Chemistry Reference
In-Depth Information
11.3 Chiral Electrophiles
11.3.1 Stereospecific Cross-Coupling of Alkyl Electrophiles
As noted in the Introduction, primary alkyl electrophiles have been suc-
cessfully used as coupling partners in the Suzuki-Miyaura reaction for
decades.
71-73
Thus, in addition to coupling reactions of secondary boronic
esters and their derivatives as a route to the creation of stereocenters via
Suzuki-Miyaura chemistry, the use of secondary electrophiles is another
possibility.
10
Since the oxidative addition of alkyl bromides with Pd typically
proceeds via an S
N
2 manifold,
74-77
this provides a potentially valuable
method for the use of these and related electrophiles in cross-coupling
chemistry.
The first examples of secondary alkyl electrophiles used competently in C-
C bond-forming events were in the Negishi manifold of coupling reactions.
In 2003, Rovis and co-workers reported a Ni-catalyzed decarbonylative C-C
coupling of meso-anhydrides with diphenylzinc.
78
The decarbonylation of
the initially formed RCONi species was driven by the in situ formation of an
Ni-CO complex (Scheme 11.12), which, although effective, requires a super-
stoichiometric amount of Ni as the CO trap. The observation of only one
diastereomer and the lack of exo-endo inversions demonstrate the con-
figurational stability of the C-Ni bond under the specific reaction conditions
(Scheme 11.12).
In the realm of alkyl halides themselves, building on the work of Stille and
co-workers, who showed that enantiomerically enriched 2-phenethyl brom-
ide (111) undergoes stereospecific Pd-catalyzed carbonylation,
74
Carretero
and co-workers demonstrated that the same enantiomerically enriched
bromide could undergo Kumada-Corriu coupling with almost perfect ste-
reoinversion.
79
The use of Xantphos as a ligand was shown to be important
to prevent b-hydride elimination and, under optimized conditions, the re-
action proceeded with very high yield, providing another interesting method
for the synthesis of 1,1-diarylethanes [eqn (11.25)].
O
H
H
CO
2
H
Conditions
R
Conditions
O
R
O
R
R
CO
2
H
Ph
O
H
Ph
H
O
O
105
106
107,
R-R = CH= CH
108,
R-R = CH
2
CH
2
109,
R-R = CH= CH
110,
R-R = CH
2
CH
2
Conditions
= 1. Ni(COD)
2
(1.5 eq),
neocuproine (1eq), dpp b (0.5 eq), THF, 66°C, 3h
2. Ph
2
Zn (2 eq),
p-
Fstyrene (1 eq)
Scheme 11.12 Observation of net retention of configuration in Ni-mediated Negishi
coupling of anhydrides.
Search WWH ::
Custom Search