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4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride was isolated and fully characterized.90,93 It is a stable compound that can be stored in the solid state at room temperature for up to a month or for several months in the refrigerator, without detectable decomposition. This reagent combined with carboxylic acid gave an active ester 21 (Scheme 19), and was used as condensing reagent for synthesis of esters and amides.94¨C96 Taddei97 reported the application of DMTMM to the solidphase synthesis of peptides. The yields and purity of the products were high.Recently, Kaminski et al.98 introduced 4-(4,6-dimethoxy- 1,3,5-triazin-2-yl)-4-methylmorpholinium tetrafluoroborate as a more stable reagent than the corresponding DMTMM chloride. The new coupling reagent was used in ester and peptide synthesis, in solution, and in solid-phase synthesis. DMTMM 21 (Scheme 20) can be generated by different protocols mentioned above. This active ester, without isolation was used for many transformation of carboxylic group. Giacomelli et al.99 prepared it using CDMTand applied it to the synthesis of N-methoxy-N-methylamides, commonly named Weinreb amides 22 (Scheme 20), a useful precursor to ketones.100 A variety of these compounds were obtained quantitatively from carboxylic acids, and N-protected amino acids with high yields and purity.DMTMMwas also used for this purpose, but the yields of Weinreb amides were lower. It was reported that active ester 21 (Scheme 20), prepared from DMTMM was reduced by hydrogen and Pt/C as the catalyst to the corresponding aldehyde 23 (Scheme 20) in good yields.101 Required optimization of the solvent, hydrogen pressure, temperature, and time of reduction are disadvantages to this method. Higher hydrogen pressure (5 atm) gave alcohols. Activated esters of aromatic carboxylic acid, and N-Boc or N-Z protected a-amino acids were converted to ketones 25 (Scheme 20) or a-amino ketones by Grignard reagent in the presence of stoichiometric amounts of CuI.102 Bandar and Pandit103 reported the synthesis of 2-oxazolines 26 (Scheme 20) from acyloxy triazine. The active ester was reacted at room temperature with 2-amino-2-methyl-1-propanol giving the desired product with good yields. The same conditions, were used for the selective preparation of monoacylated piperazine derivatives 27 (Scheme 20) with good yields.104 Monoacylation of symmetrical diamines often becomes problematic due to competitive bisacylation. Recently, active ester 21 of formic acid was used for the formylation of amines and a-amino acid esters 28 (Scheme 20). The reaction was conducted under reflux in methylene chloride, or under microwave irradiation to reduce the reaction time from hours to a few minutes. The yields were high, the products pure and no significant racemization of the chiral centers was observed. Based on the reactivity of CC, Kunishima et al.106 published preliminary data about a new immobilized dehydrocondensing reagent in a polymerized form (Fig. 7). This polymer reacts with carboxylic acids, in the presence of a NMM like CDMT or DMTMM, giving active esters, which with amines, gave amides in good yields. |
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qq8489(½ð±Ò+50, ·ÒëEPI+1): 2011-04-20 22:53:23
ringzhu(·ÒëEPI-1): »úÆ÷·Òë ÊÕ»ØEPI 2011-04-21 20:18:38
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