OrganicOrganic ChemistryChemistry ofof LowLow--CoordinateCoordinate PhosphorusPhosphorus CompoundsCompounds

Tom Hsieh University of Toronto Organic and Biological Seminar November 12, 2007 I.I. Background:Background: MakingMaking BondsBonds AnalogousAnalogous toto CC--CC DoubleDouble BondsBonds

2 BreakingBreaking thethe ““DoubleDouble BondBond RuleRule””

Generally held belief: elements outside the first row do not form multiple bonds

Phosphaalkene chemistry deals with 3p-2p (P=C) π-bonds!!

3 CarbonCarbon--SiliconSilicon MultipleMultiple BondsBonds

ƒ 1981: West discovered Si=Si double bond C N

Si P

ƒ 1981: Brook discovered Si=C double bond

West, Fink, Michl. Science. 1981, 214, 4527. Brook, Abdesaken, Gutekunst, Gutekunst, Kallury. J. Chem. Soc., Chem. Commun. 1981, 191. 4 CarbonCarbon--NitrogenNitrogen MultipleMultiple BondsBonds

ƒ C-N bonds are ubiquitous C N

Si P

ƒ C=N and C=C double bonds are stable

ƒ Reactivity requires either: ƒ high-lying HOMOs ƒ accessible, low-lying LUMOs

ƒ π-bonds, strained rings, electron deficient species, etc.

5 UltravioletUltraviolet PhotoelectronPhotoelectron SpectroscopySpectroscopy (UPS)(UPS)

ƒ UPS determines molecular energy levels in the valence region

ƒ Helium discharge lamp is used as the photon source

ƒ Measures the kinetic energy spectra of electrons emitted by UV photons

6 UltravioletUltraviolet PhotoelectronPhotoelectron SpectroscopySpectroscopy (UPS)(UPS)

ƒ Each of the peaks in the spectrum corresponds to the - 10.30 MO energy level - 10.70 (in eV) of one valence-region He

(eV)

7 MethanimineMethanimine vs.vs. EthyleneEthylene

ƒ UV photoelectron spectroscopic measurements C N

Si P

ƒ HOMO of methanimine is the lone pair ƒ π-bond lies much lower in energy ƒ Consequently, methanimine usually reacts through its lone pair before through its π-bond

Lacombe, Gonbeau, Cabioch, Pellerin, Denis, Pfister-Guillouzo. J. Am. Chem. Soc. 1988. 110, 6064 Schmidt, Truong, Gordon. J. Am. Chem. Soc. 1987, 109, 5217. 8 CarbonCarbon andand PhosphorusPhosphorus

ƒ The P=C double bond is relatively apolar 2.5 C N ƒ Electronegativity (EN) governs an element’s ability to release or accept electrons Si P ƒ i.e. reactivity is strongly influenced by EN 2.2 ƒ σ EN of phosphorus is lower that carbon ƒ π EN of phosphorus is higher than carbon

π EN σ EN ƒ Phosphorus is a σ-electron donor & a π-electron acceptor

Waluk, Klein, Ashe III, Michl. Organometallics. 1989. 8. 2804. Le Floch. Coord. Chem. Rev. 2006. 250. 627. 9 EthyleneEthylene vs.vs. PhosphaethylenePhosphaethylene

ƒ UV photoelectron spectroscopic measurements C N

Si P

ƒ HOMO of phosphaethylene is the π-bond ƒ The lone pair lies slightly lower in energy ƒ Consequently, phosphaethylene tends to react through its π-bond before through its lone pair

Lacombe, Gonbeau, Cabioch, Pellerin, Denis, Pfister-Guillouzo. J. Am. Chem. Soc. 1988. 110, 6064 Schmidt, Truong, Gordon. J. Am. Chem. Soc. 1987, 109, 5217. 10 PhosphaylidePhosphaylide vs.vs. PhosphaalkenePhosphaalkene

ƒ Coordination number = 4 ƒ Coordination number = 2

11 II.II. SynthesisSynthesis ofof PhosphaalkenesPhosphaalkenes

12 FirstFirst IsolableIsolable PP--CC MultipleMultiple BondBond

ƒ First stable, isolable (3p-2p) π-bonded compounds

ƒ Stabilized by the delocalization of electrons

Jutzi. Angew. Chem. Int. Ed. Engl. 1975, 14, 232. 13 FirstFirst LocalizedLocalized P=CP=C DoubleDouble BondBond

ƒ 1976: Becker reports first isolable P=C compound with a localized π-bond

ƒ 1978: Bickelhaupt reports first isolable P=C compound with all-carbon substituents

Becker. Z. Anorg. Allg. Chem. 1976, 423, 242. Klebach, Lourens, Bickelhaupt. J. Am. Chem. Soc. 1978, 100, 4886. 14 CondensationCondensation StrategiesStrategies toto PhosphaalkenesPhosphaalkenes

ƒ Condensation of primary phosphines ƒ Reaction with acetals

ƒ Reaction with aldehydes

Mathey. Angew. Chem. Int. Ed. 2003, 42, 1578. 15 CondensationCondensation StrategiesStrategies toto PhosphaalkenesPhosphaalkenes

ƒ Condensation of primary phosphines ƒ Reaction with acetals

ƒ Reaction with aldehydes

Mathey. Angew. Chem. Int. Ed. 2003, 42, 1578. 16 PhosphaPhospha--OlefinationOlefination ofof CarbonylCarbonyl CompoundsCompounds

ƒ Phospha-Peterson olefination ƒ Lithium activated phosphides

ƒ Phospha-Wittig olefination

Gates. Top. Curr. Chem. 2005, 250, 107. Mathey. Angew. Chem. Int. Ed. 2003, 42, 1578. 17 PhosphaPhospha--OlefinationOlefination ofof CarbonylCarbonyl CompoundsCompounds

ƒ Phospha-Peterson olefination ƒ Base-catalyzed

ƒ Phospha-Wittig olefination

Gates. Top. Curr. Chem. 2005, 250, 107. Mathey. Angew. Chem. Int. Ed. 2003, 42, 1578. 18 PhosphaPhospha--OlefinationOlefination ofof CarbonylCarbonyl CompoundsCompounds

ƒ Phospha-Horner-Wadsworth-Emmons olefination

ƒ Phosphorylphosphine complex/reagent

ƒ Works for both aldehydes and ketone

Marinetti, Bauer, Ricard, Mathey. Organometallics. 1990, 9, 793. Mathey. Angew. Chem. Int. Ed. 2003, 42, 1578. 19 PhosphaalkenesPhosphaalkenes ViaVia MetalMetal PhosphinidenesPhosphinidenes

ƒ Schrock’s Tantalum (V) phosphinidene complex

ƒ Limited to only aldehydes

Cummins, Schrock, Davies. Angew. Chem. Int. Ed. Engl. 1993, 32, 756. 20 PhosphaalkenesPhosphaalkenes ViaVia MetalMetal PhosphinidenesPhosphinidenes

ƒ Stephan’s Zirconium (IV) phosphinidene complex

ƒ Reacts with both aldehydes and ketones

Breen, Stephan. J. Am. Chem. Soc. 1995. 117. 11914. 21 III.III. ReactivityReactivity ofof PhosphaalkenesPhosphaalkenes

22 ConsiderationsConsiderations forfor P=CP=C ReactivityReactivity

ƒ Small ΔE between the

P=C π and nP orbitals ƒ Interference of lone pair ƒ Metal-coordination ƒ Quaternization at phosphorus centers is slow and difficult ƒ Polarity of the P=C bond can be reversed ƒ Alters the reactivity of P=C

Mathey. Angew. Chem. Int. Ed. 2003, 42, 1578. 23 ConsiderationsConsiderations forfor P=CP=C ReactivityReactivity

ƒ Small ΔE between the

P=C π and nP orbitals ƒ Interference of lone pair ƒ Metal-coordination ƒ Quaternization at phosphorus centers is slow and difficult ƒ Polarity of the P=C bond can be reversed ƒ Alters the reactivity of P=C

Mathey. Angew. Chem. Int. Ed. 2003, 42, 1578. 24 HydrogenationHydrogenation andand EpoxidationEpoxidation ofof P=CP=C

ƒ Lone pair interferes with these reactions so coordination

with W(CO)5 is necessary otherwise no reaction ƒ Catalytic hydrogenation with metal-complexes

ƒ Epoxidation with m-CPBA

Vaumas, Marinetti, Mathey. J. Organomet. Chem. 1991, 413, 41. Bauer, Marinetti, Ricard, Mathey. Angew. Chem. Int. Ed. Engl. 1990, 29, 1166. 25 RegioselectiveRegioselective HydrometalationHydrometalation ofof P=CP=C

ƒ Lone pair does not interfere with these reactions ƒ Hydrostannation

ƒ Hydrozirconation

Schmitz, Leininger, Bergstrasser, Regitz.. Heteroat. Chem. 1998, 9, 453. Dufour, Caminade, Basso-Bert, Igau, Majoral. Organometallics. 1992, 11, 1131. 26 PP--HeterocyclesHeterocycles viavia CycloadditionsCycloadditions

ƒ [2+1] – P=C to chlorocarbenes

ƒ [2+3] – P=C to 1,3-dipole compounds ƒ results in aromatic P-heterocycles

Schnurr, Regitz. Tetrahedron Lett. 1989, 30, 3951. Allspach, Regitz, Becker. Synthesis. 1986, 31. 27 DielsDiels--AlderAlder andand ElectrocyclizationElectrocyclization ofof P=CP=C

ƒ Diels-Alder – synthesis of 2-halophosphabenzenes

ƒ 4π conrotatory electrocyclization

Mathey. Angew. Chem. Int. Ed. 2003, 42, 1578. Marinetti, Ricard, Mathey. Organometallics. 1990, 9, 788. 28 [3,3][3,3] SigmatropicSigmatropic RearrangementRearrangement

ƒ Phospha-Cope rearrangement

ƒ [3,3] Ring-expansion

Appel, Barth, Halstenberg. Chem. Ber. 1982, 115, 1617. Huy, Marinetti, Ricard, Mathey. Organometallics. 1992, 11, 1438. 29 AdditionAddition PolymerizationPolymerization ofof P=CP=C

ƒ Thermal, radical and anionic initiation are known ƒ Cationic initiation has yet to be reported ƒ Thermal and anionic initiation gives a regioregular polymer ƒ Radical initiation gives a regioirregular polymer

ƒ Laser-light scattering methods detect M ≈ 30,000 g/mol

Tsang, Yam, Gates. J. Am. Chem. Soc. 2003, 125, 1480. Tsang, Baharloo, Riendl, Yam, Gates. Angew. Chem. Int. Ed. 2004, 43, 5682. Noonan, Gates. Angew. Chem. Int. Ed. 2006, 45, 7271. 30 AdditionAddition CopolymerizationCopolymerization ofof P=CP=C

ƒ Block copolymers have also been synthesized via radical and anionic living polymerization

ƒ Used in Suzuki coupling reactions as phosphine ligands ƒ Isolated yields of biphenyl up to 90% ƒ Polymer/catalyst precipitates in hexanes ƒ Chromatography is not needed

Tsang, Yam, Gates. J. Am. Chem. Soc. 2003, 125, 1480. Tsang, Baharloo, Riendl, Yam, Gates. Angew. Chem. Int. Ed. 2004, 43, 5682. Noonan, Gates. Angew. Chem. Int. Ed. 2006, 45, 7271. 31 IV.IV. LowLow--CoordinateCoordinate PhosphorusPhosphorus inin HomogeneousHomogeneous CatalysisCatalysis

32 HomogeneousHomogeneous CatalysisCatalysis

ƒ Phosphorus is very prominent in modern catalysis ƒ Particularly as privileged ligands ƒ Majority are sp3-hybridized at phosphorus

33 P=CP=C inin HomogeneousHomogeneous CatalysisCatalysis

ƒ Low-coordinate-phosphorus chemistry contributes to homogeneous catalysis in two ways ƒ Low-coordinate organophosphorus species can be ligands ƒ Reactivity of low-coordinate P species can be used to prepare sp3-hybridized P ligands that are otherwise inaccessible

Mathey. Angew. Chem. Int. Ed. 2003, 42, 1578. 34 DiphosphinidenecyclobutenesDiphosphinidenecyclobutenes

ƒ Pt-catalyzed dehydrogenative silylation of ketones

ƒ Pd-catalyzed hydroamination of 1,3-dienes

Ozawa, Yamaoto, Kawagishi, Hiraoka, Ikeda, Minami, Ito, Yoshifuji. Chem. Lett. 2001, 972. Minami, Okamoto, Ikeda, Tanaka, Ozawa, Yoshifuji. Angew. Chem. Int. Ed. 2001, 40, 4501. 35 PhosphabenzenesPhosphabenzenes

ƒ Rh-catalyzed hydroformylation of alkenes

ƒ Pd-catalyzed coupling of pinacolborane

Breit, Winde, Mackewitz, Paciello, Harms. Chem. Eur. J. 2001, 7, 3106. Doux, Mezailles, Melaimi, Ricard, Le Floch. Chem. Commun. 2002, 1566. 36 AsymmetricAsymmetric Catalysis:Catalysis: NovelNovel PP--LigandsLigands

ƒ Pd-catalyzed asymmetric allylic alkylations ƒ BSA = N,O-bis(trimethylsilyl)acetamide

ƒ Pd-catalyzed asymmetric Heck reaction

Shintani, Lo, Fu. Org. Lett. 2000, 2, 3695. Ogasawara, Yoshida, Hayashi. Organometallics. 2001, 20, 3913. Gilbertson, Genov, Rheingold. Org. Lett. 2000, 2, 2885. 37 CrossCross--CouplingCoupling withwith P=CP=C LigandsLigands

ƒ Suzuki cross-coupling

ƒ Sonogashira cross-coupling reactions

Deschamps, Le Goff, Ricard, Le Floch. Heteroat. Chem. 2007, 18, 363. 38 ConclusionsConclusions

ƒ P=C and C=C are quite similar with regards to ƒ Bonding, polarity ƒ Methods of preparation ƒ Reactivity

ƒ P=C proves to be efficient ligands in catalysis ƒ Early stages of development shows promise

39 Phosphorus:Phosphorus: TheThe CarbonCarbon CopyCopy

ƒ Consider replacing a CR fragment with a P moiety

Becker. Z. Anorg. Allg. Chem. 1976, 423, 242.; Becker, Gresser, Uhl. Z.Naturforsch. B. 1981, 36, 16.; Hitchcock, Lappert, Leung. J. Chem. Soc., Chem. Commun. 1987, 1282.; Gates. Top. Curr. Chem. 2005, 250, 107. 40 Phosphorus:Phosphorus: TheThe CarbonCarbon CopyCopy

“To fully realize what (phospha-organic) chemistry means, it is only necessary to imagine what would be left of organic chemistry if alkenes, alkynes and carbenes did not exist.”

- Francois Mathey -

41 AcknowledgementsAcknowledgements

ƒ Prof. Vy M. Dong ƒ Dr. Mandy Yam ƒ Dong Group: Dr. Yang Li Dr. Zengming Shen Matthew Coulter Charles Yeung Angelica Rojas Hasan Khan Thi Phan Marc Tremblay Wilmer Alkhas Photo Credit: Wilmer Alkhas

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