1. Chapter 7 Organometallics: Group I & II
Advanced Org Chem-Carey B
Fall 2002
Chapter 7 Organometallics: Group I & II
Grignard reagents: RMgX  Rd--d+MgX; X = I > Br > Cl
preparation: Rd+-Xd- + Mgo  RMgX in ether or THF
commercially available: R = Me, Et, Ph, allyl, vinyl, benzyl
less reactive vinyl/aryl halides made in more basic THF
activated Mg0: I2, (CH2X)2, MgX2 with Na0/K0
formation mechanism: SET from Mg0;  621 top
aryl/vinyl/cyclopropyl halides: dianions;  622 top
5-ring from 5-hexenyl bromide and Mg0: radical intermediates
racemization except cyclopropyl & vinly Grignards
Schlenk equilibrium in solution:  623 middle
monomeric or dimeric complexes with solvents:  624 Fig. 7.1
factors: concentration, solvent, types of halide & R
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Chapter 7

2. Grignards: Mechanism of Formation
Advanced Org Chem-Carey B
Fall 2002
Grignards: Mechanism of Formation
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Chapter 7

3. Organolithium Reagents (I)
Advanced Org Chem-Carey B
Fall 2002
Organolithium Reagents (I)
Preparation: Rd+-Xd- + 2 Lio  Rd-Lid+ + LiX
radical transfer: naphthalene, DTBB, LDMAN;  625 top
reduction of sulfides: a-lithio ethers/sulfides;  625 middle
aggregate structure in solvation:  626 Fig. 7.2
higher aggregates in hydrocarbons, lower aggregates in ethers & monomers in strong donor solvents (TMEDA, HMPA, DMPU)
Deprotonation: hydrogen-metal exchange
acidity of hydrogens:  627 bottom
directing (chelating) groups:  629 Scheme 7.1
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Chapter 7

4. Organolithium Reagents: Preparation (II)
Advanced Org Chem-Carey B
Fall 2002
Organolithium Reagents: Preparation (II)
Preparation with RLi: BuLi < s-BuLi < t-BuLi
directed a-metallation: chelating donor groups:  630 top
b-metallation with amides:  631 top
without directing groups: BuLi & KOtBu;  631 bottom
halogen-metal exchange: 2 eq. RLi;  632 top
toward more stable alkenyl/aryllithiums:  633 Scheme 7.2
high degree of retention: vinyl & cyclopropyl lithiums
metal-metal exchange: vinyl-SnR3;  634 top
retention of chiral carbanions:  634 bottom
vinyl lithium from the Shapiro reaction:  631 middle
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Chapter 7

5. Alkylation Reactions of RLi & RMgX
Advanced Org Chem-Carey B
Fall 2002
Alkylation Reactions of RLi & RMgX
RLi: competing with e--transfer & elimination
good yields: 1o iodides with HMPA;  635 top
delocalized RLi: high degree of inversion;  635 middle
alkenyllithiums: retention of configuration;  635 middle
allylic halides: good yields with mostly SN2’;  635 bottom
1,3-/1,4-/1,5-diiodides: 3-/4-/5-rings;  636 top
R3SiX/R3SnX + R’Li  R3SiR’/R3SnR’
RMgX: less reactive than RLi;  636 bottom
good with reactive E+: MeX, allyl-X, BnX, R-SO3-R’
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Chapter 7

6. Reactions of RMgX with Carbonyls (I)
Advanced Org Chem-Carey B
Fall 2002
Reactions of RMgX with Carbonyls (I)
Alcohols: additions;  639 Scheme 7.3 A-E
RCHO/RCOR’: single addition; 1o to 3o,  637 top
RCOX (X=L): double addition; 2o to 3o alcohols,  637 mid
hydride transfer: reduction with bulky substrates;  642 top
more additions: in PhH/PhMe or use of RLi;  642 middle
enolization with ROMgX: no addition reaction;  642 bot
RCO2H with CO2:  640 Scheme 7.3 section H
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7. Reactions of RMgX with Carbonyls (II)
Advanced Org Chem-Carey B
Fall 2002
Reactions of RMgX with Carbonyls (II)
Ketones or aldehydes:  Scheme 7.3 F-G
addition to R-CN: via an imine Mg salt;  637 bottom
excess R-COCl at low temp in THF:  638 top
other R-CO-X producing ketones:  640 entries 16-19
aldehydes from orthoformates:  638 middle; section F
aldehydes from formamides:  638 bottom
Barbier reaction: in-situ formation & reaction;  644 middle
Isomerization: allyl/homoallyl-MgX;  643 top
no equilibrium in the 5-hexenyl system:  643 bottom
Amines by addition to imines:  640 Scheme 7.3 I
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8. Reactions of RLi with Carbonyls
Advanced Org Chem-Carey B
Fall 2002
Reactions of RLi with Carbonyls
Similar reactivity to RMgX:  Scheme 7.4 A-E
a,b-Enones: 1,2- vs 1,4-addition;  644 bottom
highly reactive RLi vs catalytic amount of HMPA (Cu+1)
Ketones from RCO2H:  645 top & entries 11-13
better yields with TMSCl: reduced carbinols;  645 middle
unsymmetrical ketones with CO2: tandem;  645 middle
acid chlorides/anhydrides:  647 entries 14 & 15
from amides: Weinreb amides;  645 bottom
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Chapter 7

9. Addition of RLi: Synthesis of Ketones
Advanced Org Chem-Carey B
Fall 2002
Addition of RLi: Synthesis of Ketones
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Chapter 7

10. Addition to Carbonyls: Stereochemistry
Advanced Org Chem-Carey B
Fall 2002
Addition to Carbonyls: Stereochemistry
Steric bias: equatorial approach;  648 middle
increased selectivity with added salts: LiClO4
Acyclic carbonyls: Cram’s rule;  648 bottom
chelation control: a-alkoxylketones/aldehydes;  649 mid
Enantioselective addition:  649 bottom
Mg salt of TADDOL: chiral additive (stoichiometric)
lower ee for saturated alkyl ketones
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Chapter 7

11. Chelation Control in Addition to Carbonyls
Advanced Org Chem-Carey B
Fall 2002
Chelation Control in Addition to Carbonyls
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12. Organozinc Compounds: R2Zn & RZnX
Advanced Org Chem-Carey B
Fall 2002
Organozinc Compounds: R2Zn & RZnX
Less e--positive Zn: less nucleophilic than RMgX/RLi
Preparation: ZnX2 + 2 RLi/RMgX  R2Zn
one-pot process: sonication of [RX + Mg0 + ZnCl2]
RX + activated Zn0 (Rieke method) or Zn-Cu:  650 bottom
metal-halogen exchange: functionalized R;  651 middle
efficient catalysis by MnBr2, CuCl or Ni(acac)2:  651 bottom
zinc-boron exchange: R2Zn-BR’3;  652 top & middle
stereoselective synthesis: retention;  652 middle
addition to alkynes by catalysts: alkenylzinc;  652 bottom
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13. Reactions of Organozinc Compounds
Advanced Org Chem-Carey B
Fall 2002
Reactions of Organozinc Compounds
Addition to carbonyls: less effective with ketones
activation with MgX2: catalysis with Ti(i-OPr)4 or TMSCl
promoted addition with TMSCl:  653 top
addition to acyl chlorides:  657 top
enantioselective addition to aldehydes:  656 middle
chelation control by chiral amino alcohols:  653 bottom
Reformatsky reaction:  657 bottom &  660 Scheme 7.5
‘zincates’: more reactive; [Li]/[Mg],  659 bottom
olefination of ketone/ester: alkene/enol ether;  661 middle
Lombardo’s reagent: Zn, CH2Br2 & TiCl4 :  661 middle
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14. Organocadmium Compounds
Advanced Org Chem-Carey B
Fall 2002
Organocadmium Compounds
Preparation: CdX2 + 2 RLi/RMgX  R2Cd
RX + activated Cd0 (Rieke method) from CdX2:  661 bot
Less e--positive Cd: similar reactivity to [Zn]
synthesis of ketones from acyl chlorides:  662 top
toxic cadmium compounds!!
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15. Organomercury Compounds
Advanced Org Chem-Carey B
Fall 2002
Organomercury Compounds
Preparation: HgX2 + 2 RLi/RMgX  R2Hg
oxymercuration: functionalized R;  294-8
boron-Hg exchange: 1o alkyl groups;  662 bottom
alkenylmercury: from hydroboration of alkynes;  662 bottom
Weakly nucleophilic: reactive E+;  663 top
no reactions with aldehydes/ketones
reactions of alkenylmercuries with acid chlorides
addition activated by Lewis acids to alkenes:  663 middle
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16. Organoindium Compounds
Advanced Org Chem-Carey B
Fall 2002
Organoindium Compounds
Easier to be oxidized than Mg: efficient e- donors
allylic halide + aldehydes + In0:  663 bottom
cyclic TS: In(I);  664 top
reactions possible in aqueous solution:  664 middle
reactions with functionalized substrates:  664 middle
chelated TS with a-donor substituents
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Chapter 7

17. Organocerium Reagents
Advanced Org Chem-Carey B
Fall 2002
Organocerium Reagents
Preparation: CeCl3 + RLi/RMgX  RCeCl2 + LiCl
efficient addition to carbonyls with acidic a-protons/sterically hindered ketones: anhydrous CeCl3 required;  665 mid
retention of strong nucleophilicity & reduced basicity
catalytic CeCl3 (5-10 mol%): better yields;  665 bottom
efficient addition to carboxylates: 2 CeCl3;  666 top
addition to amides: ketones;  666 middle
excellent reactivity for nitriles & imines:  666 middle
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Chapter 7