Rearrangement amino esters

Carboxylic acid, 161, also serves as starting material for a substituted pyrazine that has proven to be an important diuretic agent. As the first step in the synthesis the acid is converted to the corresponding amide (165). Treatment with a single equivalent of hypobromous acid effects Hoffmann rearrangement of only one of the amide groups. Ethanolysis of the intermediate carbamate leads directly to the amino ester (166). Exposure of the... 

Only limited precedent exists for the stereoselective enolization and subsequent condensation of a-heteroatom-substituted esters 48a and 48b (eq. [29]). Ireland has examined the enolization process for a-amino ester derivatives where the Claisen rearrangement (chair-preferred transition states) was employed to ascertain enolate geometry (Scheme 10) (43). These results imply that 48a [X = N(CH2Ph)2 ] exhibits only modest selectivity for ( )-enoIate formation under the... 

When the unsaturated Y-benzoyl a-amino ester 443 was treated with MCPBA, the oxirane 444 formed first immediately underwent an intramolecular rearrangement with cleavage of the oxirane ring by attack of the amide oxygen to give a 3 1 mixture of two cis- and /ra r-isomers of 5,6-dihydro-47/-l,3-oxazine derivatives 445 and 446, the configurations of which were determined via their 0-3,5-dinitrobenzoyl derivatives (Scheme 85) <2003M69>. 

Strongly acidic conditions gives the amino alcohol. However, the reaction can be stopped at an intermediate stage if it is carried out under mild conditions. For example, the initially formed amino ester can be isolated or trapped in certain cases although it is more commonly rearranged to the hydroxy amide, typically under mildly basic conditions (Schemes 8.88 and 8.89). The configuration of the oxazoline at the 4 and 5-positions is normally retained under the hydrolysis... 

Aldol products do not have to come from an aldol condensation. In another example of catalysis by a small organic molecule, Jeffrey Bode of UC Santa Barbara reports (J- Am. Chem. Soc. 2004,126, 8126) that the thioazolium salt 7 effects the rearrangement of an epoxy aldehyde such as 6 to the aldol product 8. This is a net oxidation of the aldehyde, and reduction of the epoxide. As epoxy aldehydes such as 6 are readily available by Sharpless asymmetric epoxidation, this should be a general route to enantiomerically-aldol products. The rearrangement also works with an aziridine aldehyde such as 9, to give the ff-amino ester 10. 

A synthesis of a-( trifluoromcthyl)-a-amino esters 5 has been developed based on the [1,2] Stevens rearrangement of nitrogen ylides 4, obtained by the transition-metal-calalyzed decomposition of methyl 2-diazo-3,3,3-trifluoropropanoate (3) in the presence of tertiary amines.2... 

P,y-Unsaturated a-amino esters. y-Phenylseleno-a, (3-unsaturated esters on treatment with NCS (3 equiv.), N,N-diisopropylethylamine (6 equiv.), and an alkyl carbamate (3 equiv.) in methanol at 25° rearrange to derivatives of p,y-unsaturated a-amino acids, generally in 60-80% yield.2... 

More recently, the direct reaction of amines and amino esters with azetidin-2,3-diones 128 at 90°C, Scheme 43, leading to peptides 130, has also been reported. The reaction is believed to occur through formation of an aziridine intermediate 129 which then rearranges to the amino amide with coextrusion [119, 120]. 

The synthesis of novel azetidine derivatives remains the subject of intensive study. New procedures for the preparation of this class of compounds include, e.g., rearrangement of /3,7-aziridino-a-amino esters <2007OL4399>, copper-catalyzed multicomponent reactions of terminal alkynes, sulfonyl azides, and carbodiimides <20070L1585>, regioselective addition of 1,3-dicarbonyl dianions to iV-sulfonyl aldimines <2007T4779>, elaboration of a-amino acids <2007TL2471>, palladium-catalyzed iV-arylation of azetidines <2007S243> and... 

Silver benzoate in methanol is also the catalyst of choice for the classical homologation of cr-amino acids (and peptides) to the corresponding f3-amino esters by Wolff rearrangement.353 An interesting application in natural... 

The pyrazole (224) is readily available from tetracyanoethylene and methylhydrazine. It reacts with refluxing iV-alkylformamides to give the pyrazolopyrimidines (e.g. 225, 62%) after spontaneous Dimroth rearrangement (73JCS(P1)1903). Formamides with amino esters such as (226) give pyrazolopyrimidones (227) (56HCA986). 

Coldham, I., Middleton, M. L., Taylor, P. L. Investigations into the [2,3]-aza-Wittig rearrangement of /V-alkyl /V-allyl a-amino esters. J. Chem. Soc., Perkin Trans. 11998, 2817-2822. 

Rearrangement with chi fluoroalkylamines. 0-Acyla of lb, thereby establishing a a-amino esters from chromium CO insertion, alcoholysis, and r... 

Hence, Claisen rearrangement of / -amino ester 1404 and /i-alkoxy ester 2511 were followed by further transformation. For similar reactions of /i-seleno esters see refs 233 and 512. 

The concept of enantioconvergent synthesis has heretofore been virtually restricted to cases in which the chiral center is directly epimerizable such as in a-amino acids. In an alternative view, the separate transformation of two enantiomers via stereochemical 1y complementary pathways into a single enantiomeric series represents a case of enantioconvergence.(D For example, conversion of the enantiomeric alcohols la and lb to Ic via the Z and olefins respectively converge to the same enantiomer of the product derived via a Claisen ortho ester rearrangement (equation 1). (, 3)... 

---