1. Song jin
July 10, 2010
Gong Group Meeting

3. Palladium- and Nickel-Catalyzed Coupling Reactions
＊ work in the area of palladium- and nickel-catalyzed
crosscoupling
＊ Palladium-catalyzed couplings of organometallic reagents with aryl and vinyl electrophiles (eq 1) have become classic methods for generating carbon-carbon bonds.

4. ＊ palladium-catalyzed couplings in which the halide/triflate is
sp3-hybridized are rather uncommon.
aryl and vinyl electrophiles
e.g.
unactivated alkyl electrophiles
e.g.

5. Palladium- and Nickel-Catalyzed Coupling Reactions
＊Slow oxidative addition of alkyl halides/triflates to palladium
＊Facile β-hydride elimination

6. ＊ Pd catalyzed cross-couplings of alkyl electrophiles

8. ＊no coupling occurs when anhydrous K3PO4 is employed.
＊Room-temperature
＊no coupling occurs when anhydrous K3PO4 is employed.
THF solution of B-n-hexyl-9-BBN
K3PO4·H2O (1:1),
anhydrous K3PO4
The resonance at 78 is replaced by
a signal at 4,
11B NMR spectrum does not change (78).
hydroxyl-bound “ate” complex

9. Yield:70-80%
C-Cl: 79, C-Br:66, C-I:52 (kcal/mol-1)

10. J. AM. CHEM. SOC. 2003, 125, 12527
Angew. Chem. Int. Ed. 2003, 42, 5079

11. ＊ Nickel-catalyzed Negishi cross-couplings of secondary
alkyl electrophiles

12. ＊

13. (a) The standard coupling conditions can also be applied to Negishi
Notes:
(a) The standard coupling conditions can also be applied to Negishi
reactions of activated alkyl halides. For example, n-nonylZnBr
couples with allyl bromide, benzyl bromide, and benzyl chloride
in 60, 89, and 100% yields respectively.
(b) The use of secondary organozinc reagents leads to lower yield
(c) Alkyl chlorides, alkyl tosylates, and tertiary alkyl bromides/
iodides are not suitable coupling partners.

14. ＊ Nickel-Catalyzed Negishi Cross-Couplings of Secondary Nucleophiles
with Secondary Propargylic Electrophiles at Room Temperature

15. ＊ Nickel-catalyzed Suzuki cross-couplings of secondary alkyl electrophiles
＊ For each entry, a single regio- and stereoisomer (>50:1) is observed. Our current hypothesis is that a radical intermediate may be involved.
＊ Interestingly, the reaction occurs selectively at the secondary Csp3-Br,rather than the Ar-Cl, bond.

16. ＊ These diastereoselectivities are independent of ligand structure
＊ These diastereoselectivities correlate with those observed in radical
cyclizations of these compounds, consistent with the possibility that an initially formed secondary alkyl radical cyclizes before reacting with nickel.

17. ＊ The zero-valent-ate complex undergoes a single electron transfer to a substrate to yield an anion radical of thesubstrate and cobalt(I) complex 18.
＊ we suggested that nickel-catalyzed couplings of secondary alkyl halides may proceed through the initial generation of an alkyl radical, which then combines with nickel to afford an alkylnickel complex.

18. ＊ Asymmetric nickel-catalyzed Negishi cross-couplings
of secondary alkyl halides
＊ In view of the high enantioselectivity that we observe, we believe that for this system the radical-radical coupling mechanism is unlikely to be operative.

19. ＊ this catalyst system is highly selective for coupling an R-bromo amide in the presence of either an unactivated primary or secondary alkyl bromide

20. ＊ trans-trikentrin A14 and iso-trans-trikentrin B,
both of which have been isolated from the marine sponge Trikentrion flabelliforme and exhibit antibacterial activity.
＊this indane can be prepared enantioselectively using two Negishi cross-couplings
＊ this is the first synthesis of enantioenriched
trans-1,3-dimethylindane

21. ＊ Asymmetric Negishi Cross-Couplings of Secondary Allylic Chlorides
Yield:~80%
Ee:70-98%
Yield:70-80%
Ee:~90%

23. Yield:70-80%
Ee:~90%
Yield:~80%
Ee:~90%
Negishi
Yield:~80%
Ee:~90%
organozirconium
reagents

24. ＊ Enantioselective Alkyl-Alkyl Suzuki Cross-Couplings of Unactivated Homobenzylic Halides
＊ Previous work have been limited to couplings of activated electrophiles
(e.g：allylic, benzylic, or R-halocarbonyl) with either organozinc or organosilicon reagents.

25. ＊ the chiral Ni/1 complex differentiates between the two alkyl groups (CH2Ar vs alkyl)
of the unactivated halide via a secondary interaction between the CH2Ar substituent
and the catalyst. Consistent with the suggestion that proper positioning of the
aromatic group is important for obtaining good ee,