Epoxy amides

A direct application of the ring-opening reaction of an epoxide by a metal enolate amide for the synthesis of a complex molecule can be found in the synthesis of the trisubstituted cyclopentane core of brefeldin A (Scheme 8.35) [68a]. For this purpose, treatment of epoxy amide 137 with excess KH in THF gave a smooth cyclization to amide 138, which was subsequently converted into the natural product. No base/solvent combination that would effect cyclization of the corresponding aldehyde or ester could be found. 

Functional alkoxyamines used as initiators for NMP include 283-287. The functional alkoxyamines can be formed in situ by use of a functional azo compound or peroxide. NMP has been shown to be compatible with hydroxy, epoxy, amide and tertiary amine groups in the initiator. Carboxylic acid groups can cause problems but may be tolerated in some circumstances.106... 

Sulfur ylides are a classic reagent for the conversion of carbonyl compounds to epoxides. Chiral camphor-derived sulfur ylides have been used in the enantioselective synthesis of epoxy-amides <06JA2105>. Reaction of sulfonium salt 12 with an aldehyde and base provides the epoxide 13 in generally excellent yields. While the yield of the reaction was quite good across a variety of R groups, the enantioselectivity was variable. For example benzaldehyde provides 13 (R = Ph) in 97% ee while isobutyraldehyde provides 13 (R = i-Pr) with only 10% ee. These epoxy amides could be converted to a number of epoxide-opened... 

Masakatsu Shibasaki of the University of Tokyo has developed effective procedures for the epoxidation of a,P-unsaturated amides with high . He has now reported (Angew. Chem. Int. Ed. 2004, 43y 317) reagents for the selective reduction of the epoxy amide 9 to either the p-hydroxy amide 10 or the a-hydroxy amide 11. 

Ti(IV) isopropoxide is an effective reagent for promoting regioselective attack by nucleophiles at the 3-position of 2,3-epoxy alcohols [69], 2,3-epoxy acids [70], and 2,3-epoxy amides [70]. It has been proposed that this process involves coordination to the metal center in the bidentate manner shown for a 2,3-epoxy alcohol in structure 44. Such Ti-assisted nucleophilic opening of epoxides is thought to play a role in the in situ reactions leading to 41 and 43. 

The regioselective ring opening of 2,3-epoxy acids can also be achieved (Eqs 269 and 270) [616]. The titanium-promoted reaction always favors C3 opening of the epoxides whereas in the absence of Ti(0-i-Pr)4 the same reaction proceeds with much lower or even reversed regioselectivity. The same tendency was observed for the reaction of 2,3-epoxy amides [616]. 

Epoxy ketones are selectively reduced with lithium naphthalenide or Cp2TiCl in THF/MeOH ° to the (3-hydroxyketone. Other reduction methods can lead to the epoxy alcohol (see p. ). Reduction of epoxy amides with Sml2 in methanol gave the ot-hydroxyamide. ° ... 

The Lewis acid-catalyzed aza-Payne rearrangement was utilized in the total synthesis of ep/-7-deoxypancratistatin by T. Hudlicky and co-workers. The 2,3-aziridino alcohol was treated with f-BuLi, to generate the epoxy amide that was trapped with piperonyl bromide. 

Moran, E.J., and Armstrong, R.W., Highly convergent approach to the synthesis of the epoxy-amide fragment of the azinomycins. Tetrahedron Lett., 32, 3807, 1991. 

This method has attracted little attention but was a key reaction used by Tishler and co-workers in a total synthesis of the antibiotic cerulenin (4), which contains a sensitive 4-keto-2,3-epoxy amide system. Thus the.butenolide 1 undergoes selective epoxidation with sodium hypochlorite in pyridine to give the hydroxy acid a, which lactonizes on warming to the epoxy lactone 2. Ammonolysis followed by oxidation with Collins reagent gives ( )-cerulenin (4). 

However, certain polymers with very low glass transition temperatures (polyurethanes) or glass transition points at both high and low temperature (polybenzimidazole, epoxy-nylon, epoxy-amide) have good retention of both tensile strength and elongation at cryogenic temperatures and are usually the only materials that will work well at these temperatures. 

Among the wide range of substituted epoxides which have been reported are the rather unusual fluorodinitromethyl epoxides (45) and epoxy-amides... 

A modified form of epoxy is known as coal-tar epoxy coating. This consists of a two package epoxy-amide combination with the addition of coal-tar pitch to either the amide or epoxy portion. It is possible to spray this material up to a thickness of 20 (xm. Its chief use is on underground pipes or aboveground structures where high chemical resistance is needed and appearance is not important. 

An interesting example of chiral induction has been reported, involving a highly regioselective differentiation between two identical groups in an acyclic compound that has a prochiral centre. Cyclization of an epoxy-amide has been used in the synthesis of pyrethroid amides. ... 

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