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. 2009 Nov;38(11):3149-59.
doi: 10.1039/b816702h. Epub 2009 Sep 15.

Multi-component cycloaddition approaches in the catalytic asymmetric synthesis of alkaloid targets

Stéphane Perreault  1 , Tomislav Rovis
Affiliations

Multi-component cycloaddition approaches in the catalytic asymmetric synthesis of alkaloid targets

Stéphane Perreault et al. Chem Soc Rev. 2009 Nov.

Abstract

Cycloaddition reactions are attractive strategies for the rapid formation of molecular complexity in organic synthesis, as multiple bonds are formed in a single process. To this end, several research groups have been actively involved in the development of catalytic methods to activate readily accessible pi-components to achieve cycloadditions. However, the use of C-N pi-components for the formation of heterocycles by these processes is less well developed. It has been previously demonstrated that the combination of different isocyanates with two alkynes yields pyridones of several types by metal-catalyzed [2 + 2 + 2] cycloadditions. The potential of this chemistry has been extended to alkenes as C-C pi-components, allowing the formation of sp(3)-stereocenters. In this tutorial review directed towards [n + 2 + 2] cycloadditions of heterocumulenes, alkynes and alkenes, the recent advances in the catalytic asymmetric synthesis of indolizidine, quinolizidine and azocine skeletons are discussed.

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Figures

Fig. 1
Fig. 1
Some indolizidine- and quinolizidine-based natural products
Scheme 1
Scheme 1
General scheme for metal-catalyzed generation of heterocycles
Scheme 2
Scheme 2
Intra- and intermolecular strategies for [2+2+2] cycloadditions with heterocumulenes
Scheme 3
Scheme 3
Rh-catalyzed [2+2+2] cycloaddition of alkenyl isocyanates and internal symmetrical alkynes
Fig. 2
Fig. 2
Phosphoramidite ligands used in the Rh-catalyzed [n+2+2] cycloadditions of heterocumulenes
Scheme 4
Scheme 4
Enantioselective Rh-catalyzed [2+2+2] cycloaddition of alkenyl isocyanates and aliphatic terminal alkynes
Scheme 5
Scheme 5
Total synthesis of (−)-209D
Scheme 6
Scheme 6
Enantioselective Rh-catalyzed [2+2+2] cycloaddition of alkenyl isocyanates and aromatic terminal alkynes
Scheme 7
Scheme 7
Total synthesis of (+)-lasubine II
Fig. 3
Fig. 3
Rhodium-ligand crystal structures
Scheme 8
Scheme 8
Current mechanistic understanding for the Rh-catalyzed [2+2+2] cycloadditions
Scheme 9
Scheme 9
Steric and electronic contributions to rationalize the partitioning between the lactam and vinylogous amide product
Scheme 10
Scheme 10
Proposed approach to the synthesis of bicyclic amidines
Scheme 11
Scheme 11
Enantioselective Rh-catalyzed [2+2+2] cycloaddition of alkenyl carbodiimides and terminal alkynes
Fig. 4
Fig. 4
Proposed Rh(III)-complexes for the enantioselective [2+2+2] cycloaddition of alkenyl isocyanates and tolanes
Scheme 12
Scheme 12
Enantioselective Rh-catalyzed [2+2+2] cycloaddition of alkenyl isocyanates and tolanes
Scheme 13
Scheme 13
Enantioselective Rh-catalyzed [2+2+2] cycloaddition of alkenyl isocyanates and unsymmetrical internal alkynes
Fig. 5
Fig. 5
Two manzamine alkaloids
Scheme 14
Scheme 14
Enantioselective Rh-catalyzed [4+2+2] cycloaddition of dienyl isocyanates and terminal alkynes
Scheme 15
Scheme 15
Proposed mechanism for the Rh-catalyzed [4+2+2] cycloaddition of dienyl isocyanates
See this image and copyright information in PMC

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