Song jin July 10, 2010 Gong Group Meeting. Palladium- and Nickel-Catalyzed Coupling Reactions ＊...

Song jinJuly 10, 2010

Gong Group Meeting

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.

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.

＊ Slow oxidative addition of alkyl halides/triflates to palladium ＊ Facile β-hydride elimination

Palladium- and Nickel-Catalyzed Coupling Reactions

＊ Pd catalyzed cross-couplings of alkyl electrophiles

＊ 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

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

J. AM. CHEM. SOC. 2003, 125, 12527

Angew. Chem. Int. Ed. 2003, 42, 5079

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

＊

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.

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

＊ 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

＊ 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.

＊ 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.

＊ 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.

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

＊ 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

＊ Asymmetric Negishi Cross-Couplings of Secondary Allylic Chlorides

Yield:70-80%Ee:~90%

Yield:~80%Ee:70-98%

Negishi

organozirconium reagents

Yield:70-80%Ee:~90%

Yield:~80%Ee:~90%

Yield:~80%Ee:~90%

＊ 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.

＊ 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,