Acyl imidates

In 12 the upper face is shielded by the isopropyl group, whereas in 13 the lower face is shielded by the methyl and phenyl groups. As a result, alkylation of the two derivatives gives products of the opposite configuration. The initial alkylation product ratios are typically 95 5 in favor of the major isomer. Since these products are diastereomeric mixtures, they can be separated and purified. Subsequent hydrolysis or alcoholysis provides acids or esters in enantiomerically enriched form. Alternatively, the acyl imides can be reduced to alcohols or aldehydes. The final products can often be obtained in greater than 99% enantiomeric purity. 

A chiral aluminum-salen catalyst gives good enantioselectivity in the addition of cyanide (from TMS-CN) to unsaturated acyl imides.338... 

Scheme 6.69 Products obtained from the 12-catalyzed asymmetric Michael addition of malononitrile, nitromethane, and methyl a-cyanoacetate to N-cinnamoylbenzamide derivatives (acylic imides) and 12-catalyzed derivatization of the Michael adduct.

Bader has described the first preparative route to 1,3,5-triazines containing three different alkyl or aryl substituents (65JOC702). The initial step is the formation of an acyl imidate (162) followed by condensation with an amidine to give the product (Scheme 100). Although mixtures are formed, the method is valuable because such triazines are otherwise very difficult to prepare. Typical examples are given in Table 19. 

Keywords iV-acyl imidate, imidazolidine ketone aminal, microwave irradiation, 2,3-dihydro imidazol[ 1,2-c]pyrimidine... 

A mixture of 1.5 mmol of (V-acyl imidate 1 and 3.9 mmol of imidazolidine ke-tene aminals 2 was placed in a Pyrex glass. Then, the tube was introduced into a Synthewave 420 Prolabo microwave oven. Microwave irradiation was earned out with a suitable power for an appropriate time. The reaction temperature is monitored by a computer coupled with the microwave oven. After, the mixture was... 

Die im Bd.XII/2, S. 849ff., beschriebene Herstellungsmethode fur Phosphorsaure-acyl-imid-trichloride aus Carbonsaure-amiden ist auch an a-Cyan-carbonsaure-amiden verifiziert wordenl04 ... 

Phosphorigsaure-acylamid-diester reagieren mit Chloral197 zu Phosphorsaure-acyl-imid - (2,2-dichlor- inylester)-diestern ... 

Methods of IV-Acylation. Lithiated oxazolidinones add to acid chlorides (eq 7) and mixed anhydrides (eq 8) in high yields to form the derived Af-acyl imides. In the latter case the anhydride may be formed in situ with Trimethylacetyl Chloride, and then condensed with the lithiated oxazoiidinone selectively at the less hindered carbonyl moiety. 

Synthesis of Cyclopropanes. Chiral imide enolates which contain y-halide substituents undergo intramolecular displacement to form cyclopropanes. Halogenation of y,5-unsamrated acyl imides occurs at the y-position in 85% yield with modest stereoinduction. The (Z) sodium enolates of these compounds then cyclize through an intramolecular double stereodifferentiating reaction (eq 61). 

Conversion to the Acid. Hydroxide and peroxide agents saponify acyl imides in excellent yields however, with ster-ically hindered acyl groups endocyclic cleavage may predominate upon treatment with Lithium Hydroxide. Lithium Hydroperoxide, however, is highly selective for the exocyclic carbonyl moiety. 

Conversion to Thioesters. The transformation of A7-acyl imides into thioesters with lithium thiolate reagents proceeds with exceptional selectivity for the exo carbonyl moiety even in exceptionally hindered cases. A recent application of this reaction in a complex setting has been reported (eq 66). This transformation is significant in that the normally reliable peroxide hydrolysis procedure proved to be nonselective. The recently reported high yield reduction of thioesters to aldehydes enhances the utility of these thioester intermediates. 

A passible alternative route to dcacylation would involve the nucleophilic attack of the imidazole nitrogen on the newly formed ester linkage of the postulated acyl interinedi-atc. leading to the formation of the acyl imid i/.ole. The latter is unstable in water, hydrolyzing rapidly to give the product and regenerated active enzyme. 

Likewise, the fused-ring triazoline adducts 112, obtained from 1-methyl-1,2,4-triazolium-4-(acyl)imides and propiolic ester, undergo rupture at the N—N or C—N bond to yield triazole or pyrazole compounds (Scheme 37) (76CPB2568). 

Reaction of indoloquinazoline and anthranilic acids, adsorbed on graphite, led to 61 Reaction of aldehydes, 2-aminopyrimidine and alkyl isocyanide afforded 62. A route to 63 was described by reaction of A-acyl imidates with imidazolidine ketene aminals ... 

A route to 2,3-dihydro imidazo[l,2-c]pyrimidines was described by a reaction of A-acyl imidates 610 with imidazolidine ketene aminals 611 in a focused MW oven without a solvent to give 612 in good yields (60-92%) after 15 min. When X = CN, = Me, and = Et, two attacks were observed and the reaction gave a mixture of two regioisomers 612 (R = Me, R = Et, and R = Et, R = Me) in a ratio 3 1, respectively (Scheme 120). The attack on the carbonyl group was favored with respect to the attack on the imino group (96SC453). 

The ring closure of 2-benzimidazoles 620 with A-acyl imidates 621 as jS-die-lectrophiles without a solvent in open vessels under MWI for 15-30 min led to pyrimido[l,6-u]benzimidazoles 622 in 38-86% yields (Scheme 121). In contrast, no ring closure occurred when compounds 620 (X = COOMe) and 621 (R = R = Me) were heated in toluene with continuous azeotropic elimination of water for 48 h 95% of 620 was recovered unchanged (94TL4563). 

Moreover, Schnyder and Indolese proved that the carbonylation of aryl bromides with primary amides or sulfonamides can lead to asymmetrical aroyl acyl imides. When the reactions were carried out under mild conditions, EtaN was found to be the best base and the desired products were produced in 58-72 % yields (Scheme 2.11) [129]. 

Acyl imidates from carboxylic acid amides C(0)NH C(OAc) = N... 

Evans auxiliaries originally developed for the propionate aldol addition were found to be applicable to a range of a-hetero-substituted acyl imides, illustrated in Scheme 4.52 for the valine-derivatized oxazoUdinones 229, pars pro toto the phenylalanine and ephedrine-derived auxiliaries were also used analogously. The robust method, mostly via the boron but also tin and titanium enolates, tolerates inter alia alkoxy, chloro, bromo, alkylthio, and isothiocyanato substituents in a-position and yields Evans-syn diastereomers 230 in a predictable and reliable way with high stereoselectivity (Scheme 4.52) [117]. It is obvious that the extension from propionates to the cx-heterosubstituted carboxylates made Evans aldol method even more valuable. The individual protocols and apphcations have been treated in several overviews [32, 67d-f]. 

The Michael-aldol cascade reaction of2-mercaptobenzaldehyde with a,/ -unsaturated A-acyl imides (293) (R = alkyl, Ar, hetero-Ar), giving rise to thiochromanes (294), has been attained using the thiourea derivative (295) as a chiral organocatalyst. The key factor here is the presence of the pyrazole moiety as H-bond acceptor, which facilitates the activation and contributes to a better organization of the transition state. 

---