Alkynes reactions with nitrone

In the racemic version, the reaction of various terminal alkynes 105 with nitrones 106 was carried out using 10 mol % of Cul in pyridine-DMF at room temperature. As expected, the corresponding azetidinones 107 were formed as a mixture of trans and czs-isomers, along with the imines 108 (Scheme 30). 

The reaction of nitrones with terminal alkynes proceeds in excellent yields and high purity, in the presence of stoichiometric quantities of diethylzinc and zinc triflate (219, 661-663). To optimize the process of diastereoselective addition of terminal alkynes to chiral nitrones, ZnCl2 and NEt3 in toluene were used. This reaction protocol is facile to perform, cost-effective and environmental friendly (664). 

Nitrone cycloaddition reactions with alkynes have been widely used for the synthesis of imidazolidine nitroxides (736) and (737), containing chelating enam-ino ketone groups (821). Different heterocyclic systems were obtained, such as 3-(2-oxygenated alkyl)piperazin-2-ones (738) (822), also compounds containing the isoxazolo[3,2-i]indole ring system (739) (823) and a new class of ene-hydroxylamino ketones- (l )-2-( 1-hydroxy-4,4,5,5-tetraalkylimidazolidin-2-ylidene)ethanones (740) (824) (Fig. 2.46). 

Another interesting cascade involving nitrones is the copper catalyzed reaction with alkynes to produce p-lactams that was originally reported by Kinugasa (72CC466). Stoichiometric amounts of copper(I) phenylacetylide (61) react with various aryl nitrones 62 in pyridine to give p-lactams 63 in 50-60% yield (equation (2)). In each case, only the czs-lactams were isolated. 

Hetero-[2 + 2]-cycloaddition has been extensively investigated since this process provides a variety of /Mactones and /Mactams.178 There are two types of hetero-[2 + 2]-cycloaddition reaction, as illustrated in Scheme 114 one is the reaction of ketenes with aldehydes or imines to give lactones and lactams (Scheme 114, route a) and the other is the reaction of alkynes with nitrones to give lactams (Scheme 114, route b).179... 

The reaction of the triazole (323) with carbon disulphide does not yield the expected triazolopyrimidine (325) the triazolothiazine (324) is formed instead (Scheme 125). Derivatives of pyrrolo[3,2- f]pyrimidine (327) are obtained, in 54—64% yield, from pyrimidotriazines (326), the initial step being one of cycloaddition of the alkyne to the nitrone function (Scheme 126)/ ... 

The same patent and publication (07W0106818,15JFC121) mentioned the preparation of 4-SF5-2,3,5-trisubstituted-4-isoxazolines 171a—d in case when nitrones 170a—c were used as 1,3-dipoles in cycloaddition reactions with SFs-alkynes 129a,c,d (Scheme 53). 

When a nitrone reacts with a vinyl ether, an isoxazolidine is formed via a [3+21-cycloaddition reaction.58 Similar reaction with an alkyne gives an isoxazole.58... 

The copper-catalysed 3 + 2-cycloaddition reactions of nitrones with alkynes leading to / -lactams have been extensively reviewed. The 3+2-cycloaddition reactions of dialkyl-substituted 2-benzylidenecyclopropane-l,l-dicarboxylates (54) and C-carbamoyl nitrones (53) produced simple isomeric spiro[cyclopropane-l,4-isoxazolidine] cycloadducts (55), which are readily transformed into isoxazolidine-fused / -lactams (56) in high yields (Scheme 15). BINOL-derived chiral phosphorami-date Au(l) catalysts have been used to catalyse the 3+2-cycloaddition of A(-allenyl amides with nitrones to produce chiral 4-alkylidenyl isoxazolidines in high yields and excellent enantioselectivity (up to 99% cc). The 3+2-cycloaddition of a-phenylnitroethene and (Z)-CA -diphenylnitrone in polar media (nitromethane and water) yielded 3,4-fra 5 -2,3,5-triphenyl-4-nitroisoxazolidine via a zwitterionic, two-step mechanism. ... 

The asymmetric version of this reaction has been carried out using nitrone 46a and terminal alkynes 48 in the presence of HETPHOX 49 ligand as catalyst to afford the -lactams 50 in good diastereoselectivity but moderate enantioselectivity (Scheme 3.19) [52]. Diastereoselectivity of the products depends on the nature of the alkynes. Most alkynes afforded the ds-adducts, whereas trans-products were obtained with the 3,5-trifluoromethylacetylene. Very recently, Chen and coworkers [53] reported a novel efficient catalyst, TOX [chiral tris(oxazoHne)] 51/Cu(I) complex, for the asymmetric Kinugasa reaction of terminal alkynes 48a with C-aryl nitrones 46 to afford the isomeric fi-lactams 52 and 53 in highly enantio- and diastereoselective manners (Scheme 3.20). The highly enantioselective Kinugasa reaction of nitrones 46 with terminal alkynes 48a in the presence of IndaBox 54/Cu(OTf)2 and dibutylamine has been reported to yield the isomeric P-lactams 52 and 53 (Scheme 3.21) [54]. 

Thus the simplest aliphatic monomeric nitrone (369) has been studied in its reactions with alkynes and isocyanates. Problems were encountered since the nitrone was found to be in the form of an adduct (370) with excess pivaldehyde, although it is possible to remove the aldehyde in vacuo at the melting point. The simple products of cycloaddition (371) and (372) were isolated in good yield. 

On the other hand, Suzuki and co-workers have demonstrated that copper(I) species can promote the reaction of vinyl halides with terminal alkynes without the need for a palladium catalyst however, as in the Castro reaction, a stoichiometric amount of copper salt is needed. By contrast, Miura and coworkers found that aryl and vinyl iodides smoothly react with terminal alkynes in the presence of a catalytic amount of copper iodide using potassium carbonate as base when an appropriate amount of triphenylphosphine is added. Pyridine or 1,2-bis(diphenylphosphino)ethane (dppe) have been used as ligands in the case of Cul-catalyzed reaction of terminal alkynes with nitrones. ... 

As an alternative, iridium complexes show exciting catalytic activities in various organic transformations for C-C bond formation. Iridium complexes have been known to be effective catalysts for hydrogenation [1—5] and hydrogen transfers [6-27], including in enantioselective synthesis [28-47]. The catalytic activity of iridium complexes also covers a wide range for dehydrogenation [48-54], metathesis [55], hydroamination [56-61], hydrosilylation [62], and hydroalkoxylation reactions [63] and has been employed in alkyne-alkyne and alkyne - alkene cyclizations and allylic substitution reactions [64-114]. In addition, Ir-catalyzed asymmetric 1,3-dipolar cycloaddition of a,P-unsaturated nitriles with nitrone was reported [115]. 

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