Synfacts 2021; 17(01): 0039
DOI: 10.1055/s-0040-1719528
Metals in Synthesis

Enantioselective Pd-Catalyzed Trimethylenemethane Cycloadditions of All-Carbon 1,4-Dipoles

Contributor(s):
Mark Lautens
,
Rachel Ross
Trost BM, *, Jiao Z, Liu Y, Min C, Hung C.-IJ. Stanford University, USA
Palladium-Catalyzed Enantioselective Cycloadditions of Aliphatic 1,4-Dipoles: Access to Chiral Cyclohexanes and Spiro[2.4]heptanes.

J. Am. Chem. Soc. 2020;
142: 18628-18636
DOI: 10.1021/jacs.0c08348.
 

Significance

Trost and co-workers report the asymmetric syntheses of all-carbon chiral cyclohexanes and spiro[2.4]heptanes using palladium-catalyzed cycloadditions of aliphatic 1,4-dipoles. Using various phosphoramidite and diamidophosphite ligands, several biologically relevant scaffolds were generated in good regio-, diastereo- and enantio­selectivity. The synthetic utility was demonstrated through gram-scale syntheses of each scaffold, and derivatizations included the ozonolysis and hydrolysis reactions shown.


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Comment

Upon scale up, the palladium and ligand loading could be decreased to 2 and 4 mol%, respectively, and the cyclohexane products were formed with higher regioselectivity than the spirocycles. Interestingly, a resonance effect between the pyridine nitrogen and palladium cation center was found to be necessary for the examples with heterocyclic arenes as the second electron-withdrawing group.


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Publication History

Publication Date:
16 December 2020 (online)

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