Ethanols, 1-heteroaryl

Scheme 4.37 DKRs of 1 -heteroaryl ethanols and benzoin with Shvo s catalyst.

More recently, Shvo s catalyst 1 was used for a DKR protocol of 1-heteroaryl ethanols [79]. The protocol was found applicable to a wide range of this type of substrate. The desired products were obtained in high to excellent enantiomeric excesses (88 to >99% ee) and with moderate to excellent conversions (57-100%). 

Ethyl-4,5-thiazole dicarboxylates (77), R =H, Me, Et, Ph, or heteroaryl, were prepared from diethyl-a-chloro-/3-ketosuccinate (76) and thioamides in boiling ethanol (Scheme 35) (103, 110, 145, 298, 577, 639). 

Rate data are also available for the solvolysis of l-(2-heteroaryl)ethyl acetates in aqueous ethanol. Side-chain reactions such as this, in which a delocalizable positive charge is developed in the transition state, are frequently regarded as analogous to electrophilic aromatic substitution reactions. In solvolysis the relative order of reactivity is tellurienyl> furyl > selenienyl > thienyl whereas in electrophilic substitutions the reactivity sequence is furan > tellurophene > selenophene > thiophene. This discrepancy has been explained in terms of different charge distributions in the transition states of these two classes of reaction (77AHC(21)119>. 

Active methylene nitriles condense with o-substituted aryl and heteroaryl azides in a two-step process to give tricyclic triazolopyrimidines without isolation of the triazole intermediates <85BSB441, 87BSB587). 5-Azido-4-formyltriazoles (758) condense with dimethyl 3-oxopentanedioate and tri-ethylamine in ethanol to give 5-(triazol-l-yl)-4-formyltriazoles (759), which undergo cyclization to... 

The glyoxime dehydration route is compatible with various substituents including not only alkyl, aryl, and heteroaryl but also acyl, carboxyl, and amino groups for example, 3-amino-4-phenylfurazan is formed on heating a-(hydroxyimino)phenylacetamidoxime with sodium acetate in ethanol, and the same compound also results from treatment of benzoyl cyanide with hydroxylamine and sodium acetate in ethanol <87IJC(B)690>. 

Many 1-heteroaryl-1-alkanols are also easily resolved by hydrolase-catalyzed reactions in organic solvents. Thus, some racemic l-(2-pyridyl)-l-alkanols and isoquinonyl-l-ethanols are easily resolved by CALB (Novozym 435) and vinyl acetate in diisopropyl ether to give the acetates 38—44 (Scheme 4.18) [75]. 

C-Heteroaryl-JV-arylhydrazonoyl halides 28a and 30e react with benzo-ylacetonitrile in ethanol in the presence of sodium ethoxide to give 5-phenyl-4-cyanopyrazoles 237a and b, respectively (87JHC1665 88H695 90JPR484). 

With this versatile alkynone synthesis in hand, the application to the pyrimidine synthesis was tested as well. As previously shown, 4-(indol-3-yl)- and4-(7-aza-indol-3-yl)-2-amino pyrimidines 36, which are structurally related to the marine natural products class of meridianins, have displayed a considerable potential as kinase inhibitors [143]. Therefore, upon reacting indolyl (37, X = CH) and 7-aza-indolyl (45, X = N) substituted alkynones or the pyirolyl ynones 46 with an excess of guanidinium hydrochloride and potassium carbonate in 2-methoxy ethanol at 120°C for 12-24 h the heteroaryl substituted 2-amino pyrimidines 47, 48, and 49 were obtained in good to excellent yields (Scheme 29). 

The reaction can be performed in different organic solvents. Currently ethanol seems to be the most common solvent. This method has been employed almost exclusively for the preparation of sodium alkyl-, alkenyl-, aryl-, and heteroaryl tellnrolates. Metallic lithium and sodium can also be used for the reduction of diorganyl ditellurides. 

P-Heteroaryl-substituted ethanols, pyridine 2-ethanols and pyridine 4-... 

The catalytic activity of Shvo s catalyst is mainly because it dissociates into two monomeric ruthenium species in solution under thermal conditions and it can be combined well with various lipases in DKRs. Minidis and colleagues recently employed a combination of this catalyst with Novozym 435 to achieve the DKR of a series of 1-heteroaryl substituted ethanols, such as oxadiazoles, isoxazoles, l//-pyrazole, or 1//-imidazole. In the presence of / -chlorophenyl acetate as the acyl donor, the corresponding acetates were produced in moderate to high yields and excellent enantioselectivities, as shown in Scheme 4.37. In order to prepare novel chiral pincer ligands based on the 6-phenyl-2-amino-methylpyridine and 2-aminomethylbenzo[/j]quinoline scaffolds, Felluga et al. 

Scheme 8.42 Enzymatic DKR of l-heteroaryl substituted ethanols, catalysed with a Backvall s catalyst analogue.

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