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. 2015;6(9):5105-5113.
doi: 10.1039/c5sc01710f.

Configurationally Stable, Enantioenriched Organometallic Nucleophiles in Stereospecific Pd-Catalyzed Cross-Coupling Reactions: An Alternative Approach to Asymmetric Synthesis

Chao-Yuan Wang  1 , Joseph Derosaa  2 , Mark R Biscoe  1
Affiliations

Configurationally Stable, Enantioenriched Organometallic Nucleophiles in Stereospecific Pd-Catalyzed Cross-Coupling Reactions: An Alternative Approach to Asymmetric Synthesis

Chao-Yuan Wang et al. Chem Sci. 2015.

Abstract

Several research groups have recently developed methods to employ configurationally stable, enantioenriched organometallic nucleophiles in stereospecific Pd-catalyzed cross-coupling reactions. By establishing the absolute configuration of a chiral alkyltin or alkylboron nucleophile prior to its use in cross-coupling reactions, new stereogenic centers may be rapidly and reliably generated with preservation of the known initial stereochemistry. While this area of research is still in its infancy, such stereospecific cross-coupling reactions may emerge as simple, general methods to access diverse, optically active products from common enantioenriched organometallic building blocks. This minireview highlights recent progress towards the development of general, stereospecific Pd-catalyzed cross-coupling reactions using configurationally stable organometallic nucleophiles.

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Figures

Fig. 1
Fig. 1. Catalytic cycle and competing processes for Pd-catalyzed cross-coupling reactions of secondary nucleophiles and aryl electrophiles.
Fig. 2
Fig. 2. Inverse relationship between configurational stability and nucleophilicity for main group organometallic nucleophiles.
Fig. 3
Fig. 3. Potential mechanisms for the stereospecific transmetallation of optically active alkyltin and alkylboron nucleophiles to palladium.
Fig. 4
Fig. 4. Stereospecific Pd-catalyzed cross-coupling reaction of an activated, enantioenriched alkylstannane and benzoyl chloride as reported by Falck.
Fig. 5
Fig. 5. Stereospecific Pd-catalyzed cross-coupling reactions of activated, enantioenriched benzylstannanes and benzoyl chloride as reported by Chong.
Fig. 6
Fig. 6. Stereospecific Pd-catalyzed cross-coupling reactions of activated, enantioenriched allylic stannanes and aryl electrophiles as reported by Hoppe.
Fig. 7
Fig. 7. Stereospecific Pd-catalyzed cross-coupling reactions of activated, enantioenriched alkylstannanes and aryl/alkenyl iodides as reported by Falck.
Fig. 8
Fig. 8. Stereospecific Pd-catalyzed cross-coupling reactions of unactivated, enantioenriched secondary alkylcarbastannatranes and aryl bromides as reported by Biscoe.
Fig. 9
Fig. 9. Stereospecific Pd-catalyzed cross-coupling reaction of an enantioenriched benzylstannane and an aryl bromide as reported by Liao.
Fig. 10
Fig. 10. Stereospecific cross-coupling reactions of enantioenriched benzylboronic esters and alkyl iodides as reported by Crudden.
Fig. 11
Fig. 11. Stereospecific Pd-catalyzed cross-coupling reactions of enantioenriched dibenzylic organoboronic esters and aryl iodides as reported by Crudden.
Fig. 12
Fig. 12. Stereospecific Pd-catalyzed cross-coupling reactions of enantioenriched alkyl β-trifluoroboratoamides and aryl chlorides as reported by Molander.
Fig. 13
Fig. 13. Stereospecific Pd-catalyzed cross-coupling reactions of enantioenriched α-(acylamino)benzylboronic esters and aryl electrophiles as reported by Suginome and Ohmura.
Fig. 14
Fig. 14. The effect of additives on the stereospecificity of Pd-catalyzed cross-coupling reactions of enantioenriched alkyl β-trifluoroboratoamides and aryl bromides as reported by Suginome and Ohmura.
Fig. 15
Fig. 15. Stereospecific Pd-catalyzed cross-coupling reactions of enantioenriched 1-(benzyloxy)alkyltrifluoroborates and aryl chlorides as reported by Molander.
Fig. 16
Fig. 16. Stereospecific Pd-catalyzed cross-coupling reactions of enantioenriched 3,3-diboronyl carboxyesters and aryl/vinyl bromides as reported by Hall.
Fig. 17
Fig. 17. Stereoinvertive transmetallation in the Pd-catalyzed cross coupling of a geminal diboronyl reagent and an aryl iodide as reported by Morken.
Fig. 18
Fig. 18. Stereospecific Pd-catalyzed cross-coupling reactions of unactivated, secondary alkyl trifluoroborates and aryl chlorides as reported by Biscoe.
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