Acyl mesylate

During the total synthesis of the CP molecules, K.C. Nicolaou et al. homologated a sterically hindered carboxylic acid, which was part of an advanced intermediate. Due to the sensitive nature of this intermediate, the diazo ketone was prepared via the acyl mesylate rather than the acid chloride. The diazo ketone then was immediately dissolved in DMF H20 (2 1) and heated to 120 °C in the presence of excess Ag20 for one minute to generate the homologated acid in 35% yield. 

In general, only slight modifications to the Amdt-Eistert homologation have been reported. As mentioned previously, classically two equivalents of diazomethane are required due to the production of HCl upon reaction of diazomethane with the acid chloride. Newmann and Beal reported a modification whereby triethylamine is added to capture the released HCl and therefore only one equivalent of diazomethane is required. Another major source of diversity in the reported Amdt-Eistert reactions is in the initial activation of the carboxylic acid. While thionyl chloride is classically used, other reagents that mediate the eonversion of a earboxylic acid to an acid chloride are equally suitable. As reported above, alternative activation methods such as the formation of mixed anhydrides and acyl mesylates are also be applicable. 

In a similar vein, acylation of the corticoid 50 with furoyl chloride gives the diacyl derivative 51. Reduction with sodium borohydride serves to convert the 11-ketone to the alcohol 52. Hydrolysis under mild acid conditions preferentially removes the acyl group at the less hindered 21 position. The hydroxyl group in that derivative (53) is then converted to the mesylate 54. Replacement by chlorine affords mometasone (55) [12]. 

UV spectra of a variety of 1 -alkyl-1 //-1-benzazepines,20,21 3//-l-benzazepines,20 l-acyl-l//-l-benzazepines,1 3,22,23 3-acyl-3//-3-benzazepines,22-23 3-alkyl-37/-3-benzazepines and their cations in concentrated sulfuric acid,24,25 and 3-mesyl-3//-3-bcnzazepine,2ft have been recorded. A comparison of the UV spectra of 3-alkyl-l, 5-dihydroxy-3//-3-benzazepinc-2,4-dicarboxylates and their bis-O-methyl ethers supports an enol rather than an amide structure for these derivatives.14... 

The mass spectra of l-acyl-l//-l-benzazepines have been recorded.23 The mass spectrum of 3-mesyl-3/7-3-benzazepine shows an intense base peak at m/e = 142duetothebcnzazepinylium ion and a peak (51 %) at m/e — 115 (-HCN) which is attributed to the indenium cation.26 Fragmentation patterns for 1H- and 5/7-2-benzazepines40 and for 5//-dibenz[c,e]azepine5 are available. The electron-impact induced fragmentation pattern of 5//-dibenz[6,/]azepine displays an intense molecular ion as the base peak, and a moderately intense (M + 1) peak.5 ... 

O-Acylated or mesylated oximes such as the ethyl carbonate of acetophenone-oxime 1772 react with TIS 17, with Beckmann rearrangement to the imidoyl iodide 1773, which adds phenylmagnesium bromide in situ to give 61% of the sec-... 

The stereoselective total synthesis of (+)-epiquinamide 301 has been achieved starting from the amino acid L-allysine ethylene acetal, which was converted into piperidine 298 by standard protocols. Allylation of 297 via an. V-acyliminium ion gave 298, which underwent RCM to provide 299 and the quinolizidine 300, with the wrong stereochemistry at the C-l stereocenter. This was corrected by mesylation of the alcohol, followed by Sn2 reaction with sodium azide to give 301, which, upon saponification of the methyl ester and decarboxylation through the Barton procedure followed by reduction and N-acylation, gave the desired natural product (Scheme 66) <20050L4005>. 

Similarly, proximate-parallel bishydrazine 442 can be transferred to 443 by direct acylation with maleic anhydride. Analogous derivative 445 can be obtained from the same starting compound by treatment with methyl 3,4-epoxy-butanoate to provide 444, followed by mesylation and elimination of the intermediate mesylate (Scheme 73) <2005EJ01311>. 

Pankova and Tichy prepared all four stereoisomeric 4-rerr-butyl-2-aminomethyl-l-cyclohexanols and cyclized them with ethyl benzimidate to hexahydro-l,3-benzoxazines 158-161 (74CCC1447). From the A-acyl O-mesylate derivatives 162 and 163 on thermal cyclization or thionyl chloride treatment, ring closure occurred with inversion and resulted in 158 and 159 (74CCC1447). 

The position of the pyranose-furanose equilibria in solution has been determined for the four 5-acetamido-5-deoxypentoses the proportion of the pyranose form (which contains the nitrogen atom in the ring) is — 65% for the xylo, 50% for the lyxo, 25% for the arabino, and 10% for the ribo isomer,124 and this is the order found for the parent pentoses. The corresponding 5-(benzyloxycarbonyl)amino-5-deoxypentoses, however, exist in solution almost exclusively in the pyranose form,130 reflecting the diminished extent of deactivation of the amide nitrogen atom but a solution of 5-(benzyloxycarbonyl)amino-5,6-dideoxy-3-0-mesyl-L-idose was found to contain 20% of the furanose forms, because the steric effect of the N-acyl group forces it into the particularly unfavorable 4Cx(l) conformation (26) of the y3-pyranose form.132... 

---