Controlling Competing Pathways in Palladium-Catalyzed Tandem/Domino Reactions of Hindered Grignard Reagents with 1,2-Dihaloarenes and 2-Haloaryl Tosylates

Abstract

Based on the hypothesis that individual elementary steps in the catalytic cycle of Pd-catalyzed cross-coupling reactions could be controlled, we explored the opportunity of controlling the transmetalation step to develop new reactions. The results of these studies, summarised in this Account, may lead to the development of other new tandem/domino reactions by using the same or similar concepts of controlling the transmetalation step and the palladium-associated aryne-generation strategy.

• 1 Introduction

• 2 Annulative Tandem Reactions Based on Palladium(0)/t-Bu₃P-Catalyzed Cross-Coupling/sp³ C-H Bond Activation: Efficient Synthesis of Substituted Fluorenes

• 3 Pd(OAc)₂-Catalyzed Annulative Domino Reactions of
  1-Chloro-2-haloarenes with Hindered Grignard Reagents via Palladium-Associated Arynes

• 4 Pd(OAc)₂-Catalyzed Annulative Domino Reactions of
  2-Haloaryl Tosylates with Hindered Grignard Reagents via Palladium-Associated Arynes

• 5 Summary

Key words

palladium - cross-coupling - C-H activation - tandem ­reactions - domino reactions

References and Notes

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25

The initial oxidative addition is believed to mainly occur at the C-Br bond in Pd(OAc)₂-catalyzed reaction of 1-chloro-2-bromobenzene with 2-mesitylmagniseium bromide based on the following experiments: Pd(OAc)₂-catalyzed reaction of 1,2-dichlorobenzene with 2-mesitylmagnesium bromide in THF at 60 °C gave low yield of 2,4-dimethylfluorene (24 mol%, much lower than the 95 mol% yield observed for 1-bromo-2-chlorobenzene under the same reaction condi-tions), indicating the initial oxidative addition at the C-Cl bond occurred very slowly. This observation suggested that with 1-bromo-2-chlorobenzene as substrate, the initial oxi-dative addition should mainly take place at the C-Br bond.

27

Two isomeric products in close to 1:1 ratio were always observed with unsymmetrical arynes in the reported aryne-generation strategy from o-trimethylsilylaryl triflates, see ref. 16.