Decarboxylative Phosphine Synthesis: Insights into the Catalytic, Autocatalytic, and Inhibitory Roles of Additives and Intermediates

Abstract

Phosphines are among the most widely used ligands, catalysts, and reagents. Current synthetic approaches to phosphines are dominated by nucleophilic displacement reactions with organometallic reagents. Here, we report a radical-based approach to phosphines that proceeds by a cross-electrophile coupling of chlorophosphines and redox-active esters. The reaction allows for the synthesis of a broad range of substituted phosphines that were not readily attainable with the present methods. Our experimental and DFT computational studies also clarified the catalytic, autocatalytic, and inhibitory roles of additives and intermediates, as well as the mechanistic details of the photocatalytic and zinc-mediated redox modes that can have implications for the mechanistic interpretation of other cross-electrophile coupling reactions.

Manganese-mediated reductive functionalization of activated aliphatic acids and primary amines

“…Without optimization of the reaction conditions, the desired phosphine product could be obtained, but in much less efficiency than Larionov’s zinc protocol (Fig. 9c, d ) 41 .

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“…The crosscoupling was successful for various primary, secondary, and tertiary aliphatic NHPI esters, including those containing heterocyclic alkyl groups (3, 6-22, 30-35), cyclic alkyl group (23-26, 43, 44) and acyclic alkyl groups (27)(28)(29). Primary NHPI ester with α-oxygen substitution was also tolerated and afforded the desired product (41). The corresponding carboxylic acids and the decarboxylative hydrogenated alkanes were found to be the major byproducts for the low-yielding cases.…”

“…Sun et al successfully employed gem-difluoroalkenes as electrophile in a zinc-mediated decarboxylative alkenylation of RAEs 40 . Very recently, Larionov developed a decarboxylative phosphine synthesis from RAEs and chlorophosphines with Zinc as stoichiometric reductant and PMDTA (N,N,N′,N″,N″-pentamethyldiethylenetriamine) as additive 41 . Despite these exquisite progresses, the development of new method for more types of carbon-heteroatom and carbon-carbon bond formation is still highly desirable.…”

Phosphorylation of Carboxylic Acids and Their Derivatives with P(O)–H Compounds Forming P(O)–C Bonds

“…Pre-activating the acids with N-hydroxyphthalimide (NHPI) and then coupling the resulting esters with R 2 PCl under zinc-mediated and photocatalytic reaction conditions produced phosphines. 10 However, the relatively harsh reaction conditions used resulted in low functional group tolerance and this narrows the application of this method in organic synthesis. -Amino acids are naturally available and they and their derivatives can decarboxylatively couple with a variety of nucleophiles, such as organohalides, terminal alkynes, active heteroarenes, thiols, and alcohols, and this greatly facilitates the synthesis of related -amino functionalized molecules.…”

Versatile Visible‐Light‐Driven Synthesis of Asymmetrical Phosphines and Phosphonium Salts

“…[10] While sometimes very effective,t hese reactions can only be used to introduce alkyl substituents with a b-H atom, and often suffer from issues of regioselectivity.V ery recently,r adicalc ross-coupling of N-hydroxyphthalimide esters with chlorophosphines was reported,m ediated either by am etal reductant (Zn) or an iridiump hotocatalyst. [11] While this protocol provided ab road range of tertiary phosphines, pre-functionalization steps were required to obtain the activated esters, which limits the attractivenessoft hese reactions.…”