On the way towards greener transition-metal-catalyzed processes as quantified by E factors

Abstract

Transition-metal-catalyzed carbon-carbon and carbon-heteroatom bond formations are among the most heavily used types of reactions in both academic and industrial settings. As important as these are to the synthetic community, such cross-couplings come with a heavy price to our environment, and sustainability. E Factors are one measure of waste created, and organic solvents, by far, are the main contributors to the high values associated, in particular, with the pharmaceutical and fine-chemical companies which utilize these reactions. An alternative to organic solvents in which cross-couplings are run can be found in the form of micellar catalysis, wherein nanoparticles composed of newly introduced designer surfactants enable the same cross-couplings, albeit in water, with most taking place at room temperature. In the absence of an organic solvent as the reaction medium, organic waste and hence, E Factors, drop dramatically.

Keywords: E Factors; cross-coupling; green chemistry; micelles; water chemistry.

Figure 1

Structures for racemic vitamin E-based amphiphiles PTS and TPGS-750-M.

Figure 2

Appearance of a Suzuki–Miyaura reaction mixture over time, and associated work up. 1: Reagents, 2: surfactant added, 3: after 1 minute, 4: reaction complete, 5: extraxtion solvent added, 6: extraction solvent mixing, 7: extraction solvent + aqueous surfactant solution.

Figure 3

Structure and components of micelle-forming PQS.

Figure 4

PQS-based covalently bound catalysts used for metathesis and organocatalysis.

Figure 5

Structure of PQS-binap-Rh^I. binap=2,2′-bis(diphenylphosphanyl)-1,1′-binaphthyl, nbd =2,5-norbornadiene.

Scheme 1

Representative comparison of E Factors for the three named reactions. DMF =N,N-dimethylformamide, dtbpf=1,1′-bis(di-tert-butyl-phosphino)ferrocene, X-Phos=2-dicyclohexylphosphanyl-2′,4′,6′-triiso-propylbiphenyl.

Scheme 2

Impact of a single recycling of the aqueous reaction mixture on E Factors. DMA =N,N-dimethylacetamide.

Scheme 3

Comparison of E Factors from sequential cross-couplings. DavePhos=2-dicyclohexylphosphino-2′-(N,N-dimethylamino)biphenyl, TBAB =tetra-n-butylammonium bromide.

Scheme 4

E Factors from a tandem two-step, one-pot sequence.

Scheme 5

Comparison of E Factors using PQS-binap-Rh in water versus organic solvent.