Nitrones 2- azetidinones

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). 

Alcaide and coworkers have reported in 2002 the synthesis of various types of racemic and homochiral 1,3,4-trisubstituted- or fused polycyclic (3-lactams (III and IV, respectively, Fig. 9) via intermolecular 1,3-dipolar cycloaddition reaction of 2-azetidinone-tethered nitrones with a variety of alkenes or alkynes [264]. 

They have also reported a direct route to optically pure, fused, or bridged tricyclic (3-lactams (III and IV, Fig. 18) as further advances in the intramolecular nitrone-alkene cycloaddition reactions of monocyclic 2-azetidinone-tethered alkenyl-aldehydes [289]. 

The intramolecular nitrone-alkene cycloaddition reaction of monocyclic 2-azetidinone-tethered alkenyl(alkynyl) aldehydes 211, 214, and 216 with Ar-aIkylhydroxylamincs has been developed as an efficient route to prepare carbacepham derivatives 212, 215, and 217, respectively (Scheme 40). Bridged cycloadducts 212 were further transformed into l-amino-3-hydroxy carbacephams 213 by treatment with Zn in aqueous acetic acid at 75 °C. The aziridine carbaldehyde 217 may arise from thermal sigmatropic rearrangement. However, formation of compound 215 should be explained as the result of a formal reverse-Cope elimination reaction of the intermediate ct-hydroxy-hydroxylamine C1999TL5391, 2000TL1647, 2005EJ01680>. 

The intramolecular 1,3-dipolar cycloaddition reactions of racemic as well as enantiopure 2-azetidinone-tethered nitrones with substituted alkenes and alkynes yielded isoxazolinyl-, or isoxazolidinyl-P-lactams 20, exhibiting good regio- and facial stereoselectivity <02JOC7004>. 

The formation of bicyclic nitrones of the 2-azetidinone A-oxide type, 32 and (33), has been achieved in a two-step route, through condensation of the corresponding 2-azetidinone tethered-alkenyl(alkynyl)aldehyde with hydroxylamine followed by phenylselenyl bromide treatment <02JOC7004>. 

Intramolecular 1,3-DC of 2-azetidinone-tethered alkenyl nitrones afforded novel tricyclic P-lactams, such as 101 and 102, amenable for further elaboration <05EJ01680>. 

An intramolecular variant of this catalytic enantioselective process was recently reported. Nitrone 70 was converted to azetidinone 71 in the presence of the CuBr 72a complex in 74% yield and with 88% ee (03AG4082). Ligand 72b was also quite effective, providing 71 with 90% ee, although the yield was only 47%. 

Finally, two novel routes to azetidinones from nitrones have been reported. Diphenylketen was found to react with a variety of A -alkylnitrones (83)... 

Cuprous acetylides c/5 -2-Azetidinones from acetylene derivs. and nitrones... 

Treatment of dimethylketene with ethoxyacetylene and related compounds affords 3>ethoxycydobutenones. Hydrolysis with acid then leads to cyclobutane-1,3-diones, the solution structures of which have been studied by n.m.r. In contrast diphenylketene reacts with the silylynamine (138) to give the butenyne (139). The reaction between nitrones and copper acetylides in pyridine gives rise to cis- and /raw-azetidinones. Deuteriation and isomerization studies indicate that... 

Miscellaneous Reactions. Isobutene, as the carbenium ion source for Ritter reactions, produces Al-r-butyl amides (eq 34). Isobutene undergoes highly regioselective cycloaddition with isocyanate to form azetidinones and with nitrones to yield isox-azolidines (eqs 35 and 36). Allyl thioethers are formed by the electrophilic addition of Benzenesulfenyl Chloride to isobutene (eq 37). Alkenylphosphonous dichlorides and alkenylthionophosphonic dichlorides are also formed by addition of PCI5 and P2S5 (eqs 38 and 39). ... 

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