equation 23) <1997SL11>. Under the influence of ethylaluminium chloride, an epoxide tethered to an azide undergoes Lewis acid-assisted cyclization followed by an intramolecular Schmidt reaction and subsequent in situ reduction of the intermediate iminium species upon addition of sodium borohydride (Scheme 8). This protocol was used as a key step in a novel synthesis of indolizidine alkaloids of pharmaceutical interest <20030L583, 2004JOC3093>. 

HCN + EtsAl H+ + [EtsAlCN]-Reactions of epoxides with Lewis acids in the absence of nucleophilic species lead to molecular rearrangements (see Chapter 8). 

The choice of the initiating acid allows the synthesis of constitutionally different cyclohexanes. A 6-endo reaction can also be initiated by regioselective epoxide ring opening with Lewis acids. Monocyclization involving ( )-olefins furnishes acetoxymethyl group are stereoselectively syr 18. 

Epoxide 456 was readily converted to cyclopropane 457 by treatment with La(OTf>3 (Scheme 1.215) [300]. The reaction progressed with Lewis acid-induced epoxide opening followed by a semipinacol rearrangement. 

Despite the greather stability of the lanostane nucleus, it is apparently possible to reverse the protostane- lanostane rearrangement. It has been recently reported that the reaction of the epoxide (317) of dihydroparkeol acetate with Lewis acids affords, protostadienol acetate 318 (45%), presumably by secondary dehydration of protostene-3p,l la-diol... 

Epoxides and aziridines are also capable of electrophilic subsitution of indoles. Indolylmagncsium bromide and cyclohexene oxide react to give 3-(lrans-2-hydroxycyclohexyl)indole[14]. Reaction of indoles with epoxides also occurs in the presence of Lewis acids. For example, indole reacts with methyl 2S,3R-epoxybutanoate at C3 with inversion of configuration[15]. 

The epoxidation is generally conducted in two steps (/) the polyol is added to epichlorohydrin in the presence of a Lewis acid catalyst (stannic chloride, boron triduoride) to produce the chlorohydrin intermediate, and (2) the intermediate is dehydrohalogenated with sodium hydroxide to yield the aliphatic glycidyl ether. A prominent side-reaction is the conversion of aliphatic hydroxyl groups (formed by the initial reaction) into chloromethyl groups by epichlorohydrin. The aliphatic glycidyl ether resins are used as flexibilizers for aromatic resins and as reactive diluents to reduce viscosities in resin systems. 

Titanium-IV compounds with their Lewis acid activity may catalyze an interfering rearrangement of the starting allylic alcohol or the epoxy alcohol formed. In order to avoid such side-reactions, the epoxidation is usually carried out at room temperature or below. 

The use of various heterocyclic additives in the MTO-catalyzed epoxidation has been demonstrated to be of great importance for substrate conversion, as well as for the product selectivity. With regard to selectivity, the role of the additive is obviously to protect the product epoxides from deleterious, acid-catalyzed (Brons-ted or Lewis acid) ring-opening reactions. This can be achieved by direct coordination of the heterocyclic additive to the rhenium metal, thereby significantly decreasing its Lewis acidity. In addition, the basic nature of the additives will increase the pH of the reaction media. 

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