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In recent years, the use of Rh(II) as a catalyst for the generation of carbonyl ylides as 1,3-dipoles has proven to be valuable in natural product synthesis.
To demonstrate the versatility of this methodology, various [3+2] cycloadditions were attempted to trap the resulting dipole to generate an array of cycloadducts.
Previously in the Padwa lab, diazo compounds 1 have been shown to undergo Rh(II) catalyzed cyclizations to generate 1,3-dipoles 2 (Scheme I).
These dipoles were then reacted with various alkenes inter- and intramolecularly to yield cycloadducts such as 3 in high yield and selectivity.
Scheme 1
To test out bimolecular cycloadditions of an isatin derivative two similar systems were prepared for comparison of yields and selectivity. Scheme II and III describe
the synthesis of these diazo isatin derivatives.
Scheme 2
Scheme 3
Bimolecular Cycloadditions with OMe Protecting Group
Scheme 4
Bimolecular Cycloadditions with OTBS Protecting Group
Scheme 5
The 3:1 mixture methyl propiolate for example found in the OTBS derivative compared to the 1:1 mixture found in the OMe derivative showed that
sterics (not just electronics) play a large role in the selectivity of the Rh(II) cycloaddition.
Intramolecular Cycloadditions with an All Carbon Side Chain
Scheme 6
Scheme 7
Intramolecular Cycloadditions with an Oxygen-Containing Side Chain
Scheme 8
Scheme 9
Scheme 10
Intramolecular Cycloadditions Comparing Carbon and Oxygen Side Chains
Scheme 11
Scheme 12
Scheme 13
The 5:1 ratio observed in scheme XI, exclusive product in scheme XII, and 10:1 ratio in scheme XIII indicate that oxygen containing side chains control
the cycloadditions. Experiments are in progress to learn more about the reasons for this observation.
This material is based upon work supported by the Howard Hughes Medical Institute under Grant No.52005873, by the National Science Foundation (NSF),
and by Student Inquiry Research Experience award from the Office of Undergraduate Studies, Emory College.
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