Transcript BINOL

Enantioselective Synthesis of
Biphenols from 1,4-Diketones by
Traceless Central-to-axial Chirality
Exchange
Research By:
F Guo, LC Konokol, and RJ Thomson; Northwestern University
Summary by:
Sonja Gamby; UMCP
Some terms
“Axial Chirality”
Axial chirality results from a hindered axis of rotation as
opposed to a chiral center
“Traceless”
Denotes transition from sp3 to sp2 and the exchange
between typical “central” chirality and axial chirality
Common molecule exhibiting axial
chirality - BINOL
• The original synthesis of BINOL was reported by
Pummerer et al. in 1926.
• Original syntheses involved oxidative coupling of the
two naphthol units induced by FeCl3.
• There are two methods for the preparation of chiral
binaphthol ligands: (a) through coupling reactions
of substituted naphthol units and (b) through
regioselective modification of the binaphthol
scaffold.
Derivatives of BINOL: Why and
How?
• Subject to racemization in acidic or basic media
• Limited control over electronics and sterics of metal
center
• Useful in a variety of transformations
Electrophilic aromatic substitutions in conjunction with
protection of the hydroxyl moieties are a quick route to a
vast library of derivatives
…Some derivatives
Kelly et al.
Diels-Alder reactions of naphthoquinone derivatives
O
I.
O
O
B
O
Kobayashi et al.
Mannich Reaction
involving silyl enolates
II.
O
Ph
Ph
HO
OH
Ph
Ph
BINAP for use in asymmetric
catalysis
… To discover high-performance asymmetric catalysts,
developing an excellent chiral ligand is crucial. Attracted by its
molecular beauty [Chemica Scripta 1985, 25, 83], we initiated
the synthesis of BINAP (2,2’-bis(diphenylphosphino)-1,1’binaphthyl) [J. Am. Chem. Soc. 1980, 102, 1932] in 1974 at
Nagoya with the help of H. Takaya, my respected long-term
collaborator. BINAP was a new fully aromatic, axially
dissymmetric C2 chiral diphosphine that would exert strong
steric and electronic influences on transition metal complexes.
Its properties could be fine-tuned by substitutions on the
aromatic rings. …
Ryoji Noyori, Nobel Lecture, December 8, 2001
2,2'-bis(diphenylphosphino)-1,1'binaphthyl
• Synthesis from BINOL
Asymmetric Hydrogenation (Noyori et al.)
..to reduce B-keto esters
…in the Isomerization of allylic amines
Limited routes to axially chiral biphenyls
I.Direct asymmetric Coupling
Fusion of two naphthol rings using transition
metals
OH
Cu, Va, Zr..
HO
OH
OH
II. Atropselective transformation of preformed
biaryls
Is there a better way??.... Yes!
Spectroscopic Confirmation
Scope of Methodology
O
O
+ ArZnCl
MeO
OMe
O
a
b
MeO
Ar
OMe
MeO
O
H
OMe
H
OMe
Ar Ar
OMe
a= 1. [RhCl(((R) - BINAP)]2 2.TMSCl (3 equiv.), THF, -10 C
b = LDA, then; CuCl2 / THF
c = BF3 OEt2 / PhMe / 110 C
OH Ar
c
MeO
Ar
HO
OMe
Some Natural Products
OMe
O
O
OAc
MeO
O
MeO
O
MeO
MeO
OMe
NHAc
CO2Me
(-)allocolchicine
(-)steganacin
Acknowledgements
• Dr. Davis
• Ben Roembke