Ligands for Palladium‐Catalyzed Cross‐Couplings of Alkyl Halides: Use of an Alkyldiaminophosphane Expands the Scope of the Stille Reaction

Abstract

Dedicated to Professor Manfred T. Reetz on the occasion of his 60th birthdayWhereas nickel-and palladium-catalyzed methods for crosscoupling aryl and vinyl halides and sulfonates with a range of organometallic reagents have reached a fairly high level of sophistication, [1] comparable progress has not yet been achieved for reactions of alkyl halides and sulfonates.[2]Recently, we and others have begun to address this shortcoming by describing catalysts for certain Suzuki, [3] Negishi, [4,5] Kumada, [6,7] Stille, [8] and Hiyama [9] couplings of primary alkyl electrophiles. With the exception of Suzuki's observation that [Pd(PPh 3 ) 4 ] effects cross-couplings of alkyl iodides with R-(9-BBN), [3a] the palladium-based catalysts that were reported for coupling alkyl electrophiles have all employed a hindered trialkylphosphane (PCy 3 or P(tBu) 2 Me) as the ligand.To increase the likelihood of expanding the still-limited scope of cross-couplings of alkyl electrophiles, we have been exploring the use of new classes of ligands for these processes. Herein, we establish that, in the presence of alkyldiaminophosphanes (PR(NR' 2 ) 2 ), we can accomplish palladiumcatalyzed Stille cross-couplings of alkyl bromides and iodides not only with vinyl stannanes, but also with aryl stannanes [Eq. (1)], a class of reaction partners that are not efficiently coupled by Pd/PR 3 (PR 3 = trialkylphosphane).As a consequence of the electron-richness and the ready accessibility of alkyldiaminophosphanes (PR(NR' 2 ) 2 ), [10] we

Selective Formation of a Trisubstituted Alkene Motif by trans‐Hydrostannation/Stille Coupling: Application to the Total Synthesis and Late‐Stage Modification of 5,6‐Dihydrocineromycin B

“…[34] Structural as well as spectroscopic data suggest that the chloride ligand engages in hydrogen bonding,w hich aligns and locks the alkyne within the coordination sphere of the catalyst. [35,36] Instead, indirect solutionsp revail in the literature,i nw hich an alkenylstannane is first converted into the corresponding iodide,which is then treated with astoichiometric amount of Me 2 CuLi [37] or cross-coupled with an appropriate methyl donor. [34] Although the conversion of 16 into 3 by aS tille reaction with MeI (or an equivalent thereof) seemed straightforward, we were surprised to find hardly any precedent.…”

Control of the β-Hydride Elimination Making Palladium-Catalyzed Coupling Reactions more Diversified

“…In the presence of alkyldiaminophosphanes (PR(NR¢ 2 ) 2 ), Fu can accomplish palladium catalyzed Stille cross-couplings of alkyl bromides and iodides not only with Vinyl stannanes, but also with aryl stannanes. The most effective catalyst system was Pd/PCy(pyrrolidinyl) 2 [86].…”

Reduction of Secondary Alkyl Bromides by Palladium Catalysts Containing Chelating Diphosphine Ligands

“…While there has been considerable interest in expanding the scope of these reactions [5,6], success has been limited by the slow rate of oxidative addition of sp 3 hybridized alkyl halides to the palladium [7,8]. Rates are slow with methyl, slower with primary alkyl, and not detectable with secondary alkyl groups [9,10].…”