Carbenes: multiplicity and reactivity Beryl X. Li December 4th, 2019 Carbenes: multiplicity and reactivity Introduction + Divalent species, similar to CO and R–CN 2p sp2 2p carbocation sp2 2p 6 C singlet carbene 2 sp Carbon 12.011 2p carbon radical sp2 – 2p triplet carbene sp2 Very reactive: cyclopropanation, dimerization, ylide carbanion formation, X–H bond insertion, among others Anslyn, E.V.; Dougherty, D.A Modern Physical Organic Chemistry, 1st ed; University Science Books, 2006. Carbenes: multiplicity and reactivity A brief history Geuther & Hermann Gomberg Doering & Knox 1954 1855 1900 1953 – CHCl3 + OH CH2N2 + CHBr3 h! – CCl2 + Cl + H2O R R Br first to propose a characterized the first synthesis of Br carbenoid intermediate example of a free radical tropolone derivatives dibromomethylene intermediate Nef common belief Lennard-Jones & Pople Duschenne & Burnelle 1897 1920s and 1930s 1951 1953 Cl N H N H H F H H and singlet H F CCl2 H necessarily triplet similar intermediate in a propose two ground states 2 Ciamician-Dennstedt linear with degenerate CF2 is sp hybridized, with for the CH carbene rearrangement p orbitals 2 a singlet ground state Hopkinson, M.N.; Richter, C.; Schedler, M; Glorius, F. Nature 2014, 510, 485–96. Fremont, P.; Marion, N.; Nolan, S.P. Coord. Chem. 2009, 253, 862–92. Carbenes: multiplicity and reactivity A brief history Fischer numerous research Arduengo 1964 1970s and 1980s 1991 W(CO)5 Ground state: OMe singlet or triplet? N N first metal-carbene mesomeric and inductive stable, isolable complex effects considered N-heterocyclic cabene Hoffman Schrock 1968 1974 present day tBu energy H Carbenes: high energy vs. gap Ta intermediate with tBu tBu tBu comprehensible reactivity 0 min. splitting energy for CH2 first synthesis of a d to have a GS singlet metal-alkylidene complex Hopkinson, M.N.; Richter, C.; Schedler, M; Glorius, F. Nature 2014, 510, 485–96. Fremont, P.; Marion, N.; Nolan, S.P. Coord. Chem. 2009, 253, 862–92. Carbenes: multiplicity and reactivity Multiplicity overview 2p Hypothetically… (as were believed in 1930s) sp degenerate 2p orbitals linear carbenes would have a triplet ground state Today, carbenes are understood to be bent… coulombic repulsion (EC) vs. sp2 – 2p energy difference (!E) Singlet-triplet splitting !GST = EC – !E 2p 2p !E 2 2 sp EC sp singlet carbene triplet carbene Baird, N.C.; Taylor, K.F. J. Am. Chem. Soc. 1978, 100 (5), 1333–8. Carbenes: multiplicity and reactivity Multiplicity overview 2p Hypothetically… (as were believed in 1930s) sp degenerate 2p orbitals linear carbenes would have a triplet ground state Today, carbenes are understood to be (mostly) bent… coulombic repulsion (EC) vs. sp2 –2p energy difference (!E) Singlet-triplet splitting !GST = EC – !E p p !E ! EC ! singlet carbene triplet carbene Baird, N.C.; Taylor, K.F. J. Am. Chem. Soc. 1978, 100 (5), 1333–8. Carbenes: multiplicity and reactivity Multiplicity overview p p "E ! ! singlet carbene triplet carbene ■ Spin quantum number (S) = 1/2 + (–1/2) = 0 ■ Spin quantum number (S) = 1/2 + 1/2 = 1 ■ Multiplicity = 2S + 1 = 1 (hence “singlet”) ■ Multiplicity = 2S + 1 = 3 (hence “triplet”) p p or or ! ! ■ Nucleophile/electrophile ■ Diradicals ■ Chelotropic reactions, stereospecific ■ Stepwise radical additions, potentially stereoselective O O 2 O CH2I2 3 N2 Zn(Cu) H2 I h! Ar Ar C Ar Ar Zn Ar Ar MeO H I MeOH Ar Ar e.g. Simmons-Smith reaction Simmons, H.E.; Smith, R.D. J. Am. Chem. Soc. 1958, 80 (19), 5323–4. Bourisson, D.; Guerret, O.; Gabbais, F.P.; Bertrand, G. Chem. Rev. 2000, 100, 39–91. Carbenes: multiplicity and reactivity Factors that determine multiplicity: parent CH2 Factors ■mesomeric interactions H ■inductive effects H–C–H p H ■hyperconjugation ∡ 102 ° ■steric effects singlet state # EC ■solvent environment Singlet-triplet splitting !GST = EC – !E coulombic repulsion (EC) vs. sp2 / 2p energy difference (!E) H H energyincreases !GST = 9 kcal/mol postive number indicates triplet H p H–C–H is lowest energy ground state H !E ∡ 137 ° # triplet state Hoffman, R. J. Am. Chem. Soc., 1968, 90, 1475–85. Baird, N.C.; Taylor, K.F. J. Am. Chem. Soc. 1978, 100 (5), 1333–8. Carbenes: multiplicity and reactivity Factors that determine multiplicity: mesomeric interactions Factors ■mesomeric interactions Mesomeric effects on carbene ground state multiplicity ■inductive effects hyperconjugation electron donating or withdrawing substituents (essentially resonance) ■ ■steric effects ■solvent environment X-type interactions Z-type interactions C-type interactions p p p ! ! ! "-electron acceptors lower/ conjugated groups lower/ "-electron donors raise p orbital unaffect #–p gap unaffect #–p gap (e.g., –NR2, –OR, –F, –Cl, –Br, –I) (e.g., carbonyls, –SO2R, –NO, –NO2) (e.g., alkenes, alkynes, aryl groups) ground state singlet ground state triplet ground state triplet Hirai, K.; Itoh, T.; Tomioka, H. Chem. Rev. 2009, 109, 3275–332. Carbenes: multiplicity and reactivity Factors that determine multiplicity: mesomeric interactions Factors ■mesomeric interactions Mesomeric effects on carbene ground state multiplicity ■inductive effects hyperconjugation electron donating or withdrawing substituents (essentially resonance) ■ ■steric effects ■solvent environment X-type interactions carbenoid species !GST p H 9 kcal/mol H ! HS –28.0 kcal/mol HS negative !GST indicates singlet is lowest energy -electron donors raise p orbital " H2N ground state –52.6 kcal/mol (e.g., –NR2, –OR, –F, –Cl, –Br, –I) H2N ground state singlet Matus, M. H.; Nguyen, M. T.; Dixon, D. A. J. Phys. Chem. A 2006, 110, 8864–71. Alder, R. W.; Blake, M. E.; Oliva, J. M. J. Phys. Chem. A 1999, 103, 11200–11. Hirai, K.; Itoh, T.; Tomioka, H. Chem. Rev. 2009, 109, 3275–332. Carbenes: multiplicity and reactivity Factors that determine multiplicity: mesomeric interactions Factors ■mesomeric interactions Mesomeric effects on carbene ground state multiplicity ■inductive effects hyperconjugation electron donating or withdrawing substituents (essentially resonance) ■ ■steric effects ■solvent environment X-type interactions Z-type interactions C-type interactions p p p ! ! ! "-electron acceptors lower/ conjugated groups lower/ "-electron donors raise p orbital unaffect #–p gap unaffect #–p gap (e.g., –NR2, –OR, –F, –Cl, –Br, –I) (e.g., carbonyls, –SO2R, –NO, –NO2) (e.g., alkenes, alkynes, aryl groups) ground state singlet ground state triplet ground state triplet Hirai, K.; Itoh, T.; Tomioka, H. Chem. Rev. 2009, 109, 3275–332. Carbenes: multiplicity and reactivity Factors that determine multiplicity: mesomeric interactions Factors ■mesomeric interactions Mesomeric effects on carbene ground state multiplicity ■inductive effects hyperconjugation electron donating or withdrawing substituents (essentially resonance) ■ ■steric effects ■solvent environment C-type interactions p " conjugated groups lower/ unaffect !–p gap aryl groups generally stabilize both the singlet state (Esub/S) (e.g., alkenes, alkynes, aryl groups) and the triplet state (Esub/T) ground state triplet Woodcock, H. L.; Moran, D.; Brooks, B. R.; Schleyer, P. v. R.; Schaefer, H. F., III. J. Am. Chem. Soc. 2007, 129, 3763–70. Hirai, K.; Itoh, T.; Tomioka, H. Chem. Rev. 2009, 109, 3275–332. Carbenes: multiplicity and reactivity Factors that determine multiplicity: inductive effects Factors ■mesomeric interactions Inductive effects ■inductive effects inductively electron-donating or -withdrawing groups intereact ■hyperconjugation selectively with carbon orbitals, which changes the !–p gap ■steric effects ■solvent environment 2p p 2p p ! ! 2s 2s !-EWG stabilizes !-nonbonding orbital !-EDG induces a smaller !–p gap, thus increasing !–p gap to favor singlet therefore favoring triplet Irikura, K.K.; Goddard III., W.A.; Beauchamp, J.L. J. Am. Chem. Soc. 1992, 114, 48–51. Hirai, K.; Itoh, T.; Tomioka, H. Chem. Rev. 2009, 109, 3275–332. Carbenes: multiplicity and reactivity Factors that determine multiplicity: hyperconjugation Factors ■mesomeric interactions Hyperconjugation ■inductive effects ■hyperconjugation Singlets, which are isoelectric with carbocations, are more stabilized ■steric effects by hyperconjugative effects compared to the radical-like triplets ■solvent environment Me Me Me Me carbenoid H Me Me Me species Me H H Me H Me Me Me !GST 9.05 kcal/mol 2.26 kcal/mol –2.47 kcal/mol –0.17 kcal/mol 2.65 kcal/mol more hyperconjugation more steric bulk (favor singlet ground state) (favor triplet ground state) Sulzbach, H. M.; Bolton, E.; Lenoir, D.; Schleyer, P. v. R.; Schaefer, H. F., III. J. Am. Chem. Soc. 1996, 118, 9908–14. Gallo, M. M.; Schaefer, H. F., III. J. Phys. Chem. 1992, 96, 1515–7. Richards, C. A., Jr.; Kim, S.-J.; Yamaguchi, Y.; Schaefer, H. F., III. J. Am. Chem. Soc. 1995, 117, 10104–7. Hirai, K.; Itoh, T.; Tomioka, H. Chem. Rev. 2009, 109, 3275–332. Carbenes: multiplicity and reactivity Factors that determine multiplicity: steric effects Factors ■mesomeric interactions Steric effects ■inductive effects Large angles favor the triplet state ■hyperconjugation Smaller angles (i.e. bulky substituents) favor the singlet state ■steric effects ■solvent environment H–C–H H H–C–H H ) ∡ 137 ° H ∡ 102 ° H ST G triplet state singlet state " singlet p triplet " relativeenergy ( H–C–H ∡ As the carbon bond angle decreases, the ! orbital gains more s character and moves lower in energy, increasing the !–p gap Sulzbach, H.M.; Bolton, E.; Lenoir, D.; Schyler, P.v.R.; Schaefer, H.F. J. Am. Chem. Soc. 1996, 118 (41), 9908–14. Hirai, K.; Itoh, T.; Tomioka, H. Chem. Rev. 2009, 109, 3275–332. Carbenes: multiplicity and reactivity