IV-alkoxycarbonyl

The preparation and spectroscopic properties (infrared, ultraviolet, NMR) of iV-alkoxycarbonyl-N -(2-thiazolyl)thioureas (268) have been studied by the Nagano group (78, 264). These compounds react with bromine in acetic acid or chloroform to give 2--alkoxycarbonylimino-thiazolo[3,2-h]thiadiazolines (Scheme 162), whose structures were established by mass spectroscopy, infrared, NMR, and reactivity patterns (481). 

The 3-nitroindoles show interesting reactivity toward the anion of ethyl isocyanoacetate iV-sulfonyl derivatives give the pyrrolo[3,3-b indole ring system lEq. 10.38. " On the other hand, iV-alkoxycarbonyl derivatives give the normal product, the pyrrolo[3,4-li indole ring system fEq, 10,39, ... 

FIGURE 4.17 Enantiomerization data for reactions of activated IV-alkoxycarbonyl-L-amino acids with an amino acid anion.71,72 Percentage -d-d- peptide formed in reaction with H-d-Val-CL-Na+ in dimethylformamide-water (4 1) at 23°C. 

It is clear from a study of thermal and radical-induced decompositions of N-alkoxycarbonyldihydropyridines that radical processes are of minor importance, and that pyridine formation is probably a consequence of 1,2-elimination of formate (Scheme 6). It has also been concluded that the rate of 1,4-elimination of formate from iV-alkoxycarbonyl-l,4-dihydropyridines at higher temperatures is too rapid to be explained by a homolytic process. 

Al-(Alkoxycarbonyl) 0-(arenesulfonyl)hydroxylamines [alkyl Af-(arenesulfonyloxy) carbamates] 3i-o can be easily obtained by sulfonylation of commercially available iV-(alkoxycarbonyl)hydroxylamines (alkyl V-hydroxy carbamates). Af-(Alkoxycarbonyl) hydroxylamines can be also prepared from hydroxylamine and alkyl chloroformate . ... 

Finally, cationic ring-opening polymerization of 2-aIkoxy-5(4//)-oxazolones has been used to prepare poly iV-alkoxycarbonyl amino acids. The polymerization was found to be dependent on the nature of the amino acid side chain and the substituent on C-2. 

Several iV-alkoxycarbonyl derivatives of 2-amino-2-deoxy-D-glucose have been prepared in this way by reacting D-fructose with the appropriate amino acid.84 The rearrangement is catalyzed by ammonium chloride, and the epimer with the d-gluco configuration is formed preferentially. Such derivatives, when formed from optically active amino acids, are diastereo-isomers, separable by chromatography this observation has been used for the resolution of DL-alanine, since the rearrangement can be reversed, and the amino acid can be recovered by alkaline treatment. 

Oxidation of the iV-alkoxycarbonyl-2-azabicyclo[2.2.0]hex-5-ene 158 with ruthenium tetroxide followed by esterification with diazomethane affords the cis-2,3-diester of azetidine 159 (R = Me) in 67% overall yield. The N-protecting group can be easily removed from the diacid by acidic hydrolysis to give acidic amino acid 160 in 85% yield. Strangely, the 2,3-diester 159 (R = Me) upon acidic hydrolysis failed to give any of the amino acid. This approach to azetidines is useful because 158 is readily available from pyridine in three steps <2003CPB96>. 

Dihydropyridines are far more stable than the previously mentioned dihydropyridine isomers and have been used in numerous synthetic transformations. In particular, iV-alkoxycarbonyl-l,2-dihydropyridines, which can be obtained from the Fowler reduction of pyridines, are widely used. The use of phenyl chloroformate rather than ethyl or benzyl chloroformate in the Fowler reduction of 3-substituted pyridines, where the substituent is an electron-withdrawing group, was found to increase the yield and selectivity of the 3-substituted-l,2-dihydropyridine (Scheme 15) <20010L201>. 

Photoirradiation at 300nm of iV-alkoxycarbonyl-l,2-dihydropyridines results in ring closure and the formation of 2-azabicyclo[2.2.0]hex-5-enes. Substituents are tolerated at the 2-, 3-, and 4-positions however, the yields are significantly lower than those for unsubstituted dihydropyridines. Irradiation of 2-substituted-l,2-dihydropyridines 112 proceeds via a torquoselective process to give only the endo-product 113 (Equation 5) <2001JOC1805, 2000T9227>. 

Enders D, Oberborsch S (2002) Asymmetric Mannich reactions with a-silylated trimethylsilyl enol ethers and IV-alkoxycarbonyl Imines. Synlett 2002 471-473... 

Dihydropyridines have also been starting points for stereospecific syntheses of hydro-phenanthridines and isoquinolines. Interest exists in these compounds because of the occurrence of this structural feature in alkaloids. For example, isoquinuclidine (263), derived from iV-alkoxycarbonyl-l,2-dihydropyridine, undergoes a Cope rearrangement to give the isoquinoline derivative (264) (80JA6157). Further chemical transformations of (264) provided a formal total synthesis of reserpine (Scheme 50). 

Considering the monoaminomercuration-demercuration of 1,4-hexadiene with Af-me-thylaniline leads to Af-methyl-iV-(l-methylpent-3-enyl)aniline, the stereoselective synthesis of iV-alkoxycarbonyl or iV-tosyl cM-2,5-dimelhylpynolidine from the same diene has been explained on the basis of an initial amidomercuration reaction on the terminal bond followed by the second addition of mercury(II) salt to the internal double bond, on the less sterically hindered site (equation 171). 

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