Electron poor imines

Fig. 41 Mechanistic proposal for highly electron-poor imines...

Further studies revealed that a 10 mol% loading of AgOTf was sufficient to catalyze the reaction of Danishefsky s diene (195) with a variety of aromatic phenylimines bearing electron-withdrawing/donating substituents, in 57-92% yield within 2-3 h. These studies were carried out in water. Electron-poor imines generally required the use of 3 equiv of diene 195 to obtain satisfactory yields. The method was extended to a one-pot three-component protocol with in situ formation of the imine from the aniline and 1.5 equiv of the aldehyde (Scheme 2.51, Table 2.13). Because of... 

The chloromethyl imines lOa-lOi were employed as representatives of derivatives with a potentially reactive group in the side chain. Their reduction afforded the corresponding amines in >90% ee (Table 4.6, entries 1 9). The resulting amino chlorides were then cyclized to the corresponding aziridines on treatment with t BuO K with retention of the stereochemical integrity [ 12d]. It is pertinent to note that the preparation ofthe sensitive chloro imines lOa-lOi from the a chloro ketones was not entirely free of problems while the electron neutral and electron poor imines lOa-lOc were synthesized and isolated as individual substances, their electron rich counterparts lOg and lOh could not be obtained as pure compounds, since the reaction did not proceed to completion. Therefore, in the latter instances, the imines were generated in situ [12d]. 

Scheme 6.12 Asymmetric hydrogenation of electron poor imines.

The role of acid in influencing the cyclization of 14 with imines towards imidazolines products is at present unclear. One possibility is suggested by the work of Ferraccioli and Croce (16), who have shown that the electronic nature of the imine can have a significant influence upon its reactivity with Munchnone. In particular, while N-alkyl substituted imines react with Munchnones to form (3-lactams, more electron poor imines, such as the N-tosyl substituted substrates, have been found to undergo a 1,3-dipolar cyclization with 14 to form imidazoles. (16) In our case, the role of acid may be in protonation of the imine substrate, thereby creating a more electrophilic C=N which can undergo a dipolar cycloaddition with 14 (path A, Scheme 2). Subsequent heterolysis of the C-0 bond in 18, would yield the observed imidazoline-carboxylate 17. 

As synthetic chemists desired to tune the optoelectronic and redox properties of conjugated polymers in a fine manner, more complicated conjugated systems were required. The two fused heterocycles-substituted polythiophenes 16 and 17 (Chapter 18) illustrate this as electron-poor imine functionality in 16 brings donor-acceptor character to the material, while the more electron-rich thio-based system 17 provides for especially easy oxidation. Polymerization of these complicated bis-2-thienyl monomers by electrochemical methods paves the way for fundamental structure-property relationships to be understood, ultimately directing the synthetic chemist towards soluble polymers (Chart 1.6). 

Kerr reported that Yb(OTf)3 was the most efficient Lewis acid to catalyze the cycloaddition reaction. Although reports by Tang and coworkers showed that scandium triflate was able to catalyze the reaction with an increase in diastereo-selectivity and a lower catalyst loading [42]. In these examples the imines were synthesized prior to the reaction via a condensation between amines and aldehydes. The results showed that both electron-rich and electron-poor imines were successful in the cycloaddition reaction. The position of the substiment on the aryl groups affected the yield obtained, where the para-substituted imines were favored over the artfia-substituted imines as a result of steric interactions. 

One of the earliest reported thermal reactions of Fischer carbene complexes was the reaction with olefins to give cyclopropanes [127]. More recently it has been shown that photolysis accelerates inter molecular cydopropanation of electron-poor alkenes [128]. Photolysis of Group 6 imine carbenes with alkenes... 

Triphenylthieno[3,4-c]pyrazole (414) can be presented as a hybrid of dipolar-contributing azomethine imine ylide (415) or thiocarbonyl ylide canonical forms 416. Upon reacting this ylide with electron-poor olefins, it behaved like a thiocarbonyl ylide. Thus, with maleimide, a mixture of endo (419) and exo adducts (420) were obtained (74JA4276), which resulted from addition at the thiocarbonyl moiety. The reaction of 414 with dimethyl acetylenedicarboxylate gives the desulfurized indazole 418 in addition to the adduct 417 (Scheme 41). 

Later in 2007, Gong utilized If and saturated derivative 2 in a direct Mannich reaction between in situ generated N-aryl imines and cyclic ketones as well aromatic ketones (Scheme 5.3) [10], It was found that electron poor anilines as coupling partners gave the highest enantioselectivities. The authors postulate that acid promoted enolization of the ketone forms the reactive enol which adds to the protonated aldimine. 

The use of lithium amides to metalate the a-position of the N-substituent of imines generates 2-azaallyl anions, typically stabilized by two or three aryl groups (Scheme 11.2) (48-62), a process pioneered by Kauffmann in 1970 (49). Although these reactive anionic species may be regarded as N-lithiated azomethine ylides if the lithium metal is covalently bonded to the imine nitrogen, they have consistently been discussed as 2-azaallyl anions. Their cyclization reactions are characterized by their enhanced reactivity toward relatively unactivated alkenes such as ethene, styrenes, stilbenes, acenaphtylene, 1,3-butadienes, diphenylacetylene, and related derivatives. Accordingly, these cycloaddition reactions are called anionic [3+2] cycloadditions. Reactions with the electron-poor alkenes are rare (54,57). Such reactivity makes a striking contrast with that of N-metalated azomethine ylides, which will be discussed below (Section 11.1.4). 

A simple preparation of electron-poor 2-azadienes and the preliminary study of their ability to participate in [4 + 2] cycloadditions was done almost simultaneously by out group (87CC1195) (Scheme 49). The preparation of 2-azadienes 212 with two appended methoxycarbonyl groups was achieved, in a multigram scale and in nearly quantitative yield, by the insertion reaction of N- trimethylsilyl imines 210 into the carbon—carbon triple bond of dimethyl acetylenedicarboxylate to give 211 followed by protodesilylation with CsF/MeOH. Azadienes 212 underwent at room temperature inverse-electron demand [4 + 2] cycloaddition with cyclic enamines to give exclusively exo-cycloadducts 213 in 82-95% yield. Acid hydrolysis of them resulted in their aromatization to yield 2-pyrindine (n = 1] and isoquinoline (n = 2) derivatives 214. 

Imines derived from aniline and glyoxylic acid esters can be regarded as electron-poor 2-azadienes, in which an aromatic carbon—carbon double bond takes part of the diene system. In this context, Prato and Scorrano et al. were able to achieve the [4 + 2] cycloaddition of ethyl N-phenyl glyoxylate imines with dihydrofuran and indene leading to hexahydrof-uro[3,2-c]- and tetrahydro-7//-indeno[2,l-c]quinolines, respectively, in moderate to good yields (88JHC1831). Similarly, tetrahydroquinoline derivatives were formed by [4 + 2] cycloaddition of 1,2-bis(trimethylsily-... 

The addition of diazoalkanes to alkenes and alkynes has been shown to be a HOMOdiazoalkane-LUMOdipo,arophi,e controlled reaction,5153 and because the orbital energies of imines are comparable to those of electron-poor olefins, the reactivity of diazoalkanes toward imines may also be considered a HOMOdiazoalkane-LUMOimine favored interaction.338... 

The diazoacetonitrile-imine reaction may be considered complimentary to azide addition to cinnamonitriles because in the latter case only triazoline thermolysis products result.284 The reversed order of reactivity of the diazoacetonitrile to that of diazomethane implies an electrophilic attack on the imine and is explained in terms of a LUMOdi MC lonit[ile-HOMOin,int controlled interaction. Thus electron-rich enamines, which do not react with diazoalkanes, may be expected to react with electron-poor diazo compounds. 

The experimental study was carried out with two different imines a standard one, n-hesanaldimine, and an electron-poor one, n-butyl glyoxylate imine. The Scheme 34 shows that the formation of the (3-lactam occurred only when the glyoxylate imime and BF3-Et20 reacted with (trimethylsilyl)ketene. 

Michael-aldol reaction as an alternative to the Morita-Baylis-Hillman reaction 14 recent results in conjugate addition of nitroalkanes to electron-poor alkenes 15 asymmetric cyclopropanation of chiral (l-phosphoryl)vinyl sulfoxides 16 synthetic methodology using tertiary phosphines as nucleophilic catalysts in combination with allenoates or 2-alkynoates 17 recent advances in the transition metal-catalysed asymmetric hydrosilylation of ketones, imines, and electrophilic C=C bonds 18 Michael additions catalysed by transition metals and lanthanide species 19 recent progress in asymmetric organocatalysis, including the aldol reaction, Mannich reaction, Michael addition, cycloadditions, allylation, epoxidation, and phase-transfer catalysis 20 and nucleophilic phosphine organocatalysis.21... 

Electron-poor nitriles react with compound 87 and its derivatives to form the 5-amino-l,2,4-thiadiazole derivatives 104 <1985JOC1295>. Therefore, the formation of product 94 (see Scheme 21) may be explained alternatively by the addition of amidonitrile 93 to compound 90. The mechanism of the formation of product 104 was discussed in detail in CHEC-II(1996) <1996CHEC-II(4)691> but most probably the steps involved are (1) reaction of the electrophilic nitrile with the exocyclic nitrogen of compound 87 or its derivatives (2) loss of nitrogen similarly to the previous reactions and formation of an imine 103 (3) masked 1,3-dipolar cycloaddition/elimination reaction of the nitrile to the imine 103. Since the same nitrile is expelled in the elimination step, only 1 equiv of reagent is needed (Scheme 24). 

The reaction with 1-azabutadiene is also unfavorable for other reasons. To begin with, the 4 + 2 cyclization is inherently less exothermic than with 2-azabutadiene (see Exercise 20, p. 123). Furthermore, the enamine product will rapidly undergo side-reactions with adventitious electrophiles. An imine-enamine tautomerism which transforms R-N=CH-CH=CH-CH3 into RNH-CH=CH-CH=CH2 also contributes to lowering the yield. Finally, electron-poor dienophiles may undergo a competing reaction with the nitrogen lone pair. 

Aminophosphine 4 has been reported to effect the coupling of benzophenone imine and an electron-poor aryl chloride, Eq. (129) [42a]. Hartwig also reported that the system derived from heterocycle 17 is sufficiently reactive to effect a similar transformation [76]. 

The intermediate carbon radical can be trapped by an appropriate electron-poor alkene27. Thus, slow addition (4-5 h) of tributylstannane and a catalytic amount of 2,2 -azobisisobuty-ronitrile to a solution of the /V-phcnylthio imine and methyl acrylate or di-ferf-butyl malonate (5 equivalents) in refluxing cyclohexane gives the cyclization-addition product with satisfactory to good yield but with modest stereoselectivity. 

A variety of compounds may undergo cycloaddition at the C=C bond of vinylidenephosphoranes yielding exocyclic ylides. [2 -(- 2] Cycloadditions of Af-phenyliminovinylidenetriphenylphosphorane to electron poor double bonds of alkenes and imines lead to the formation of four-membered ylides (equation 112). ° ... 

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