Tandem reactions imines

Hydroaminomethylation is a promising reaction to functionalize unsaturated compounds with an amino group [13, 48, 49], The tandem reaction was discovered by Reppe in 1949 and has been further developed in recent years by Eilbracht and Beller. Hydroaminomethylation consists of three consecutive reactions which are carried out in the same reaction vessel [48], The first reaction is hydroformylation which is followed by the condensation with an amine. Hydrogenation of the generated enamine/imine to the amine is the last step. The conditions for hydroaminomethylation are related to the hydroformylation reaction but are not similar due to the two other reactions. The reaction is called an auto-tandem reaction because two of the three reactions need the same catalyst [9] (Scheme 16). 

The condensation of an imine with a Reformatsky-type reagent and tandem reactions can result in asymmetric induction.3-207-484 87 The reaction of a ketene with an electron-rich alkene results in a [2+2] cycloaddition, although other systems can also be used,488 90 The stereochemistry of the adduct is cis, and functionalized ketenes can also be used. The ketene can be generated in situ (Scheme 26.21).491... 

The tandem reaction of carbenoids with simple imines to form azomethine ylides which then undergo 1,3-dipolar cycloaddition with various dipolarophiles was first reported in 1972.81 Treatment of phenyldiazomethane with copper bronze in the presence of excess N-benzylidenemethylamine resulted in the isolation of imidazoline 170. Formation of this product was rationalized by carbenoid addition onto the imine nitrogen to give azomethine ylide 169 which then underwent a 1,3-dipolar cycloaddition with another molecule of imine to produce the observed product. Bartnik and Mloston subsequently extended this observation by using other dipolarophiles.82 For example, catalytic decomposition of phenyldiazomethane and A-benzylidenemethylamine in the presence of dimethyl maleate or benzaldehyde gave pyrrolidine 171... 

Addition to imines. In the presence of LiC104, w-bromonitriles are attacked by Grignard reagents to form cyclic imines in a tandem addition-cyclization reaction. Imines themselves are activated by l-(trimethylsilyl)benzotriazole in the Grignard -eaction." Chiral Al-(alkylthio)imines give optically active homoallylic amine derivatives on reaction with allylmagnesium bromide. ... 

A collection of results obtained with the most effective catalyst systems is summarized in Figure 6.4. Noteworthy examples include the oxidation of a-aminoalcohols with no loss in enantiopurity and the oxidation of cis-allyhc alcohols without Z E isomerization. Stahl also demonstrated the chemoselective oxidation of primary diols to form lactones [22]. While ABNO provides efficient oxidation of symmetric diols, TEMPO discriminates between subtle steric differences in nonsymmetrical substituted diols. Cu/nitroxyl catalysts have also been applied to a variety of tandem reactions [23], perhaps the most noteworthy of which is the conversion of primary alcohols to nitriles via in situ condensation of ammonia with the aldehyde and subsequent dehydrogenation of the primary imine to the nitrile (Figure 6.5) [24]. 

The synthesis of chromenes, chromanes, coumarins, and related heterocycles via tandem reactions of salicylic aldehydes or salicylic imines with a,p-unsaturated compounds 07OBC1499. 

A tandem reaction of employing imination of o-halobenzaldehydes with fefi-butyl amine and subsequent palladacycle-catalyzed iminoannulation of internal alkynes has recently been developed by Wu and coworkers for the synthesis of isoquinolines (Scheme 11 2011T2969). 

Intermolecular and intramolecular HAMs are known. The transformation can be considered as a tandem reaction [2,3] consisting of three consecutive steps (i) hydroformylation, (ii) formation of an imine or an enamine, and (iii) reduction. Finally, the Af-alkylated amine is produced [4]. Clearly, these reactions can also be carried out in separate steps, but the application of uniform reaction conditions offers considerable advantages, such as the use of a single catalyst for the hydroformylation and the hydrogenation steps. Moreover, the equihbrium of the formation of the intermediate imine or enamine can be advantageously shifted by the irreversible hydrogenation in the last step [5]. 

The stability of allylboronates and the high level of diastereoselectivity in their additions to carbonyl compounds and imines represent very attractive attributes in organic synthesis. The examples in this chapter clearly show that recent advances in the preparation of allylboronates will help in furthering their applications. The development of efficient catalytic enantioselective allylboration methods and the invention of more powerful and more elaborate tandem reaction processes constitute two emerging areas for further development. 

Sun et al. reported a diversity-oriented parallel synthesis for benzimidazole 54 and pyrrolo-/pyrido-benzimidazo-lones 55 56 linked isoindolo-benzimidazolones on IL support xmder microwave irradiation by utilizing the cascade cyclization (Schemes 21 and 22). The research group used key tandem reactions (1) aminoalkylation of immobilized o-phenylenediamine with ketoacids, (2) intramolecular cyclization through secondary amine on electrophilic imine carbon toward pentacyclic aza-ring, and (3) second amidocyclization to deliver cycloamide ring [125]. 

Burrows and Keenan investigated tandem reactions on IRMOF-3, seeking to improve the scope of the reaction of an amine with an aldehyde by reducing the imine formed to give a product that is stable to hydrolysis. They showed that the imines generated on reaction with alkyl aldehydes were reduced to secondary amines on treatment with sodium cyanoborohydride (equation 3). ... 

In 2010, Monge et al. reported a one-pot tandem reaction by combining bifunctional thiourea and Au complex [77], affording dihydropynole derivatives in moderate yields and high enantioselectivities. The reaction was based on a bifunctional thiourea-catalyzed Mannich-type reaction and a subsequent Au-catalyzed alkyne hydroamination and isomerization of propargylated malononitrile and N-Boc-protected imines (Scheme 9.72). Notably, acidic additive proved cracial to prevent deactivation of the gold catalyst and enhance the reactivity and selectivity. 

Very recently. Barber et al. reported a tandem reaction combining bifunctional urea and Au(I) salt for the asymmetric synthesis of valuable tetrahydropyridine derivatives [80]. This reaction consisted of a urea-promoted nitro-Mannich reaction of an alkyne-tethered secondary nitroalkane to N-Boc-protected imines and an Au(I) complex-catalyzed intramolecular hydroamination and isomerization (Scheme 9.75). Notably, since the inherent Lewis basic tertiary amine-tethered urea would deactivate the Au catalyst, the reaction system was acidified by additional DPP before addition of an Au catalyst to ensure the success of the overall process. 

It has also been shown that dimethylsilyl enolates can be activated by diisopropylamine and water and exhibit a high reactivity toward iV-tosyl imines to give Mannich-type reaction products in the absence of a Fewis acid or a Bronsted acid.51 For example, the reaction of [(1-cyclohexen-l-yl)oxy]dimethylsilane with 4-methyl-A -(phenylmethylene)benzene sulfonamide gave re/-4-methyl-N- (f )-[(15)-(2-oxocyclohexyl)phenyl-methyl] benzenesulfonamide (anti-isomer) in 91% yield stereoselectively (99 1 anti syn) (Eq. 11.30). On the other hand, Fi and co-workers reported a ruthenium-catalyzed tandem olefin migration/aldol and Mannich-type reactions by reacting allyl alcohol and imine in protic solvents.52... 

Clerici and Porta reported that phenyl, acetyl and methyl radicals add to the Ca atom of the iminium ion, PhN+Me=CHMe, formed in situ by the titanium-catalyzed condensation of /V-methylanilinc with acetaldehyde to give PhNMeCHMePh, PhNMeCHMeAc, and PhNMeCHMe2 in 80% overall yield.83 Recently, Miyabe and co-workers studied the addition of various alkyl radicals to imine derivatives. Alkyl radicals generated from alkyl iodide and triethylborane were added to imine derivatives such as oxime ethers, hydrazones, and nitrones in an aqueous medium.84 The reaction also proceeds on solid support.85 A-sulfonylimines are also effective under such reaction conditions.86 Indium is also effective as the mediator (Eq. 11.49).87 A tandem radical addition-cyclization reaction of oxime ether and hydrazone was also developed (Eq. 11.50).88 Li and co-workers reported the synthesis of a-amino acid derivatives and amines via the addition of simple alkyl halides to imines and enamides mediated by zinc in water (Eq. 11.51).89 The zinc-mediated radical reaction of the hydrazone bearing a chiral camphorsultam provided the corresponding alkylated products with good diastereoselectivities that can be converted into enantiomerically pure a-amino acids (Eq. 11.52).90... 

The direct, stereoselective conversion of alkynes to A-sulfonylazetidin-2-imines 16 by the initial reaction of copper(l) acetylides with sulfonyl azides, followed, in situ, by the formal [2+2] cycloaddition of a postulated A-sulfonylketenimine intermediate with a range of imines has been described <06AG(E)3157>. The synthesis of A-alkylated 2-substituted azetidin-3-ones 17 based on a tandem nucleophilic substitution followed by intramolecular Michael reaction of primary amines with alkyl 5-bromo-4-oxopent-2-enoates has been... 

Recently, ruthenium-catalyzed tandem olefin migration/aldol-type or Mannich-type reactions have been developed with aldehydes or imines and allylic alcohols (Scheme 74). 

Ma et al. described the palladium(0)-eatalyzed three-component tandem double-addition-cyclization reaction of 2-(2,3-allenyl)malonate 218, Phi, and A-Ts-imine 219 for the stereoselective synthesis of 2,5-m-pyrrolidine 220... 

A related amination/rearrangement/cyclization tandem sequence had been introduced by Cossy [49]. Starting from cyclic epoxyketones 224 the reaction with propargylamines 225 caused an oxirane-opening condensation process to generate the enaminoketones 226. Upon heating in toluene to reflux, aza-Claisen rearrangement delivered the intermediate allenyl imines 227, which... 

Uneyama has described some interesting reactions of the N-aryl imines of ethyl trifluoropyruvate. Tandem alkylation/defluorination occurred (Eq. 97) upon exposure to diethylzinc, via attack at nitrogen and SN2 displacement of fluoride anion [279]. Interestingly, an alkylzinc halide reagent attacked regioselec-tively at carbon, perhaps the more expected outcome. 

Very recently examples of tandem Michael-azomethine ylide cyclization reactions have been presented.626 Thus, divinyl sulfone reacted with imine (124) in the presence of lithium bromide and tri-ethylamine to give (126) in 40% yield (Scheme 38). Presumably formation of Michael adduct (125), tau-tomerization to an azomethine ylide and ensuing intramolecular [3 + 2] cycloaddition afforded (126). Indeed, (125) could be independently synthesized and converted to (126) under the reaction conditions. The preference for initial Michael addition, rather than cycloaddition, was variable. When (124) and divinyl sulfone were treated with silver acetate and triethylamine in DMSO, intermolecular azomethine cycloaddition occurred giving (127) in 27% yield. 

The tandem cyclopropyl ring-opening/nitrilium ring-closing reaction in the presence of triflic acid results in the stereoselective formation of cyclic imines 161 (Scheme 5.67).699... 

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