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. 2009 Jul 1;82(7):1353-1364.
doi: 10.1351/PAC-CON-09-12-09.

Phosphoramidite-Rhodium Complexes as Catalysts for the Asymmetric [2+2+2] Cycloaddition of Alkenyl Isocyanates and Alkynes

Rebecca Keller Friedman  1 , Kevin M Oberg, Derek M Dalton, Tomislav Rovis
Affiliations

Phosphoramidite-Rhodium Complexes as Catalysts for the Asymmetric [2+2+2] Cycloaddition of Alkenyl Isocyanates and Alkynes

Rebecca Keller Friedman et al. Pure Appl Chem. .

Abstract

The discovery and development of the asymmetric rhodium-catalyzed [2+2+2] cycloaddition of alkenyl isocyanates and exogenous alkynes to form indolizinone and quinolizinone scaffolds is described. This methodology has been expanded to include substituted alkenes and dienes, a variety of sterically and electronically diverse alkynes, and carbodiimides in place of the isocyanate. Through X-ray analysis of Rh(cod)/phosphoramidite complexes, additives that modify the enantio-determining step, and other experimental data, a mechanism has been proposed that explains lactam, vinylogous amide, and pyridone products and the factors governing their formation. Finally, we have applied this methodology to the synthesis of (+)-lasubine-II and (-)-209D.

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Figures

Fig. 1
Fig. 1
Indolizidine and quinolizidine natural products
Fig. 2
Fig. 2
Proposed mechanistic pathway
Fig. 3
Fig. 3
X-ray crystal structures of Rh(cod)Cl/phosphoramidite
Fig. 4
Fig. 4
Explanation of product selectivity
Scheme 1
Scheme 1
Initial reaction scope
Scheme 2
Scheme 2
Phosphoramidite ligand screen
Scheme 3
Scheme 3
Select examples of terminal alkynes
Scheme 4
Scheme 4
Product selectivity shift
Scheme 5
Scheme 5
Scope with L7
Scheme 6
Scheme 6
Synthesis of (+)-lasubine II and (−)-209D.
Scheme 7
Scheme 7
Scope of 1,1-disubstituted alkenes
Scheme 8
Scheme 8
Unsymmetrical alkyne incorporation
Scheme 9
Scheme 9
Carbodiimide scope
Scheme 10
Scheme 10
Methyl nicotinate additive effect
Scheme 11
Scheme 11
[4+2+2] cycloaddition and proposed mechanism
See this image and copyright information in PMC

References

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