Amines nucleophilic trapping

An amino alcohol can be formed in situ by the reaction of an iV-formylpiperizine 79 with epoxide 78 which then can be induced to cyclize to give the spiroaziridinium salt 80 (Equation 17) <2004TL4175>. The spiroaziridinium was not isolated but instead trapped by reaction with an amine nucleophile (cf. Section 12.20.6.1). 

The proposed catalytic cycle of the ruthenium-catalyzed intermolecular Alder-ene reaction is shown in Scheme 21 (cycle A) and proceeds via ruthenacyclopentane 100. Support for this mechanism is derived from the observation that the intermediate can be trapped intramolecularly by an alcohol or amine nucleophile to form the corresponding five-or six-membered heterocycle (Scheme 21, cycle B and Equation (66)).74,75 Four- and seven-membered rings cannot be formed via this methodology, presumably because the competing /3-hydride elimination is faster than interception of the transition state for these substrates, 101 and 102, only the formal Alder-ene product is observed (Equations (67) and (68)). 

Various peptide Michael acceptors have been described as a new class of inactivators for cysteine proteases. 5-7 The carbonyl group of the scissile peptide bond in the substrate is replaced by a nucleophile trapping moiety such as a vinylogous structure. An amino acid vinyl sulfone, l-(methylsulfonyl)-4-phenylbut-l-en-3-amine [H2NCH(Bzl)CH=CHS02Me] and a dipeptide derivative, Gly-HNCH(Bzl)CH=CHS02Me have both been prepared as inhibitors of cysteine proteases, leucine aminopeptidase and dipeptidyl peptidase I, respectively.1 5 A series of peptide vinyl sulfones has been synthesized as potent inhibitors for different cysteine proteases. 1A8 ... 

The nucleophilic trapping of azirines with secondary amines is a well-documented approach to the study of the photochemistry of aryl azides. The major product of irradiation of phenyl azide (118) in the presence of di-n-butylamine is the 3i/-azepine (119). A flash photolytic study has shown that... 

Nitrenes for the most part being electron deficient are highly electrophilic intermediates and therefore react with nucleophiles of all types. Tertiary amines, phosphines, sulfides, and sulfoxides all react with nitrenes to give ylides, in a reaction that is the reverse of their formation. In practice, dimethyl sulfoxide (DMSO) is often the most convenient nucleophilic trap since it can be used as the reaction solvent, and gives relatively stable sulfoximides (Scheme 6.40). Azo compounds, which are formally nitrene dimers, are common by-products in many nitrene reactions. However, the dimerization of two highly reactive species in solution is extremely unlikely on statistical grounds, and therefore the mechanism of azo compound formation probably involves the reaction of a nitrene, as an electrophile, with its precursor. 

A new split-Ugi reaction is the subject of a short review (37 references). The classical four-component reaction of aldehyde, primary amine, carboxylic acid and isocyanide has been modified using a secondary amine instead. This allows the Mumm-like rearrangement step to be avoided, freezing the reaction at the imino-anhydride intermediate, which is susceptible to alternative nucleophilic trapping. 

Zwitterionic borane adducts were reacted with trityl cation salts to provide a series of primary borenium cation derivatives (Scheme 12). For example, the A-heterocyclic carbene (NHC) borane (45) was prepared from the corresponding NHC (44). With the addition of the trityl salt, the dicationic dimer (46) was isolated. Product (46) was characterized by X-ray crystallography and trapped by nucleophiles. Its observation by NMR resonance (5 + 10.6) is in accordance with the GIAO calculated value (5 + 0.8). Similar borenium dications were generated from amine nucleophiles, such as compound (47). The authors considered the question why some borenium ion salts... 

Encouraged by these findings, we extended our study to develop aminotrifluor-omethylation of alkenes. Acetonitrile (MeCN) is an (V-nucleophile known as an aminative carbocation trapping agent (Ritter-type reaction). We found the... 

Other Reactions. Treatment of an active hydroxy compound with 2,2 -dipyridyl disulfide and n-BuyP yields the corresponding thiopyridyl derivative. This methodology has been applied to the preparation of 5-arylthio-5 -deoxyribonucleosides (eq 8). Monophosphate esters [R0P(0)(0H)2] will react similarly to form the activated triphenylphosphonium adduct, which, in the absence of an added external nucleophile, dimerizes yielding a pyrophosphate. A-Methylimidazole has been found to catalyze this transformation. The addition of alcohols or amines, however, traps the phosphoryloxyphosphonium salt as the mixed diphosphate ester or mixed ester/amide, respectively (eq 9). Chlorotrimethylsilane and (pyS)2 have also been reported to facilitate the oxidation of phosphites to phosphates. ... 

This synthetic method can also be applied to other nucleophiles like amines (Sect. 5.2.4) or alcohols [65] (Scheme 5.6). With poorer nucleophiles such as 2,2 -dimethylaziridine, the nucleophilic trapping of the carbocationic intermediate is not fast enough to prevent decomposition. However, using EtOH instead of CH2CI2 as solvent provides sufficient stabilization to the carbocation to afford the thiophosphine-aziridine 10 in good yields [66], even though contaminated by the... 

In addition to alcohols, some other nucleophiles such as amines and carbon nucleophiles can be used to trap the acylpalladium intermediates. The o-viny-lidene-/j-lactam 30 is prepared by the carbonylation of the 4-benzylamino-2-alkynyl methyl carbonate derivative 29[16]. The reaction proceeds using TMPP, a cyclic phosphite, as a ligand. When the amino group is protected as the p-toluenesulfonamide, the reaction proceeds in the presence of potassium carbonate, and the f>-alkynyl-/J-lactam 31 is obtained by the isomerization of the allenyl (vinylidene) group to the less strained alkyne. 

In the presence of cyclohexyl amine the photolysis of the dienone (58) gives the cyclohexyl amide expected from dienone ring fission and reaction of cyclohexyl amine with the ketene. However, in the presence of weaker nucleophiles the ring opened product is not trapped and instead there is a relatively slow formation of phenols<36,44) ... 

In solution, l-(ot-aminoalkyl)benzotriazoles 562 are in equilibrium with iminium cation 563 and hence with their benzotriazole-2-yl isomers 564 (Scheme 89). Protonation or complexation of the benzotriazolyl moiety (e.g., Mg, Zn, B, A1 reagents) facilitates the transformation. Intermediate iminium cations 563 can be trapped by nucleophiles providing synthetic pathways to various amines. Many such reactions are described in CHEC-II(1996) <1996CHEC-11(4)1 >, and some newer results are compiled in reviews <2005T2555>. 

There have, from time to time, been suggestions that electron transfer may mediate in processes which are formally ionic substitution reactions. Whilst such mechanisms have been established for a small number of systems (Kornblum, 1975 Bunnett, 1978), in other instances the evidence is less substantial. For example, dialkylaminyl spin adducts may be observed when secondary amines are allowed to react with picryl chloride in the presence of MNP (Bil kis and Shein, 1974). This can be interpreted in terms of Scheme 12, but alternatives involving nucleophilic addition to the trap merit consideration. 

The methodology did not work for secondary amines, thus suggesting the formation of an isocyanate as intermediate (Scheme 27, MX2 = Pdl2, [OX] = (1/2) O2]. However, by reacting a primary amine in the presence of a secondary nucleophilic amine, a general and selective synthesis of trisubstituted ureas has been achieved, through trapping of the isocyanate intermediate by the secondary amine (Eq. 52) [274,275]. 

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