Tethered amination reactions

This tethered ferrocenyl-based Pd complex on MCM-41 (17) was then used for the catalytic amination reaction between cinnamyl acetate and benzylamine (40 °C, THF) [59]. In this case, confinement of the catalyst results in profound changes in regio- and enantioselectivity. When the homogeneous equivalent is used to catalyze the reaction, the straight chained derivative is the sole product. Similar results (only 2% of the branched product) were obtained when the catalyst was tethered to the surface of the non-porous silica Cabosil. When tethered inside the pores of MCM-41 a major change occurred in that now the branched product accounts for about 50% and a change in e.e. from 49% e.e. when anchored to the Cabosil support to +99% when anchored inside the MCM-41 pore could be observed. If the catalyst s chirality was reversed in the MCM-41 immobihzed case, so was the chirality of the product (measured at 93% e.e.) [60]. 

The only way to realize an enantioselective Biginelli reaction is to conduct it intramolecularly where the enantiopure urea and aldehyde portions are tethered. This reaction was the key step in L.E. Overman s total synthesis of guanidine alkaloid 13,14,15-lsocrambescidin 800. An optically active guanidine aminal was reacted with an enantiopure (3-keto ester in trifluoroethanol to afford 1-iminohexahydropyrrolo[1,2-c]pyrimidine carboxylic ester with a 7 1 trans selectivity between CIO and Cl3 positions. 

Silyl tethered amines are used frequently in amide-forming coupling reactions [e.g.. Fig. 16(c)] (169, 170). Isocyanate compounds are also commercially available, and have been used in the immobilization of enzymes within the sol-gel pores (171). These isocyanates can also be used to prepare silylated phen ligands that have been used in our own studies (172). Silylated isocyanates have... 

A few examples of Pd"-catalyzed carboamination reactions between alkyne-tethered amines and aryl halides have also been reported [28d, 47]. For example, treatment of amino ester derivative 50 with Phi in the presence of K2CO3 using Pd(PPh3)4 as catalyst led to the formation of 51 in 80% yield with complete retention of enantiomeric purity (Eq. (1.23)) [28d]. In contrast to the Pd"-catalyzed carboamination... 

Palladium-catalyzed carbonyiative reactions of aryl or alkenyl bromides bearing pendant nitrogen nucleophiles have been studied for over 30 years, and have proven useful for the construction of a variety of different heterocyclic compounds [96]. For example, treatment of 140 with catalytic amounts of Pd(OAc)2 and PPha in the presence of BU3N under an atmosphere of CO afforded lactam 141 in 65% yield (Eq. (1.56)) [96a]. This transformation presumably occurs via oxidative addition of the aryl bromide to Pd to provide 142, which undergoes insertion of CO into the Pd—C bond to yield 143. Intramolecular capture of the acylpaUadium intermediate 143 by the tethered amine gives the desired heterocyclic product... 

A strategy directed at exploiting another bimetallic framework with tethered carboxylate groups led to the isolation of an unusual dirhodium(ll) tetracarboxylate catalyst with calbc[4]arene (CLX), which was synthesized (Scheme 9.17) and used in C-H amination reactions [143] the structures of... 

Other similar palladium-catalyzed and intramolecular allylic oxidation reactions using tethered O- and A(-nucleophiles in conjunction with molecular oxygen (as a reoxidant) have been described. These provide a range of ring-fused heterocycles in good to excellent yield (eq 76). Related intermolecular amination reactions have also been described. ... 

For encapsulated catalysts, amination reaction was carried out in a high pressure autoclave containing aniline, iodobenzene, catalyst, and potassium ferf-butoxide (KOt-Bu) at 408 K for 14 h. For tethered catalysts, the amination reaction was carried out in a two necked flask under reflux at 385 K for 10-12 h. 

The aza-[2,3]-Wittig rearrangement of a vinylaziridine-derived quaternary azir-idinium ylide (i.e., [2,3]-Stevens rearrangement) has recently been reported (Scheme 2.53) [86], The aziridinium ylide 219, generated by the intramolecular reaction of a copper carbenoid tethered to a vinylaziridine, underwent a [2,3]-Ste-vens rearrangement to furnish the bicydic amine 220 with the indolizidine skeleton. 

The second option involves the incorporation of either chiral amines or chiral alcohols into the heteroatom-carbene side chain (R ), which represents the most versatile approach to diastereoselective benzannulation. The optically pure (2R,3R)-butane-2,3-diol was used to tether the biscarbene complex 37. The double intramolecular benzannulation reaction with diphenylbutadiyne allowed introduction of an additional stereogenic element in terms of an axis... 

Regarding bis-NHC chelating ligands, several structures that differ in the motifs used for the enlargement of the tether have been proposed as catalysts for the Mizoroki-Heck reaction. They range from non-functionalised aliphatic chains [23-25] to phenyl [26], biphenyl [27], binaphthyls [28] and to chains containing additional coordination positions like ethers [29], amines [30], and pyridines in an evolution towards pincer complexes [31-35], In most cases, the activity of aryl bromides in Mizoroki-Heck transformations was demonstrated to be from moderate to high, while the activation of chlorides was non-existent or poor (Scheme 6.7). 

For conversion of amide to other acid derivatives, a novel synthesis of urea glycosides in aqueous media has been reported via the reaction of Steyermark s glucosyl carbamate with amines in good yields (Eq. 9.17).38 This method was successfully applied to develop a new route to the synthesis of urea-tethered neo-glycoconjugates and pseudooligosaccharides. 

Other radical cyclization approaches to the synthesis of piperidines include a CAN-mediated stereoselective cyclization of epoxypropyl cinnamyl amines <06TL705> and a cyclization of (-trimethylsilylmethylamine radical cation, generated via a photoinduced electron transfer reaction to a tethered -functionality <06JOC8481>. 

Amines and amides undergo oxidation at or adjacent to nitrogen (Scheme 27). A neutral amine, for example, can be oxidized to afford a cation radical (117 to 116). Similarly, electrooxidation of the anion produced via deprotonation of a secondary amine leads to an aminyl radical (119) that is capable of participating in carbon-nitrogen bond-forming reactions with remotely tethered alkenes. 

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