Pyrrolo isoxazolidines

To overcome this problem, the group created an intramolecular variant in the form of an oxime ether-tethered cyclopropane, which underwent ring-opening in the presence of Yb(OTf>3 to afford a wide range of 2,5-trans-pyrrolo-isoxazolidines via an oxy-iminium intermediate (Scheme 10.46 and Table 10.15). 

It was thought this could be achieved by treatment of the alkoxylamine with Yb(OTf)3 first to generate the isoxazoli-dine 30 before addition of the aldehyde (Scheme 10.48). This would most likely result in the Z-oxy-iminium species as the most favored conformation to afford the cw-adduct [43]. The hypothesis was tested and resulted in the successful synthesis of 2,5-cw-pyrrolo-isoxazolidines with excellent yields and diastereoselectivity. An example is shown in Scheme 10.48. 

The group has also demonstrated the abdity of pyrrolo-isoxazolidines to be converted into highly substituted pyrrolidines via N-0 bond cleavage. This was achieved through hydrogenation in methanolic HCl to suppress the isomerization, which was observed under standard conditions to afford... 

Enantiomerically pure nitrones generated from aldehydes 73 underwent diastereoselective intramolecular 1,3-DC to afford pyrrolo[3,4-c]isoxazolidines 74 <00S365>. 

Spirocyclopropane isoxazolidines 75, obtained from alkylidenecyclopropane nitrones, underwent thermally induced selective rearrangement to pyrrolo[3,4-A]pyridinones 76 <00TA897>. The same adducts 75 in the presence of a protic acid afforded exclusively p-lactams 77 (57-60% yield) accompanied by ethylene extrusion <00JA8075>. 

Another example is provided by the quaternization of a saturated pyrrolo[l,2-6]isoxazole with methanesulfonyl chloride and further treatment with Zn powder in aqueous acetic acid <82T2627>. When compound (152) was treated with Zn in aqueous acetic acid at 50-60 °C, the isoxazolidine underwent reductive N—O bond cleavage with in situ cyclization to afford pyrrolizidine (153) in 86% yield. When (152) is treated directly with Zn in 90% aqueous acetic acid at higher temperature (130-140°C) and prolonged reaction time, pyrrolizidine (154) is obtained (Scheme 28) <85CPB351>. 

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