Site-Specific Alkene Hydromethylation via Protonolysis of Titanacyclobutanes
James A Law1, Noah M Bartfield1, James H Frederich1
1Department of Chemistry and Biochemistry, Florida State University, 95 Cheiftan Way, Tallahassee, FL, 32306, USA.
Abstract:
Methyl groups are ubiquitous in biologically active molecules. Thus, new tactics to introduce this alkyl fragment into polyfunctional structures are of significant interest. With this goal in mind, a direct method for the Markovnikov hydromethylation of alkenes is reported. This method exploits the degenerate metathesis reaction between the titanium methylidene unveiled from Cp2 Ti(μ-Cl)(μ-CH2 )AlMe2 (Tebbe's reagent) and unactivated alkenes. Protonolysis of the resulting titanacyclobutanes in situ effects hydromethylation in a chemo-, regio-, and site-selective manner. The broad utility of this method is demonstrated across a series of mono- and di-substituted alkenes containing pendant alcohols, ethers, amides, carbamates, and basic amines.
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