1. Chapter 8 Organotransition Metals
Advanced Org Chem-Carey B
Fall 2002
Chapter 8 Organotransition Metals
Catalytic process & oxidation state changes at metals
Organocopper Intermediates
History: catalytic effect for 1,4-addition of Grignards:  676 top
Preparation: n RLi + m CuX;  676 middle
Me2CuLi: dimeric in solution ( 676 bot) & monomeric with LiI
mixed cuprates with two different ligands:  678 Table 8.1
faster transfer of the valuable ligand over the other cheap ligand
higher-order cyanocuprates: more stable;  679 top
mixed cyanocuprates with 2-thienyl:  679 middle
‘Modern Organocopper Chemistry’: Ed. N. Krause, Wiley, 2002
Carey B-Chap 8-5ed
Chapter 8

2. Organocopper: History & Preparation
Advanced Org Chem-Carey B
Fall 2002
Organocopper: History & Preparation
‘cuprates’
Carey B-Chap 8-5ed
Chapter 8

3. Organocopper Reagents: Preparation
Advanced Org Chem-Carey B
Fall 2002
Organocopper Reagents: Preparation
Mixed cyanocuprates by metal-metal exchange
Li-Zr/Sn: alkenyl group transfer over Me;  679 bottom
FG-RCuX  FG-RX + Cu* (activated)
Cu* from reduction of CuI•PBu3 by Li-naphthalenide
use of CuCN & LiCl:  680 top
many FGs tolerant: nitro, cyano, ester, carbamate
Reliable Cu(I): CuI, CuCN, CuBr-SMe2
Carey B-Chap 8-5ed
Chapter 8

4. Reactions of Organocopper Reagents (I)
Advanced Org Chem-Carey B
Fall 2002
Reactions of Organocopper Reagents (I)
Substitution: soft Nu; R-X/R-OTs;  684 Scheme 8.1
effective even with aryl/alkenyl halides:  680 bottom
mechanism: oxidative addition / reductive elimination;  681 top
inversion with 2o R-Br/-OTs vs racemization with 2o R-I
stereochem: SN2 or SN2’ (major with RCu-BF3);  681 mid
reaction dependent: solvent, CuX;  681 bottom &  682 top
allylic acetates: SN2’ with inversion;  682 middle &  682 bot
d-alkoxy allylic acetates: anti;  683 top
more reactive a-keto halides than 1o halides:  683 bottom
propargylic acetate/halides/sulfonates: allenes;  683 bottom
Carey B-Chap 8-5ed
Chapter 8

5. Reactions of Organocopper Reagents (II)
Advanced Org Chem-Carey B
Fall 2002
Reactions of Organocopper Reagents (II)
Epoxide opening: less hindered carbon;  685 top
stereoselective: SN2 reactions;  685 middle
vinylic epoxides: rearrangement; allylic alcohols;  685 bot
Cu-catalyzed reactions:  692 Scheme 8.4
alkylations:  691 bottom & 693 top
entry 7: allylic chloride vs allylic acetate
mechanism: fast metal-metal exchange;  693 middle
conjugate additions: enones & enoates; Scheme 8.4 (B)
Carey B-Chap 8-5ed
Chapter 8

6. Cu-Catalyzed Reactions (II): Mechanism
Advanced Org Chem-Carey B
Fall 2002
Cu-Catalyzed Reactions (II): Mechanism
Carey B-Chap 8-5ed
Chapter 8

7. Conjugate Addition of Organocoppers
Advanced Org Chem-Carey B
Fall 2002
Conjugate Addition of Organocoppers
1,4-Addition to enones:  689 Scheme 8.2
mechanism: RDS = reductive elimination;  687 top
best Cu catalysts: CuBr-SMe2, CuCN
activation by TMSCl (HMPA), TMSCN or PR3:  686 middle
active combination: BF3•Et2O : RLi : CuCN = 1 : 1 : 1
greatly improved yields for a,b-unsaturated esters & amides
RCu•BF3: more reactive toward conjugated ester & nitriles
Tandem alkylations: usually trans;  691 Scheme 8.3
Carey B-Chap 8-5ed
Chapter 8

8. 1,4-Addition to Enones: Mechanism
Advanced Org Chem-Carey B
Fall 2002
1,4-Addition to Enones: Mechanism
RDS: reductive elimination step
by isotope labeling
Carey B-Chap 8-5ed
Chapter 8

9. Mixed Cu-Zn reagents: Mild Nucleophiles
Advanced Org Chem-Carey B
Fall 2002
Mixed Cu-Zn reagents: Mild Nucleophiles
Useful for conjugate addition:  696 Scheme 8.5
SN2’ of allylic halides & addition to aldehydes with BF3
preparation: FG-RZnX + CuCN•2LiCl  FG-RCu(CN)ZnX
weakly basic & many FGs compatible: FG = CO2R, CN, COR, NHCO, NH2, Cl, Br, Si(OR)3, SOnR, P(O)(OR)2, CCH
catalytic process: catalytic Cu & stoichiometric Zn;  694 bot
Enantioselective addition: chiral ligands;  703 top
mixed cuprates: [RCuL]Li, L= chiral ligands;  702 – 703
chiral ligands for a catalytic process:  704 Scheme 8.7
Carey B-Chap 8-5ed
Chapter 8

10. Reactions of Organocoppers
Advanced Org Chem-Carey B
Fall 2002
Reactions of Organocoppers
1,4-Addition to alkynyl esters: facile;  697 bottom
syn addition of cuprates & tandem a-alkylations possible
Mixed Cu-Mg (Normant) reagents:  695 bottom
syn addition: regiospecificity for 1,1-alkenes;  697 top
mixed Cu-Zn reagents with 1-alkynes:  697 middle
tandem substitution reactions:  698 Scheme 8.6
Ullman coupling: e--poor biaryl coupling;  705 top
unsymmetrical coupling: oxidation of cuprates;  705 middle
Carey B-Chap 8-5ed
Chapter 8

11. Organopalladium Intermediates
Advanced Org Chem-Carey B
Fall 2002
Organopalladium Intermediates
Pd-catalyzed substitution: p-complexes;  707 top
Wacker reaction: ethylene to acetaldehyde;  709 middle
catalytic cycle with Pd2+ & Cu2+: O2 as an oxidant;  709 bottom
electrophilic cyclization & b-H elimination:  711 –  712
Pd-catalyzed alkylation: p-allyl complexes;  707 mid
with more stabilized carbanions as a Nu:  713 top
medium to large-rings: removal of the sulfonyl;  714 middle
external Nu – retention vs internal Nu – inversion:  713 bot
enantioselective allylations: chiral ligands;  715 Scheme 8.8
Carey B-Chap 8-5ed
Chapter 8

12. Pd-Cat. Nucleophilic Substitution: p-Complexes
Advanced Org Chem-Carey B
Fall 2002
Pd-Cat. Nucleophilic Substitution: p-Complexes
Carey B-Chap 8-5ed
Chapter 8

13. Wacker Reaction: General
Advanced Org Chem-Carey B
Fall 2002
Wacker Reaction: General
catalytic
‘unsupported mechanism’
Carey B-Chap 8-5ed
Chapter 8

14. Wacker Reaction: Mechanism (unsupported)
Advanced Org Chem-Carey B
Fall 2002
Wacker Reaction: Mechanism (unsupported)
Carey B-Chap 8-5ed
Chapter 8

15. Wacker Reaction: Mechanism (proven)
Advanced Org Chem-Carey B
Fall 2002
Wacker Reaction: Mechanism (proven)
Carey B-Chap 8-5ed
Chapter 8

16. Pd-Catalyzed Alkylations: p-Allyl Complexes
Advanced Org Chem-Carey B
Fall 2002
Pd-Catalyzed Alkylations: p-Allyl Complexes
Carey B-Chap 8-5ed
Chapter 8

17. Pd-Catalyzed Coupling Reactions
Advanced Org Chem-Carey B
Fall 2002
Pd-Catalyzed Coupling Reactions
Heck reaction: substitution of alkenes;  718 top
with alkenyl/aryl halides/sulfonates: mechanism;  717 mid
alkyl halides with b-H not suitable due to facile b-H elimination
I > Br  OTf >> Cl: Ph4P+Cl- ( 718 top), P(tBu)3 for chlorides
activation: Ag+2, NaHCO3/Na2CO3 with PTC, R4N+X-, NiBr2
Pd(0): Pd(PR3)4 or Pd(OAc)2/PdCl2 with R3N & PR3
preferred PR3: diphosphines ( 716), P(o-tolyl)3, P(2-furyl)3
regioselectivity: b for e--poor alkenes, a with bidentate ligands (dppe, dppp) & triflates ( 505 (5ed)), allyl silanes ( 720 top)
stereoselectivity: E & retention;  Scheme 8.9
Carey B-Chap 8-5ed
Chapter 8

18. Heck Reactions: Catalytic Mechanism
Advanced Org Chem-Carey B
Fall 2002
Heck Reactions: Catalytic Mechanism
Neutral pathway:
oxidative
addition
reductive
elimination
syn-elimination
syn-insertion
internal rotation
Carey B-Chap 8-5ed
Chapter 8

19. Diphosphines in Pd-Catalyzed Couplings
Advanced Org Chem-Carey B
Fall 2002
Diphosphines in Pd-Catalyzed Couplings
Carey B-Chap 8-5ed
Chapter 8

20. The Heck Reaction: Ionic Mechanism (II)
Advanced Org Chem-Carey B
Fall 2002
The Heck Reaction: Ionic Mechanism (II)
Ionic pathway:
elimination
Carey B-Chap 8-5ed
Chapter 8

21. Pd-Catalyzed Cross Coupling (I)
Advanced Org Chem-Carey B
Fall 2002
Pd-Catalyzed Cross Coupling (I)
Cross coupling: alkenyl/aryl halides & organometallics
similar mechanism to Heck reactions:  723 bottom
organometallics: RMgX, RLi ( 724 top), RZnX ( 724 bot)
Negishi coupling (RZnX): dppf;  725 Scheme 8.10 entry 7
enolates/enol ethers as organometallics:  728 – 730
1-alkynes with Cu(I): various bases;  726 middle
Sonogashira coupling:  727 Scheme 8.11
aryl/alkenyl-SnR3: Stille coupling;  Scheme
increased rates: TFP/AsPh3 & Cu(I) co-catalyst;  731 – 734
tolerant to FGs: alcohol, ester, nitrile, nitro, cyano, alkoxy
order of transfer: alkynyl > alkenyl > aryl > methyl > alkyl
successful coupling of 1o halides:  735 top
acylations with acyl halides: ketone products;  736 bottom
Carey B-Chap 8-5ed
Chapter 8

22. Cross-coupling via Transmetallation
Advanced Org Chem-Carey B
Fall 2002
Cross-coupling via Transmetallation
M = Na, Mg, Zn, B, Al, Zr, Sn, Si; Ar’ = R (Ar), H, M’R
oxidative
addition
reductive
elimination
transmetallation
TranMetal-Chap3
Chapter 8

23. Pd-Catalyzed Cross Coupling (II)
Advanced Org Chem-Carey B
Fall 2002
Pd-Catalyzed Cross Coupling (II)
Cross coupling: alkenyl/aryl halides & organometallics
aryl/alkenyl-BR2: Suzuki coupling;  Scheme 8.14
R = OH, OR’, R’: base-catalyzed mechanism; Cs2CO3, TlOH
mild, green & compatible with many FGs:  740 top
coupling of sp3 alkyl groups with 9-BBN:  742 top &  741 mid
Carbonylations: mechanism;  753 Scheme 8.15
halides & organometallics with CO: ketones;  752 middle
hydrocarbonylation: a-arylpropionic acids;  749 – 750
lactones ( 752 mid), amino acids & Heck reaction ( 752 bot)
solvocarbonylation: b-alkoxy acids;  750 bot – 751 top
Carey B-Chap 8-5ed
Chapter 8

24. Carbonylations: Organometallics & Halides
Advanced Org Chem-Carey B
Fall 2002
Carbonylations: Organometallics & Halides
Carey B-Chap 8-5ed
Chapter 8

25. Carbonylations of Alkenes: Mechanism
Advanced Org Chem-Carey B
Fall 2002
Carbonylations of Alkenes: Mechanism
Carey B-Chap 8-5ed
Chapter 8

26. Hydrocarbonylations: Acid Derivatives (I)
Advanced Org Chem-Carey B
Fall 2002
Hydrocarbonylations: Acid Derivatives (I)
Carey B-Chap 8-5ed
Chapter 8

27. Ni-Catalyzed Cross Coupling
Advanced Org Chem-Carey B
Fall 2002
Ni-Catalyzed Cross Coupling
Cross coupling of allylic halides:  755 top
p-allyl complex: mechanism; Ni(I), Ni(II), Ni(III);  756 bottom
more reactive than Pd(0): Ar-Cl, Ar-OMe, Ar-OMs, Ar-OP(O)OR2
less b-H elimination but caution!!! extremely toxic Ni(CO)4
Ni(COD)2 or Ni(PPh3)4: aryl/alkenyl/allylic halides;  755 bot
in-situ generation of Ni(0) with Zn(0)/RMgX:  756 middle
Ni(dppe)Cl2 with alkyl-MgBr:  757 top
isomerization of 2o to 1o alkyl Grignards:  (5th ed) 528 bot
cross coupling with other organometallics:  758 – 759
Carey B-Chap 8-5ed
Chapter 8

28. Ni-Catalyzed Coupling: Mechanism
Advanced Org Chem-Carey B
Fall 2002
Ni-Catalyzed Coupling: Mechanism
Carey B-Chap 8-5ed
Chapter 8

29. [Rh] & [Co]-Catalyzed Coupling Reactions
Advanced Org Chem-Carey B
Fall 2002
[Rh] & [Co]-Catalyzed Coupling Reactions
Hydroformylation (oxo reaction): [Rh];  759 bottom
cyclic amides/esters with internal Nu: (N/O):  760 middle
Fischer-Tropsch process:  760 bottom
preparation of hydrocarbons from syn gas, [CO + H2]
decarbonylation reversible: RCHO & RCOCl;  761 top
Co-catalyzed coupling: RMgX & RZnX;  761 middle
good donor solvents required as a co-catalyst: NMP, DMPU
Carey B-Chap 8-5ed
Chapter 8

30. Carbonylation & Fischer-Tropsch Process
Advanced Org Chem-Carey B
Fall 2002
Carbonylation & Fischer-Tropsch Process
Carey B-Chap 8-5ed
Chapter 8

31. Decarbonylation of RCHO & RCOCl
Advanced Org Chem-Carey B
Fall 2002
Decarbonylation of RCHO & RCOCl
Wilkinson catalyst
Carey B-Chap 8-5ed
Chapter 8

32. Olefin Metathesis Reactions
Advanced Org Chem-Carey B
Fall 2002
Olefin Metathesis Reactions
Alkylidene exchange betweem two olefins:  761 bot
mechanism: metal-carbene/metallocyclobutane;  762 top
alkylidene catalysts: ‘Grubbs catalysts’;  762 middle
intramolecular (RCM):  762 &  766 Scheme 8.16 entry 8
cross-metathesis: relative reactivity of olefins;  763 bottom
Metathesis of enynes: conjugated dienes;  764 top
intramolecular: vinylcycloalkenes;  764 middle
silyoxyalkynes: acetylcycloalkenes: ;  764 bot – 765 top
Metathesis of diynes: [Mo]/[W]:  765 middle
Carey B-Chap 8-5ed
Chapter 8

33. Olefin Metathesis (I): General
Advanced Org Chem-Carey B
Fall 2002
Olefin Metathesis (I): General
Carey B-Chap 8-5ed
Chapter 8

34. Olefin Metathesis (II): Mechanism
Advanced Org Chem-Carey B
Fall 2002
Olefin Metathesis (II): Mechanism
Carey B-Chap 8-5ed
Chapter 8

35. Olefin Metathesis: Catalysts
Advanced Org Chem-Carey B
Fall 2002
Olefin Metathesis: Catalysts G F I H
1st generation
2nd generation
Carey B-Chap 8-5ed
Chapter 8

36. Olefin Metathesis of Enynes: Mechanism
Advanced Org Chem-Carey B
Fall 2002
Olefin Metathesis of Enynes: Mechanism
Carey B-Chap 8-5ed
Chapter 8

37. Organometallics with p Bonding
Advanced Org Chem-Carey B
Fall 2002
Organometallics with p Bonding
Metal bonding to p bonds: back-bonding;  767 bot
formation: exchange with ligands at metal;  767 – 768
formation of p-allyl complexes of Ni:  768 middle
ferrocene: stable, neutral, e--rich aromatics;  768 bottom
other p-organometallics with Cp: EAN rule;  769 middle
cyclobutadiene complexes: stable;  769 Scheme 8.17
Cr complexes of arenes: preparation;  769 bottom
e--poor arenes: acidic H & SN reactions;  770 middle
h5-cyclohexadienyl anions with no leaving group:  770 bot
Carey B-Chap 8-5ed
Chapter 8

38. Metal Bonding to p Bonds
Advanced Org Chem-Carey B
Fall 2002
Metal Bonding to p Bonds
back-bonding
Carey B-Chap 8-5ed
Chapter 8

39. p Complexes of Transition Metals
Advanced Org Chem-Carey B
Fall 2002
p Complexes of Transition Metals
Carey B-Chap 8-5ed
Chapter 8

40. Cp Complexes of Transition Metals
Advanced Org Chem-Carey B
Fall 2002
Cp Complexes of Transition Metals
Carey B-Chap 8-5ed
Chapter 8