song jin july 10, 2010 gong group meeting. palladium- and nickel-catalyzed coupling reactions *...
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Song jinJuly 10, 2010
Gong Group Meeting
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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.
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aryl and vinyl electrophiles
unactivated alkyl electrophiles
* palladium-catalyzed couplings in which the halide/triflate is sp3-hybridized are rather uncommon.
e.g.
e.g.
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* Slow oxidative addition of alkyl halides/triflates to palladium * Facile β-hydride elimination
Palladium- and Nickel-Catalyzed Coupling Reactions
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* Pd catalyzed cross-couplings of alkyl electrophiles
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* Room-temperature
* no coupling occurs when anhydrous K3PO4 is employed.
THF solution of B-n-hexyl-9-BBN
anhydrous K3PO4
11B NMR spectrum does not change (78).
K3PO4·H2O (1:1),
The resonance at 78 is replaced by a signal at 4,
hydroxyl-bound “ate” complex
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C-Cl: 79, C-Br:66, C-I:52 (kcal/mol-1) Yield:70-80%
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J. AM. CHEM. SOC. 2003, 125, 12527
Angew. Chem. Int. Ed. 2003, 42, 5079
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* Nickel-catalyzed Negishi cross-couplings of secondary alkyl electrophiles
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*
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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.
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* Nickel-Catalyzed Negishi Cross-Couplings of Secondary Nucleophiles with Secondary Propargylic Electrophiles at Room Temperature
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* Nickel-catalyzed Suzuki cross-couplings of secondary alkyl electrophiles
* Interestingly, the reaction occurs selectively at the secondary Csp3-Br,rather than the Ar-Cl, bond.
* For each entry, a single regio- and stereoisomer (>50:1) is observed. Our current hypothesis is that a radical intermediate may be involved.
Ph
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* 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 initi
ally formed secondary alkyl radical cyclizes before reacting with nickel.
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* 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.
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* 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.
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* this catalyst system is highly selective for coupling an R-bromo amide in the presence of either an unactivated primary or secondary alkyl bromide
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* 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 enantioenrichedtrans-1,3-dimethylindane
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* Asymmetric Negishi Cross-Couplings of Secondary Allylic Chlorides
Yield:70-80%Ee:~90%
Yield:~80%Ee:70-98%
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Negishi
organozirconium reagents
Yield:70-80%Ee:~90%
Yield:~80%Ee:~90%
Yield:~80%Ee:~90%
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* 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.
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* 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,