Spiro cyclopropane-1,4-isoxazolidine

Spiro- and 4,5-bis(spiro)-cyclopropane isoxazolidines 85a and 85b prepared by 1,3-DC of acyclic nitrones with methylenecyclopropane (MCP), MCP derivatives or bicyclopropylidene (BCP) smoothly underwent fragmentation upon heating in the presence of a protic acid to yield monobactams 86a and spirocyclopropanated p-lactams 86b in moderate to good yields (56-96%) <04EJ02205 04EJO4158>. 

A new selective thermal cascade ring-enlargement process of 4-chloro-substituted spiro[cyclopropane-l,5 -isoxazolidines], leading to a new method for the synthesis of the indolizine skeleton, has been reported (see Scheme 17). Apparently, the process is made possible by the presence of a chlorine substituent on the carbon a to the spirocyclopropane ring which facilitates a cyclopropyl-to-cyclobutyl ring enlargement mediated by a polar solvent. 

The p-lactamic ring was also formed by the acidic thermal rearrangement of spiro[cyclopropane-l,5 -isoxazolidines], [209]. The rearrangement was almost instantaneous at 90°C, as the starting material was completely converted after 2 min. 

Treatment of bis-spirocyclopropanated isoxazolidines 551 with trifluoroacetic acid in acetonitrile furnishes 3-spiro-cyclopropanated azetidin-2-ones 552 in excellent yields (Equation 226) <2004EJ04158>. 

The Cu(II)-BOX-complex-catalysed 3 + 2-cycloaddition of nitrones with 2-alkenoyl pyridine A -oxide formed isoxazolidines with high diastereo-and enantio-selectivities. ° Microwave catalysis of the 1,3-dipolar cycloaddition of 0 nitrones with tetraethyl l,l-ethenediylbis(phosphonate) produced isoxazolidine (g) bisphosphonates in the absence of solvents. The intennolecular 1,3-dipolar cycloaddition of dimethyl 2-benzylidenecyclopropane-l,l-dicarboxylate with C-aryl or C-amido nitrones formed spiro(cyclopropane-l,4-isoxazolidine) cycloadducts The 1,3-dipolar cycloaddition of nitrones (52) with vinylidenecyclopropanes (53) produced 4-cyclopropylidine-isoxazolidines (54) in moderate yields (Scheme 16). ... 

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. ... 

Chmielewski and colleagues reported a Bu3SnH-mediated radical-induced isoxazoli-dine-isoxazolidin-5-one transformation (equation 99)778, while Sulsky and coworkers described conformational switching in the synthesis of a spiro[2H-indol]-3(lH)-ones (e.g. 122) by radical cyclization, an example of which is depicted in equation 100787. In this final example, Takekawa and Shishido described the selective cleavage of substituted cyclopropanes via stannane-induced radical fragmentation, an example of which is illustrated in equation 101791. 

Isoxazolidines with a highly strained cyclopropane ring spiro-fused at the 5-position show a special reactivity and can be converted into different classes of azaheterocycles depending on the substitution pattern and the reaction conditions <2004M649>. 

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