Pyridine sulfinates are stable and straightforward to prepare nucleophilic coupling partners for palladium catalyzed cross-coupling reactions with aryl and heteroaryl halides. The scope with respect to the halides coupling partner is considerable, and allows the preparation of a broad range of linked pyridines.
Heterocyclic sulfinates
are effective reagents in palladium-catalyzed
coupling reactions with aryl and heteroaryl halides, often providing
high yields of the targeted biaryl. However, the preparation and purification
of complex heterocylic sulfinates can be problematic. In addition,
sulfinate functionality is not tolerant of the majority of synthetic
transformations, making these reagents unsuitable for multistep elaboration.
Herein, we show that heterocyclic allylsulfones can function as latent
sulfinate reagents and, when treated with a Pd(0) catalyst and an
aryl halide, undergo deallylation, followed by efficient desulfinylative
cross-coupling. A broad range of allyl heteroarylsulfones are conveniently
prepared, using several complementary routes, and are shown to be
effective coupling partners with a variety of aryl and heteroaryl
halides. We demonstrate that the allylsulfone functional group can
tolerate a range of standard synthetic transformations, including
orthogonal C- and N-coupling reactions, allowing multistep elaboration.
The allylsulfones are successfully coupled with a variety of medicinally
relevant substrates, demonstrating their applicability in demanding
cross-coupling transformations. In addition, pharmaceutical agents
crizotinib and etoricoxib were prepared using allyl heteroaryl sulfone
coupling partners, further demonstrating the utility of these new
reagents.
Enantiomerically enriched [3.1.0] bicycles containing vicinal quaternary centers were synthesized from [1,6]-enynes using a cyclopentadienylruthenium catalyst containing a tethered chiral sulfoxide. The reaction was complicated by the fact that the substrates contained a racemic propargyl alcohol that could affect the selectivity of the process. Nonetheless, high levels of enantioinduction were observed, despite complications arising from the use of racemic substrates. Mechanistic studies showed that while the utilization of either enantiomer of the propargyl alcohol led to high product enantiomeric ratios when the reaction was conducted in acetone, a significant matched/mismatched effect was observed in tetrahydrofuran.
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