Reactions of imines with dienes or alkenes

The imino Diels-Alder reaction is among the most powerful synthetic tools for constructing A-containing six-membered heterocycles, such as pyridines and quinolines [56]. Although Lewis acids often promote these reactions, more than stoichiometric amounts of the acids are required owing to the 

Strong coordination of the acids to nitrogen atoms [56]. We intended to use rare-earth triflates as a catalyst in this reaction. 

In the presence of 10mol% of ytterbium triflate (Yb(OTf)3, a representative lanthanide triflate), AT-benzylideneaniline (4a) was treated with 2-trimethyl-siloxy-4-methoxy-l,3-butadiene (Danishefsky s diene, 5 [57]) in acetonitrile at room temperature. The imino Diels-Alder reaction proceeded smoothly to afford the corresponding tetrahydropyridine derivative in a 93% yield (Table 8.15). The adduct was obtained quantitatively when Sc(OTf)3 was used as a catalyst. Imines 4b and 4c also reacted smoothly with 5 to give the corresponding adducts in high yields. Next, the reaction of 4a with cyclopenta- 

Other examples and effects of lanthanide triflates are shown in Tables 8.16 and 8.17, respectively [59]. A vinyl sulfide, a vinyl ether and a silyl enol ether worked well as dienophiles to afford tetrahydroquinoline derivatives in high yields [60]. Fujiwara et al. reported a similar type of reaction [61]. As for the lanthanide triflates, heavy lanthanides such as Er, Tm and Yb gave better results. 

2 Three-component coupling reactions of aldehydes, amines and 

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As in the case of Diels-Alder reactions, aqueous aza-Diels-Alder reactions are also catalyzed by various Lewis acids such as lanthanide triflates.113 Lanthanide triflate-catalyzed imino Diels-Alder reactions of imines with dienes or alkenes were developed. Three-component aza-Diels-Alder reactions, starting from aldehyde, aniline, and Danishefsky s diene, took place smoothly under the influence of HBL4 in aqueous media to afford dihydro-4-pyridone derivatives in high yields (Eq. 12.46).114... 

Thus, a new type of Lewis acid, lanthanide triflates, is quite effective for the catalytic activation of imines, and has achieved imino Diels-Alder reactions of imines with dienes or alkenes. The unique reactivities of imines which work as both dienophiles and azadienes under certain conditions were also revealed. Three-component coupling reactions between aldehydes, amines, and dienes or alkenes were successfully carried out by using Ln(OTf)3 as catalysts to afford pyridine and quinoline derivatives in high yields. The triflates were stable and kept their activity even in the presence of water and amines. According to these reactions, many substituted pyridines and quinolines can be prepared directly from aldehydes, amines, and dienes or alkenes. A stepwise reaction mechanism in these reactions was suggested from the experimental results. 

Thus, this new type of Lewis acid, the Ln(OTf)3, is quite effective for the catalytic activation of imines, and has achieved aza Diels-Alder reactions of imines with dienes or alkenes. The unique reactivities of imines which work as both dienophiles and azadienes under certain conditions were also revealed. Three-component coupling reactions between... 

The aza-Diels-Alder reaction is an important and versatile tool for the preparation of nitrogen-containing heterocycles present in numerous natural products and drug candidates. It involves the [4 + 2] cycloaddition of either an imine with an electron-rich diene or an azabutadiene with an electron-rich alkene (inverse electron demand). Catalytic asymmetric variants employing not only metal complexes, but also organic molecules were disclosed over the last few years. 

A-Acyl imines of fluoroalkyl ketones react exothermically with kctcncs and under mild conditions with enol ethers and alkenes to fonn [4+2] cycloadducts (Table 9). They also react with dipoles. In contrast to reactions with sulfonyi imines, competitive [2 + 2] or [2 + 1] cycloadditions or additions onto the imine function are not observed. The strong heterodiene properties of A-acyl imines are illustrated by the reactions of methyl 3.3.3-trifluoro-2-(tri-fluoroacetyliniino)propanoate with dienes which al.so provide 1,3-oxazines as the major product. The minor product is the result of [4 + 2] cycloaddition of the diene with the imine function (Table 9. final entry). ... 

The formation of type II aziridines can also be carried out via the formation of two bonds simultaneously. One of the most common is the formation of two C-N bonds (bonds c and e ) to generate the aziridine ring. This quite often takes the form of a nitrene or nitrene equivalent adding to an alkene. Another highly common route that forms two bonds simultaneously is the reaction of a monocyclic azirine with a difunctional molecule such as a diene or dipole to form bonds d and e . A significantly less common route is the formation of bonds c and b through the addition of carbene or carbene equivalent to a cyclic imine. 

In theory, a pyrazole could react towards dienophiles or dipolarophiles as an azadiene (A) or as a 1,3-dipole of the azomethine imine category (B), both situations being identical with regard to the number of 7r-electrons involved (Figure 25) (see also Section 4.02.1.9.1). There is also the possibility that it may react as an alkene (C) or as an imine (D) towards dienes or 1,3-dipoles. In the case of ethenylpyrazoles a final possibility of a Diels-Alder reaction involving an exo- and endo-cyclic double bond must be considered. 

Kobayashi et al. found that lanthanide triflates were excellent catalysts for activation of C-N double bonds —activation by other Lewis acids required more than stoichiometric amounts of the acids. Examples were aza Diels-Alder reactions, the Man-nich-type reaction of A-(a-aminoalkyl)benzotriazoles with silyl enol ethers, the 1,3-dipolar cycloaddition of nitrones to alkenes, the 1,2-cycloaddition of diazoesters to imines, and the nucleophilic addition reactions to imines [24], These reactions are efficiently catalyzed by Yb(OTf)3. The arylimines reacted with Danishefsky s diene to give the dihydropyridones (Eq. 14) [25,26], The arylimines acted as the azadienes when reacted with cyclopentadiene, vinyl ethers or vinyl thioethers, providing the tet-rahydroquinolines (Eq. 15). Silyl enol ethers derived from esters, ketones, and thio-esters reacted with N-(a-aminoalkyl)benzotriazoles to give the /5-amino carbonyl compounds (Eq. 16) [27]. The diastereoselectivity was independent of the geometry of the silyl enol ethers, and favored the anti products. Nitrones, prepared in situ from aldehydes and N-substituted hydroxylamines, added to alkenes to afford isoxazoli-dines (Eq. 17) [28]. Addition of diazoesters to imines afforded CK-aziridines as the major products (Eq. 18) [29]. In all the reactions the imines could be generated in situ and the three-component coupling reactions proceeded smoothly in one pot. 

The intennolecular acylpalladation corresponds to the addition of an acyl-palladium bond onto a rr-bond system of another molecule this elementary step can also be referred to as an insertion (Scheme I). This produces another organopalladium complex, which can in principle participate in subsequent propagation or termination reactions. This excludes processes that involve alkoxycarbonylation (R— = R O—) and hydrocarbonyla-tion (R— = H—). This section will focus on nonpolymeric intermolecular reactions of acylpalladium complexes with different 7r-bond systems (alkenes, imines, dienes, and alkynes). 

Compared to the hetero-Diels-Alder reaction of carbonyl compounds and derivatives with dienes, where only a limited number of catalytic and enan-tioselective reactions have been reported, the number of asymmetric hetero-Diels-Alder reactions in which the ketone or imine functionality is part of a heterodiene is much higher. In contrast, there are only a few examples of using a,p-unsaturated aldehydes in inverse hetero-Diels-Alder reactions. In the case of the inverse electron demand hetero-Diels-Alder reaction, the ketone or imine functionality is part of an a,(I-unsaturated system, which reacts in a cycloaddition reaction with an electron-rich alkene. The inverse electron demand hetero-Diels-Alder reaction is primarily controlled by a LUMOdiene-HOMOdienophiie interaction, which can be found, for example, in the reactions... 

Carbonyl-ene reactions of alkenes and glyoxylates were promoted effectively by Yb(OTf)3 [18]. With 20mol% of catalyst loading, desired homoallylic alcohols were obtained in good to high yield (Table 13.7). The reaction with diene gave the mixture of an ene product and a Diels-Alder product. Nakagawa et al reported imino ene reaction between alkenes and imines promoted by Yb(OTf)3-TMSCl (or... 

Addition of an T -allyl-Fp complex to this compound affords an T -aIlyl-Fp-substituted cycloheptatriene system. Two double bonds are involved in an (T -diene)iron complex. The remaining free double bond of the silyl enol ether attacks as a nucleophile at the cationic r -alkene-Fp moiety to form an (Tj -diene)iron complexed cyclopentane annulated cycloheptadienone. Treatment with CAN in methanol under carbon monoxide atmosphere releases the methoxycarbonyl-substituted free ligand (Scheme 4-25). Reaction of the Ti -dienyliumiron intermediate of Scheme 4-25 with an ( , Z)-isomeric mixture of ri -crotyl-Fp proceeds with high diastereoselectivity. Four new stereogenic centers are formed in the course of this formal [3+2] cycloaddition. A hetero [3+2] cycloaddition is also feasible between T -ailyl-Fp complexes and aromatic aldehydes in the presence of zinc chloride or titanium(IV) chloride to provide tetrahydrofuran derivatives (Scheme 4-26). A 1,2-shift of the iron complex fragment occurs in the course of this reaction. Employment of imines affords the corresponding pyrrolidines. ... 

This functional group is known as a nitrone. You could think of it as the N-oxide of an imine. The nitrone gets its four electrons in this way there are two jc electrons in the N=C double bond and the other two come from one of the lone pairs on the oxygen atom. The two-electron component in each of these reactions is an alkene which, in a Diels—Alder reaction, would be called a dienophile. Here it is called a dipolarophlle. Simple alkenes (which are bad dienophiles) are good dipolarophiles and so are electron-deficient alkenes. The difference between dienes and 1,3-dipoles is that dienes are nucleophilic and prefer to use their HOMO in cycloadditions with electron-deficient dienophiles while 1,3-dipoles, as their name implies, are both electrophilic and nucleophilic. They can use either their HOMO or their LUMO depending on whether the dipolarophlle is electron-deficient or electron-rich. 

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