Copper-catalyzed asymmetric alkylation of β-keto esters with xanthydrols

Article abstract of DOI:10.1002/adsc.201300627

The copper(II) triflate-tert-butyl-bisoxazoline [Cu(OTf) ₂-t-Bu-BOX]-catalyzed asymmetric alkylation of β-keto esters using free benzylic alcohols such as xanthydrols, as alkylating agents, is herein described for the first time. This green pro

Full text of DOI:10.1002/adsc.201300627

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DOI: 10.1002/adsc.201300627
Copper-Catalyzed Asymmetric Alkylation of b-Keto Esters with
Xanthydrols
Paz Trillo,a Alejandro Baeza,a,* and Carmen Nꢀjeraa,*
a
Departamento de Quꢁmica Orgꢀnica, Facultad de Ciencias, and Instituto de Sꢁntesis Orgꢀnica (ISO), Universidad de
Alicante, Apdo 99, 03080 Alicante, Spain
Fax : (+34)-96-590-3549; phone: (+34)-96-590-3549; e-mail: alex.baeza@ua.es or cnajera@ua.es
Received: July 17, 2013; Revised: September 6, 2013; Published online: && &&, 0000
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201300627.
Abstract: The copper(II) triflate-tert-butyl-bisoxa-
zoline [Cu(OTf)2-t-Bu-BOX]-catalyzed asymmetric
focused on the asymmetric a-alkylation of aldehydes
or ketones and Friedel–Crafts reactions using enam-
ine catalysis or chiral Brønsted acid-based organoca-
talysis.[5]
In the last years, we have been studying the use of
free alcohols as alkylating agents for nitrogenated and
carbon nucleophiles.[6] In this communication we ex-
plore the use of copper salts in combination with
a chiral ligand for the enantioselective alkylation of
b-keto esters, which are versatile building blocks
easily transformed into other functionalities, using
benzylic alcohols.[7,8]
ACHTUNGTRENNUNG
alkylation of b-keto esters using free benzylic alco-
hols such as xanthydrols, as alkylating agents, is
herein described for the first time. This green proto-
col renders in general the corresponding products
with good results in terms of both yields and enan-
tioselectivities using different keto esters, even
when quaternary stereocenters were created. The
scope, limitations and mechanistic aspects of the
process are also discussed.
Keywords: alcohols; asymmetric alkylation; bisoxa-
zolines; copper; b-keto esters
The reaction between xanthydrol (1a), whose deriv-
atives present pharmaceutical activity and are the
basis of different dyes and fluorescent materials,[9] and
ethyl benzoylacetate (2a) was chosen as model in
order to find the optimal conditions (Table 1). Firstly,
a preliminary screening of different privileged li-
The direct use of alcohols as alkylating reagents rep- gands,[10] such as BINAP, phosphoramidites, Jacob-
resents a straightforward, environmentally friendly sen’s Schiff base, PHOX and BOX-type paired with
and highly desirable strategy in organic synthesis CuACHTUNRGTNEUNG(OTf)2 using toluene as solvent was carried out.
since those are readily available, do not require a pre- Good enantioselectivities at low temperatures
vious manipulation or activation and generate only (À508C) were obtained only with the BOX-type li-
water as by-product.[1] In this sense, enormous prog- gands (L1–L3), the best results being those obtained
ress has been achieved in this field during the last with t-Bu-BOX (L1) (Table 1, entries 1–3).[10]
years in the use of allylic, propargylic and benzylic al- CuACHTNUTRGNEUNG(OTf)2 was not serendipitously chosen, since in our
cohols.[1] However, enantioselective alkylation pro- strategy, this salt could release TfOH which would ac-
cesses involving the use of such alcohols are still in tivate the free alcohol forming a carbocationic inter-
their infancy, probably due to the poor ability of the mediate species (see below, Figure 1), as our group,
hydroxy function as leaving group and the need for among others using other Brønsted acids, have al-
the use of a water-tolerant catalyst. Thus, allylic and ready described.[1b,6b] Additionally, we later realized
propargylic alcohols have been used as substrates in that this idea was in agreement with the mechanism
catalytic enantioselective alkylation processes em- proposal of Nishibayashiꢂs group for the asymmetric
ploying a wide variety of catalytic systems such as alkylation of b-keto phosphonates.[8] With this in
chiral metal complexes, organocatalysts or a combina- mind, we decided to explore other copper salts, such
tion of both.[2,3] On the contrary, still rare is the use of as Cu
ACTHNUGTRNE(UNG OAc)2, CuTC [copper(I) thiophene-2-carboxyl-
simple benzylic alcohols in a metal-catalyzed enantio- ate] or CuOTf·C6H6, although no reaction was ob-
selective alkylation and, since the pioneering report served. In the case of using CuOTf, low conversion
of Cozziꢂs group,[4] most of the examples reported, in- and enantioselectivity were obtained (Table 1, en-
volving these alcohols as alkylating agents, are mainly tries 4–6).
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Table 1. Optimization of the reaction conditions.[a]
Finally, two additional experiments were carried
out. The first one involving the addition 20 mol% of
Et3N, which would quench the possible TfOH acid
formed, and as observed (Table 1, entry 13) no reac-
tion at all was observed. The second experiment was
the use of 3ꢄ MS, which would remove part of the
stoichiometric amount of water formed during the re-
action and, in this case, the same enantioselectivity
but slightly lower conversion was observed (Table 1,
entry 14). It is also worth mentioning that small
changes in the concentration do not seem to play
a crucial role since similar results were obtained when
the alcohol concentration changed from 0.1M to
0.15M. However, lowering concentration to 0.05M
caused a considerable drop to 43% in the enantiose-
lectivity of 3aa.
Solvent Conv. [%][b] ee [%][c]
Once the optimal reaction conditions were estab-
lished, i.e., the use of 1.4 equiv. of keto ester and
10 mol% of CuACHTNUTRGNE(NUG OTf)2 paired with L1 (12 mol%) as
Entry
L
CuX
1
2
3
4
5
6
7
L1 Cu(OTf)2
G
PhMe
PhMe
PhMe
PhMe
PhMe
>95
78
25
–
–
40
70
37
13
–
L2 Cu
L3 Cu
L1 Cu
N
catalytic system, in toluene at À508C, the scope of
the reaction was next evaluated. Firstly, different b-
keto esters were tested employing xanthydrol (1a)
and thioxanthydrol (1b) as substrates (Table 2). As al-
ready mentioned ethyl benzoylacetate (2a) reacted
with xanthydrol (1a) to afford adduct 3aa in good
yields and enantioselectivities at À508C (Table 2,
entry 1). At this temperature, thioxanthydrol turned
out to be unreactive. However, at 08C, good yields
and high enantioselectivities were achieved for 3ba
(Table 2, entry 2). It is worth mentioning that perfect
enantioselectivity (>99% ee) can be obtained in this
case by simple crystallization in hexanes. When the
phenyl group was replaced by a naphthyl one within
the b-keto ester, a drastic drop in the enantioselectivi-
ty was observed even at À788C (Table 2, entry 3). Ali-
phatic b-keto esters, such as 2c, 2d and 2e gave rise to
the corresponding alkylation products as racemic mix-
tures when xanthydrol was the substrate employed
despite the several sets of reaction conditions evaluat-
ed (Table 2, entries 4, 6 and 7). The same happened
with 2e reacting with thioxanthydrol (Table 2,
entry 8). In contrast, good yield and enantioselectivity
was obtained with keto ester 2c at À208C (Table 2,
entry 5). The reason behind this different behaviour
L1 CuTC
–
L1 Cu
L1 Cu
N
22
55
0
16
80
63
12
–
CH2Cl2 >95
8
9
L1 Cu
L1 Cu
L1 Cu
N
THF
Et2O
>95
>95
10
11
12
13
14
PhMe
PhMe
PhMe
PhMe
PhMe
>95[d]
70[d,e]
40[d,f]
<10[g]
80[h]
L1 Cu
L1 Cu
L1 Cu
L1 Cu
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
G
80
[a]
Unless otherwise specified, the reaction conditions were:
1a (0.15 mmol), 2a (0.30 mmol, 2 equiv.), Cu(OTf)2
AHCTUNGTRENNUNG
(10 mol%) and ligand (12 mol%) in 1.5 mL of PhMe at
À508C.
[b]
[c]
1
Determined by H NMR of the crudes.
Determined by HPLC using a chiral column Daicel Chir-
alpak IA (see the Supporting Information for details).
1.4 equiv. of 2a were employed.
[d]
[e]
[f]
The reaction was carried out at À788C.
5 mol% of CuACHTUNGTRENNUNG(OTf)2 and 7 mol% of L1 were employed.
[g]
[h]
20 mol% of Et3N were added.
3ꢄ MS (25 mg/0.15 mmol) were added.
Next, other solvents (CH2Cl2, THF and Et2O) were could be ascribed to the slower reaction rate in the
evaluated but lower enantioselectivities were thioxanthydrol case, which would favour the enantio-
achieved in comparison with PhMe (Table 1, en- discrimination step. Next, a-methyl-b-keto ester 2f
tries 7–9). Reducing the amount of keto ester (from was evaluated but only moderate yields and low enan-
2 equiv. to 1.4 equiv.) enhanced the enantioselectivity tioselectivities were obtained when xanthydrol was
of 3aa up to 80% ee (Table 1, entry 10), probably due the substrate and the reaction performed at 258C
to the partial suppression of the background TfOH- (Table 2, entry 9).
catalyzed racemic reaction. Attempts to further in-
Cyclic b-keto esters were next tested. The cyclopen-
crease this result by lowering the temperature or cata- tane derivative 2g gave rise to the corresponding ad-
lyst amount in order to slow down the reaction rate ducts 3ag and 3bg with a 73% and 90% ee, respective-
and hence favouring enantiodiscrimination, caused ly, although in this latter case low yields were
the opposite effects (Table 1, entries 11 and 12, re- achieved (Table 2, entries 10 and 11). The yield of 3bg
spectively).
can be increased by rising the temperature up to
2
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Copper-Catalyzed Asymmetric Alkylation of b-Keto Esters with Xanthydrols
Table 2. Asymmetric alkylation of xanthydrols with b-keto esters.[a]
Entry
1
2
Temp. [8C]
3
Yield [%][b]
ee [%][c]
1
2
1a
1b
À50
3aa
3ba
82
80
0
74 (45)[d]
90 (>99)[d]
3
1a
À78
3ab
83[e]
25
4
5
1a
1b
À50
À20
3ac
3bc
91[e]
rac.
81 (75)[d]
68 (69)[d]
6
1a
À50
3ad
75[e]
rac.
7
8
1a
1b
À50
À20
3ae
3be
90[e]
52[e]
rac.
rac.
9
1a
25
3af
42
43
10
11
12
1a
1b
1b
À50
À50
À20
3ag
3bg
3bg
87
37
81
73
90
70
13
14
1a
1b
À50
3ah
3bh
90[e]
42
16
34
0
15
16
1a
1b
À50
3ai
3bi
89
71
82
63
0
17
1a
À20
3aj
85
79
18
19
20
1a
1a
1b
À78
À78
0
3ak
3ak
3bk
93
87
38
42
56[f]
71
[a]
Unless otherwise stated, the reaction conditions were as follows: 1a (0.15 mmol), 2a (0.21 mmol, 1.4 equiv.), Cu
(10 mol%) and (R,R)-L1(12 mol%) in PhMe (1.5 mL).
Isolated yield after preparative TLC.
Determined by HPLC using chiral columns Daicel Chiralpak IA or Daicel Chiralcel OD-H (see the Supporting Informa-
tion for details) from the crude compounds.
In brackets yield and ee after crystallization in hexanes
Isolated yields after flash chromatography.
5 mol% of CuACHTUNGTRENNUNG(OTf)2 and 7 mol% of (R,R)-L1 were employed.
ACHTUNGTRENNUNG(OTf)2
AHCTUNGTRENNUNG
[b]
[c]
[d]
[e]
[f]
À208C with an enantioselection detriment (Table 2, tained in both cases regardless of the temperature
entry 12). In contrast, when six-membered b-keto employed (Table 2, entries 13 and 14). The benzo-con-
ester 2h was used, low enantioselectivities were ob- densed analogues 2i and 2j gave rise to the corre-
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sponding products with good enantioselectivities, es-
pecially in the case of using xanthydrol (1a) as sub-
strate, reaching 82% ee and 79% ee for 3ai and 3aj,
respectively (Table 2, entries 15–17). Finally, butyro-
lactone 2k turned out to be very reactive and in the
reaction with xanthydrol a high yield even at À788C,
although with modest enantioselectivity, was obtained
for product 3ak (Table 2, entry 18). This enantioen-
richement was increased up to 56% ee by using half
of the catalyst loading (Table 2, entry 19). The same
lactone produced the corresponding adduct 3bk with
modest yield although with 71% ee when thioxanthy-
drol was used as alkylating agent at 08C (Table 2,
entry 20). It is important to note that a slight racemi-
zation was observed after the work-up was per-
formed. However, this racemization was not detected
while the reaction took place. This fact was confirmed
when aliquots from the reaction were directly ana-
lyzed by HPLC without aqueous work-up.[10]
Scheme 2. Asymmetric alkylation of b-keto esters with benz-
hydrols.
Other nucleophiles which are prone to be alkylated (Scheme 2). The reaction of alcohols 1c, 1d and 1f
using these alcohols were also evaluated. In this failed completely, and no product was observed de-
regard, glycine imino esters and b-cyanoacetates spite several sets of conditions tested.[12] In contrast,
failed completely and with b-nitroacetates low conver- benzhydrol 1e reacted with keto ester 2a affording
sions and enantioselectivities at the best were ob- the corresponding adduct 3ea in good yield albeit
tained.[11] Unsymmetrical 1,3-diketones (4a and 4b) with low enantioselection as the best results at 08C
were also tested, and when xanthydrol was used the (Scheme 2). When the b-keto esters 2g and 2k were
corresponding adducts were isolated with high yields tested under several sets of conditions the reaction
but as racemic mixtures. However, when benzoylace- worked but the alkylation products were isolated as
tone (4a) was allowed to react with the less reactive racemic mixtures.
thioxanthydrol (1b) the alkylation product 5ba with
Finally, and since presumably a carbocation is
low yield and high 85% ee was obtained. Rising the formed in the reaction media, the same b-keto esters
temperature up to À208C produced a considerable 2a, 2g and 2k were allowed to react with tropylium
drop in the optical purity. Encouraged by this result tetrafluoroborate (1g) (Scheme 3). In all the cases,
the cyclic derivative 4b was tested but unfortunately good yields were achieved for the corresponding ad-
gave rise to the corresponding product 5bb as a race- ducts at 08C, but only a low enantioselection (30%
mic mixture regardless the temperature employed ee) was achieved when benzoylacetate (2a) was em-
(Scheme 1).
ployed. It is important to note that it was necessary to
Next, different benzylic alcohols, which would gen- add a small amount of water in order to facilitate the
erate a rather stable carbocation were evaluated as al- tropylium saltꢂs solubility, otherwise low yields were
kylating agents. Thus, benzhydrols 1c–1e, and triphe- obtained.
nylmethanol (1f) were taken into account and were
Concerning the reaction mechanism, the facts that
allowed to react with b-keto esters 2a, 2g and 2k the reaction failed completely when Et3N (20 mol%)
and the yield decreased when 3ꢄ MS were added
(Table 1, entries 13 and 14, respectively), revealed the
importance of the TfOH and H2O formed in the reac-
tion media. The acid, as mentioned above, would be
Scheme 1. Asymmetric alkylation of unsymmetrical 1,3-dike-
tones.
Scheme 3. Asymmetric alkylation with tropylium salt 1g.
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Copper-Catalyzed Asymmetric Alkylation of b-Keto Esters with Xanthydrols
released from the copper salt after the coordination
Finally, we wondered why xanthydrols, among sev-
of b-keto ester through the corresponding enolate and eral benzylic alcohols tested, perform better for the
then would activate the benzylic alcohol, eventually enantioselective alkylation of b-keto esters. A possi-
giving rise to the carbocation which, in principle, ble explanation could be due to the fact that cations
would react in an enantiospecific manner with the derived from xanthydrols are aromatic and planar,
enolate. However, and since, as reported by us,[6b] therefore they can accommodate more easily to the
TfOH is able to catalyze the racemic alkylation by chiral environment. In contrast, benzhydrols 1c–1f are
itself (background reaction) and due to the reversibil- more sterically crowded (especially in the case of 1f),
ity of the reaction,[13] a possible copper-catalyzed reso- and the corresponding cations (with the exception of
lution of the racemic product could be not discarded. 1e) are equally or more reactive than the xanthylium
In this sense, racemic 3aa together with and a stoichio- one,[15,16] hence only allowing the reaction with small
metric amount of H2O were stirred in toluene at molecules such as water. In the case of tropylium ion
À508C for 20 h in the presence of L1-Cu
ACHTUNGRTEN(NUNG OTf)2 1g which is also planar and aromatic, the problem
(10 mol%). After this time no enantioenrichment was could be the low reactivity of this specie (E=
observed, discarding the chiral resolution and point- À3.49),[15,16] as in the case of the cation derived from
ing towards the possible mechanism depicted in 1e (E=À7.02)[15,16] allowing the background racemic
Figure 1, which resembles that proposed by Nishi- reaction.
bayashi et al.[8] Thus, as already mentioned, the
It is important to note that despite several trials the
copper-enolate would react with the in situ formed absolute configurations of these new synthesized
carbocation, TfOH-catalyzed in a SN1-type reaction, products were not determined. Efforts to determine
to produce the desired optically active product.
the absolute configuration and to gain more informa-
The role of water in the reaction media is not clear tion about the reaction mechanism and the particular
at this point. We speculate that the stoichiometric reactivity of xanthydrols by a combination of experi-
amount of water formed could facilitate the solubility mental and computational methods are currently
of the ionic pair formed, explaining the lower yields being carried out in our group. Nevertheless, the com-
obtained in its absence (Table 1, entry 14). In addi- parison between the optical rotation sign of product
tion, H2O could be involved in the catalytic cycle, 3ai and a recently published similar compound, points
since the presence of water would generate an aquo- towards (R)-configured alkylated b-keto ester prod-
copper(II)-L1 complex (and not forming the original ucts.[17,18]
complex anymore), as Evans et al. had already report-
In summary, we have demonstrated for the first
time that Cu(OTf)2 paired with t-Bu-BOX (L1)
ed, hence tuning the catalyst activity.[14]
AHCTUNGTRENNUNG
Figure 1. Proposed reaction mechanism.
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References
turned out to be a good catalytic system to accom-
plish the asymmetric alkylation of b-keto esters em-
ploying benzylic alcohols such as xanthydrols as alky-
lating agents. This green process, which generates
only water as by-product, was applied to a wide varie-
ty of keto esters and in most of the cases good yields
and enantioselectivities were achieved even when
chiral quaternary centers were formed. Moreover,
from the obtained results it can be concluded that
normally thioxanthydrol gave rise to higher enantio-
selectivities, although it seems to be less reactive. Fi-
nally, the reaction mechanism points towards a SN1-
type reaction between the copper(II) enantiospecifi-
cally activated b-keto ester and the in situ formed car-
bocation by means of the triflic acid.
[1] For reviews about the use of free alcohols in substitu-
tion reactions, see: a) J. Muzart, Eur. J. Org. Chem.
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[2] For recent reviews about the use of free allylic alcohols
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[3] For recent reviews about the use of free propargylic al-
cohols in catalytic asymmetric processes, see: a) Y.
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[4] P. G. Cozzi, F. Benfatti, L. Zoli, Angew. Chem. 2009,
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Experimental Section
General Procedure for the Asymmetric Alkylation of
b-Keto Esters with Alcohols
Into an evacuated, oven-dried and septum-capped flask con-
taining t-Bu-BOX ligand (L1, 5.4 mg, 0.018 mmol, 12 mol%)
and CuACHTUNGTRENNUNG(OTf)2 (5.4 mg, 0.015 mmol, 10 mol%) under an
argon atmosphere, toluene (0.5 mL) was added. The com-
plex was stirred at 258C for 90 min. After this time, the
flask was placed in a cooling bath at the corresponding tem-
perature and stirred for 10 min. Then, b-keto ester
(0.21 mmol, 1.4 equiv.) was added and the mixtxure stirred
for an additional 10 min. Next, a solution of the correspond-
ing alcohol (0.15 mmol) in toluene (1 mL, NB: prepared by
stirring the corresponding alcohol at 308C to ensure com-
plete solution) was finally added and the reaction mixture
stirred for 20 h. After this time, saturated NH4Cl (3 mL) was
added and the mixture extracted with ethyl acetate (3ꢅ
5 mL). The organic phases were dried (MgSO4) and evapo-
rated. The crudes were purified by preparative TLC or by
precipitation in hexanes to afford the chiral alkylation ad-
ducts
NB: Slight racemization was observed in some cases after
work-up and/or preparative TLC purification, which was
more pronounced when flash chromatography was carried
out. In addition, the chiral adducts must be kept in the
freezer (À208C) to avoid racemization (see ref.[13]).
[7] For a very recent work on copper-catalyzed enantiose-
lective alkylation of b-keto esters with in situ prepared
benzylic and allylic iodides from the corresponding al-
cohols, see: a) Q.-H. Deng, H. Wadepohl, L. H. Gade,
J. Am. Chem. Soc. 2012, 134, 2946. For asymmetric al-
kylation of keto esters using free propargylic alcohols
catalyzed by copper and ruthenium, see: b) M. Ikeda,
Y. Miyake, Y. Nishibayashi, Chem. Eur. J. 2012, 18,
3321.
[8] At the early stages of this research, Nishibayashiꢂs
group reported the use of a copper(II) chiral complex
for the asymmetric alkylation of b-keto phosphonates
using benzylic alcohols: M. Shibata, M. Ikeda, K. Mo-
toyama, Y. Miyake, Y. Nishibayashi, Chem. Commun.
2012, 48, 9528.
Acknowledgements
Spanish Ministerio de Ciencia e Innovaciꢀn (MICINN)
(projects CTQ2010-20387 and Consolider Ingenio 2010,
CSD2007-00006), FEDER, the Generalitat Valenciana
(PROMETEO 2009/039) and the University of Alicante are
gratefully acknowledged for financial support. A. B. would
also like to thank MICINN for a Juan de la Cierva contract
(JCI-2009-03710) and the University of Alicante (Project
GRE12-03).
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Copper-Catalyzed Asymmetric Alkylation of b-Keto Esters with Xanthydrols
[9] For the use of 9-xanthenyl-acetic and -glycolic acids as
antispasmodic agents, see: a) A. A. Goldberg, A. H.
Wragg, J. Chem. Soc. 1957, 4823. For the use of xan-
thene derivatives in dyes and as organic fluorescent la-
belling molecules, see: b) M. Sameiro, T. GonÅalves,
Chem. Rev. 2009, 109, 190.
[15] The E values (electrophilicity parameters in Mayrꢂs
scale) are related with carbocation stability and hence
with the reactivity. Thus, lower E value implies higher
stability and lower reactivity.
E E
(1a+)= +0.47;
(1c+)= +5.47; E (1d+)=0; E (1f+)= +0.51. Extracted
from: a) S. Minegishi, H. Mayr, J. Am. Chem. Soc.
2003, 125, 286; b) J. Ammer, C. Nolte, H. Mayr, J. Am.
Chem. Soc. 2012, 134, 13902.
[10] See the Supporting Information for further experi-
ments.
[11] Ethyl nitroacetate reacting with xanthydrol (1a) pro-
duced the corresponding alkylation product with low
yields and enantioselectivities at À208C. Raising the
temperature implies better yields but racemic mixtures.
[12] The same behaviour was observed by Cozzi et al. in the
asymmetric a-alkylation of aldehydes (see ref.[4]).
[13] We hypothesized the reversibility of the reaction based
on the observed racemization of the crude compounds
when were left to stand at room temperature (within
days) or in a fridge (within weeks). This racemization
was observed even with quaternary chiral centers and
was more pronounced with tertiary stereocenters.
[14] The group of Evans has isolated the Cu(II)-BOX aquo-
complex depicted below and elucidated its crystal
structure when small amounts of water were present in
the reaction media. See: a) D. A. Evans, E. J. Olhava,
[16] For reviews about electrophilicity and reactivity of sta-
bilized carbocations, for example, see: a) H. Mayr,
A. R. Ofial, Pure Appl. Chem. 2005, 77, 1807; b) H.
Mayr, A. R. Ofial, J. Phys. Org. Chem. 2008, 21, 584;
c) P. G. Cozzi, F. Benfatti, Angew. Chem. 2010, 122,
264; Angew. Chem. Int. Ed. 2010, 49, 256.
[17] During the submission of this manuscript we became
aware of a very recent publication dealing with a cata-
lytic asymmetric cross-dehydrogenative coupling be-
tween b-keto esters and xanthene derivatives using
a chiral bimetallic [Fe(II) and Ni(II)] catalytic system:
W. Cao, X. Liu, R. Peng, P. He, X. Feng, Chem.
Commun. 2013, 49, 3470.
[18] The optical rotation value of 3ai is [a]2D0: À116.6 (c 1,
CHCl3, 82% ee, see the Supporting Information for
more details), in comparison with the value of the
below depicted product the configuration of which was
uniquivocally assigned by X-ray analysis (see ref.[17]).
J. S. Johnson, J. M. Janey, Angew. Chem. 1998, 110,
3553; Angew. Chem. Int. Ed. 1998, 37, 3372. For
a review from the group about Cu(II)-BOX complexes
in asymmetric catalysis, see: b) J. S. Johnson, D. A.
Evans, Acc. Chem. Res. 2000, 33, 325.
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COMMUNICATIONS
8 Copper-Catalyzed Asymmetric Alkylation of b-Keto Esters
with Xanthydrols
Adv. Synth. Catal. 2013, 355, 1 – 8
Paz Trillo, Alejandro Baeza,* Carmen Nꢀjera*
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These are not the final page numbers!