1438
Chem. Pharm. Bull. 64, 1438–1441 (2016)
Vol. 64, No. 10
Communication to the Editor
Pd-catalyzed alkoxycarbonylation of [1,1′-binaphthalene]-2,2′-
diyl ditriflate using carbon monoxide (CO) gas.19) Proving the
utility of this pioneering work, many other researchers have
used this method to obtain various derivatives.20–23) While this
method gives dicarboxylates in good yield under relatively
mild, weakly basic conditions, use of the highly toxic CO gas
is a major drawback.
Practical Synthesis of Axially Chiral
Dicarboxylates via Pd-Catalyzed
External-CO-Free Carbonylation
Hideyuki Konishi, Fumika Hoshino, and
Kei Manabe*
To circumvent the use of toxic CO gas, alternative methods
using CO surrogates have attracted much attention in recent
years.24–27) We recently reported a series of external-CO-free
carbonylation of haloarenes utilizing phenyl formate or other
formic acid derivatives as CO surrogates.28–32) These CO sur-
rogates can generate CO under mild conditions in a closed
reaction vessel, and this CO is consumed during carbonyl-
ation in a highly safe and efficient manner. We hypothesized
that this external-CO-free carbonylation would be a power-
ful tool to directly afford not only [1,1′-binaphthalene]-2,2′-
dicarboxylates, but also other axially chiral dicarboxylates
from the corresponding ditriflates without handling toxic CO
gas or strongly basic compounds. We report herein a practical
synthetic method for various axially chiral dicarboxylates in
an enantiomerically pure form using phenyl formate as a CO
surrogate.
School of Pharmaceutical Sciences, University of Shizuoka; 52–1
Yada, Suruga-ku, Shizuoka 422–8526, Japan.
Received June 17, 2016; accepted July 18, 2016;
advance publication released online August 3, 2016
We have developed a safe and practical synthetic method for
preparing axially chiral diphenyl dicarboxylates using Pd-cat-
alyzed external-CO-free carbonylation with phenyl formate
as a CO surrogate. Optimized conditions consisted of axially
chiral [1,1ꢀ-binaphthalene]-2,2ꢀ-diyl ditriflate and its conge-
ners, each easily prepared from commercially available enan-
tiomerically pure diols, Pd(OAc)2, 1,3-bis(diphenylphosphino)-
propane, ethyldiisopropylamine, and no solvent. To demon-
strate the potential utility of these products, this method was
conducted on gram-scale and the phenyl ester products were
converted to other useful compounds, and both processes
were carried out without difficulty.
We first optimized the reaction conditions for Pd-catalyzed
phenoxycarbonylation of (R)-[1,1′-binaphthalene]-2,2′-diyl
ditriflate (1), which was easily prepared from enantiomeri-
cally pure (R)-1,1′-bi-2-naphthol,33) using phenyl formate as
Key words axially chiral dicarboxylate; carbonylation; phen-
yl formate; carbon monoxide surrogate; palladium; catalysis
Axially chiral compounds have found wide applications a CO surrogate, as shown in Table 1. Following Takaya’s
as ligands and organocatalysts in asymmetric organic reac- procedure with CO gas,19) we chose Pd(OAc)2 as a Pd source,
tions.1–5) Their chiral backbones effectively construct an asym- 1,3-bis(diphenylphosphino)propane (DPPP) as a ligand, ethyl-
metric environment around the molecules, enabling catalytic diisopropylamine as a base, and dimethyl sulfoxide (DMSO)
transformations, often with high enantioselectivity. A number as a solvent. However, only a trace amount of the desired
of biaryl and spirocyclic chiral ligands are commercially phenyl ester 2 was obtained under the external-CO-free condi-
available from multiple suppliers, and many recent papers tions (entry 1). Solvent screening (entries 2–5) yielded N,N-
mentioning the development of novel axially chiral ligands dimethylformamide (DMF) as the solvent of choice (entry
and organocatalysts indicate increasing demand and potential 5), though a certain amount of monocarbonylated by-product
of axially chiral compounds for asymmetric catalysis.
3 was still present. A review of other phosphine ligands at
In the search for highly effective chiral ligands and or- slightly raised temperatures (entries 6–11) showed that DPPP
ganocatalysts, [1,1′-binaphthalene]-2,2′-dicarboxylic acid and was the best ligand.34) Notably, subtle differences in the ligand
its derivatives such as esters are attractive axially chiral structure significantly influenced the outcome of the reaction.
compounds.6–9) However, most previous methods for the Xantphos and tri(tert-butyl)phosphine, which were effective
synthesis of the enantiomerically pure dicarboxylic acid and in the aryloxycarbonylation of haloarenes,28,29,31,32) were both
dicarboxylates required multiple tedious steps.10–17) In addi- not suitable for the reaction of 1 with phenyl formate, prob-
tion, many of the methods include time-consuming optical ably owing to steric repulsion between the substrate and the
resolution of racemic dicarboxylic acid. Therefore, it is desir- substituents of these ligands. Decreasing of the amount of
able to develop more practical synthetic methods with fewer DPPP improved the yield (entries 12, 13), probably because
steps. Since enantiomerically pure 1,1′-bi-2-naphthol is readily
available from many suppliers, it would be an efficient starting
point in the synthesis of the targeted dicarboxylates (Chart 1).
Recently, Hamashima and colleagues reported the synthesis
of dicarboxylic acid from 1,1′-bi-2-naphthol via lithiation of
[1,1′-binaphthalene]-2,2′-diyl diphosphate followed by car-
boxylation with carbon dioxide.18) While this method affords
dicarboxylic acid in high yield in two steps, the involvement
of the strongly basic dilithiated intermediate might prove
unmanageable with more complex substrates. As another
route to [1,1′-binaphthalene]-2,2′-dicarboxylates from 1,1′-bi-
2-naphthol, Takaya and colleagues previously reported the
Chart 1. [1,1′-Binaphthalene]-2,2′-dicarboxylates from 1,1′-Bi-2-naph-
thol
*To whom correspondence should be addressed. e-mail: manabe@u-shizuoka-ken.ac.jp
© 2016 The Pharmaceutical Society of Japan
Konishi, Hideyuki
