Imino derivatives, addition reactions

The main intermediate of the rearrangement may be a nitrilium ion (225) in some cases or an imidate (226) in others. The resulting intermediate reacts with water to produce the amide (218) after tautomerization. If other nucleophiles (Nu ) are present, they can intercept the reactive intermediates (both inter- or intra-molecularly) and several different imino-substituted derivatives (227) can be formed. These rearrangement-addition reactions will be analysed later in this chapter as they can effectively broaden the scope of the Beckmann rearrangement reaction (Sections VI.D.2 and VI.E.2). 

These addition reactions require formation of an imino-cyclohexadiene intermediate (Fig. 13.41). In cases where the ipso substituent is a proton, tautomeriza-tion to form the substituted aniline derivative is fast, and such intermediates have not been isolated. On the other hand, in situations where the nucleophile adds to a substituted ring position, the intermediate can undergo further secondary reactions. For example Novak et al. showed that the 4-biphenylylnitrenium ion reacts with water forming the imine cyclohexadiene intermediate 74, which in turn experiences an acid-catalyzed phenyl shift reaction to 76 via 75 (Fig. 13.42). 

Other imino derivatives arise, as by-products or in side reactions, on heterocyclization. Thus, the treatment of cinnamoyltropolones 75 with hy-droxylamine (Scheme 19) yields, in the case of the 5-nitro derivative, the corresponding isoxazolotroponeoxime (89JHC371). The formation of oximes and several hydrazones from 3-acetyltropolone or its derivatives has also been mentioned (Section II,A,3,c). Moreover, an azine was obtained in addition to quinoxalotropone 213 (Section II,B,2,c) a tropone immonium salt was isolated after an extremely complex diene reaction of an 6-amino-2-azaazuIene (93CB441). 

Related 1,2-additions to imines in the -lactam area employing organocuprates have also met with considerable success. Net substitution reactions, proceeding via intermediate imino derivatives, have been achieved with lithium diallyl- and dialkyl-cuprates on educts such as (105) and (106). When a stereochemical label is present as in (107) and (108), the major products reflect trans addition to imines (109) and (110), respectively (Scheme 18). 

Two more complicated ring-contraction reactions, both yielding 4-amino-3-oxothiadiazoline 1,1-dioxides, are known. Disselnkoetter reported (71GEP1961864) that the reaction of 1,4,3,5-oxathiadiazine 127 with hydrogen cyanide produced imino derivatives 128, which were easily hydrolyzed to the corresponding oxo derivatives 89b by acid treatment (Scheme 49). The course of the reaction may involve addition of cyanide ion, decarboxylation of the resulting carbamic acid, and a nucleophilic attack at the carbonitrile group, as shown in Scheme 49. 

Imino-Diels-Alder reaction [49] containing the coupling of imine and electron-rich alkene gradually became a powerful tool for the synthesis of quinazohne derivatives [50], In Povarov imino-Diels-Alder reaction, aniline and ethyl glyoxalate were chosen as substrates. And two molecules of a-iminoesters, which were obtained from the condensation of aniline and ethyl glyoxalate, were hypothesized to form the direct additive product. Cascade imino-Diels-Alder reaction conducted by Chenetal. [51] (Scheme 13.11) was extended from the Povarov imino-Diels-Alder reaction. In this research, researchers chose the same substrates as in the Povarov imino-Diels-Alder reaction, adopted various kinds of Lewis acids as catalysts, and finally produced quinazoline derivatives. Iron powder was determined as the optimized catalyst with highest yields. 

A wide variety of /3-lactams are available by these routes because of the range of substituents possible in either the ketene or its equivalent substituted acetic acid derivative. Considerable diversity in imine structure is also possible. In addition to simple Schiff bases, imino esters and thioethers, amidines, cyclic imines and conjugated imines such as cinnamy-lidineaniline have found wide application in the synthesis of functionalized /3-lactams. A-Acylhydrazones can be used, but phenylhydrazones and O-alkyloximes do not give /3-lactams. These /3-lactam forming reactions give both cis and /raMS-azetidin-2-ones some control over stereochemistry can, however, be exercised by choice of reactants and conditions. 

The addition of isocyanides and azide to aldehyde-derived enamines has led to tetrazoles (533,536). On the other hand the vinylogous amide of acetoacetic ester and related compounds reacted with aldehydes, isocyanides and acids to give a-acylaminoamides (534). Iminopyrrolidones and imino-thiopyrrolidones were obtained from the addition of cyclohexylisocyanide and isocyanates or isothiocyanates to enamines (535). An interesting method for the formation of organophosphorus compounds is found in the reactions of imonium salts with dialkylphosphites (536). 

It would be reasonable to expect that the decomposition of the N,N-dimethylimino ester chlorides proceeds via a bimolecular mechanism already demonstrated for the thermal decomposition of simple imino ester salts (79). In the carbohydrate series, where an isolated secondary hydroxyl group is involved, such a process would result in chlorodeoxy sugar derivatives with overall inversion of configuration, provided that the approach of the chloride ion is not sterically hindered. Further experiments are in progress in this laboratory utilizing additional model substance to establish the scope and stereochemical course of the chlorination reaction. 

Tin(Il) shows considerable affinity towards nitrogen, therefore is expected to activate the imino group. The diastereoselective addition of tin(II) enolates derived from thioesters 1 to x-imino-esters 2 is reported12. This reaction proceeds smoothly to afford. vi w-/j-amino acid derivatives 3 (d.r. 95 5) in good yields. Lithium, magnesium, and zinc enolates do not react while titanium enolates give the adducts in low yield with preferential formation of the anti-isomer. 

Enolates derived from various imino compounds have been sulfinylated in reactions analogous to those shown by equations (14) and (15). Some representative examples are shown in equations 16-18. Here again, these compounds have been utilized in asymmetric syntheses. Addition of sulfinate ester 19 to a THF suspension of a-lithio-N,N-dimethylhydrazones, derived from readily available hydrazones of aldehydes and ketones, leads to a-sulfinylhydrazones in good yield, e.g. 53 and 54 (equations 16 and 17)85,86. Compounds 53 and 54 were obtained in a 95/5 and 75/25 E/Z ratio, respectively. The epimer ratio of compound 53 was 55/45. Five other examples were reported with various E/Z and epimeric ratios. 

The comparison of a bis(imino)pyridine iron complex and a pyridine bis (oxazoline) iron complex in hydrosilylation reactions is shown in Scheme 24 [73]. Both iron complexes showed efficient activity at 23°C and low to modest enantioselectivites. However, the steric hindered acetophenone derivatives such as 2, 4, 6 -trimethylacetophenone and 4 -ferf-butyl-2, 6 -dimethylacetophenone reacted sluggishly. The yields and enantioselectivities increased slightly when a combination of iron catalyst and B(CeF5)3 as an additive was used. 

The monomeric metaphosphate ion itself commands a fair amount of attention in discussions of metaphosphates. It is postulated as an intermediate of numerous hydrolysis reactions of phosphoric esters 52 S4,S5) and also of phosphorylation reactions S6> kinetic and mechanistic studies demonstrate the plausibility of such an assumption. In addition, the transient formation of ester derivatives of meta-phosphoric acid — in which the double-bonded oxygen can also be replaced by thio and imino — has also been observed they were detected mainly on the basis of the electrophilic nature of the phosphorus. 

Microwave-induced 1,3-dipolar cycloadditions involving azomethine ylides have been widely reported in the literature. Bazureau showed that imidates derived from a-amino esters 120, as potential azomethine ylides, undergo 1,3-dipolar cyclo-additions with imino-alcohols 121 in the absence of solvent under microwave irradiation. This reaction leads to polyfunctionalized 4-yliden-2-imidazolin-5-ones 122 (Scheme 9.36) [87]. 

In contrast, the reaction of acid-catalyzed nucleophilic addition of alcohols to derivatives of AH -imidazol-1 -oxide (219) and (224) leads only to nitronyl nitroxyl (221) and imino nitroxyl (274) radicals (518). 

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