Modular synthesis of Ar-BINMOL-phos for catalytic asymmetric alkynylation of aromatic aldehydes with unexpected reversal of enantioselectivity

Article abstract of DOI:10.1002/adsc.201301128

An interesting group of multifunctional phosphines (Ar-BINMOL-Phos; Ar-BINMOL=1,1-binaphthalene-2-α-arylmethanol-2-ol) with multi-stereogenic centers of axial and sp³-central chirality has been prepared successfully from a single chiral source through a concise synthetic route, in which the neighbouring lithium-promoted [1,2]-Wittig rearrangement proceeding with excellent diastereoselectivity and enantioselectivity is the key process in this approach. Also, in the catalytic alkynylation of aromatic aldehydes with terminal alkynes, the combination of these Ar-BINMOL-Phos ligands with dimethylzinc was found to be an effective catalyst system to afford predominantly the S-configured propargylic alcohols, whereas the additional use of calcium hydride and n-butyllithium along with the same Ar-BINMOL-Phos ligands gave the R-configured products in high yields and excellent enantioselectivities (up to >99% ee).

Full text of DOI:10.1002/adsc.201301128

COMMUNICATIONS
DOI: 10.1002/adsc.201301128
Modular Synthesis of Ar-BINMOL-Phos for Catalytic
Asymmetric Alkynylation of Aromatic Aldehydes with
Unexpected Reversal of Enantioselectivity
Tao Song,a Long-Sheng Zheng,a Fei Ye,a Wen-Hui Deng,a Yun-Long Wei,a
Ke-Zhi Jiang,a and Li-Wen Xua,b,*
a
Key Laboratory of Organosilicon Chemistry and Material Technology of Ministry of Education, Hangzhou Normal
University, Hangzhou, Zhejiang 310003, Peopleꢀs Republic of China
Fax : (+86)-571-2886-5135; e-mail: liwenxu@hznu.edu.cn
Key Laboratory of Applied Surface and Colloid Chemistry, Ministry of Education (MOE) and School of Chemistry and
b
Chemical Engineering, Shaanxi Normal University, Xi’an 710062, Peopleꢀs Republic of China
E-mail: licpxulw@yahoo.com
Received: December 13, 2013; Revised: February 2, 2014; Published online: && &&, 0000
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201301128.
Abstract: An interesting group of multifunctional
phosphines (Ar-BINMOL-Phos; Ar-BINMOL=
tions is also a very interesting topic in asymmetric cat-
alysis and organic synthesis.[2] However, it is not an
easy task to obtain two enantiomers, either in (S)- or
(R)-form, to be produced using the same chiral
ligand. In this regard, where possible, it would be
highly important in asymmetric catalysis for both
enantiomers of a product to be produced using chiral
ligands with switchable stereoselectivity. As a distinc-
tive and switchable stereoselectivity in chirality trans-
fer of chiral ligands or catalysts, the phenomena of
enantioselectivity inversion have been realized widely
in many catalytic asymmetric reactions in the past de-
cades.[2]
Despite the successful application of asymmetric
catalysis to the preparation of a single enantiomer
with a certain chiral catalyst, the strategies involving
enantiodivergent catalysis that enable dual or reversi-
ble enantiocontrol still remain an unexpected and sig-
nificant challenge. Recently, on the basis of the same
chiral ligands or catalysts, great progress has been
made by several groups in this context,[3–10] for exam-
ple, reversal of enantioselectivity has been realized by
tuning the conformational flexibility of chiral catalysts
in asymmetric Michael reaction,[3] the addition of zinc
metal to an iron complex in the asymmetric hydrosily-
lation of ketones,[4] the use of different metal salt cat-
1,1’-binaphthalene-2-a-arylmethanol-2’-ol)
with
multi-stereogenic centers of axial and sp3-central
chirality has been prepared successfully from
a single chiral source through a concise synthetic
route, in which the neighbouring lithium-promoted
[1,2]-Wittig rearrangement proceeding with excel-
lent diastereoselectivity and enantioselectivity is the
key process in this approach. Also, in the catalytic
alkynylation of aromatic aldehydes with terminal
alkynes, the combination of these Ar-BINMOL-
Phos ligands with dimethylzinc was found to be an
effective catalyst system to afford predominantly
the S-configured propargylic alcohols, whereas the
additional use of calcium hydride and n-butyllithi-
um along with the same Ar-BINMOL-Phos ligands
gave the R-configured products in high yields and
excellent enantioselectivities (up to >99% ee).
Keywords: alkynylation; asymmetric catalysis;
chiral ligands; chirality inversion; phosphines
In asymmetric organometallic catalysis, chiral ligands alysts,[5] achiral counteranion-induced reversal of
generally play a critical role in numerous stereoselec- enantioselectivity in ruthenium-catalyzed hydrogena-
tive transformations. Thus the design and synthesis of tion,[6] achiral acid- or base-induced switch in the or-
efficient chiral ligands is an area of permanent inter- ganocatalytic aldol and Mannich reactions,[7] chiral
est for developing efficient enantioselective metal-cat- anion-dependent inversion in ruthenium-catalyzed hy-
alyzed reactions that provide facile access to optically drohydroxyalkylation,[8] temperature-dependent re-
pure compounds.[1] Besides, for a chiral ligand with versal of enantioselectivity in the hydroformylation of
a single absolute configuration, the phenomenon of styrene,[9] and others.[10]
chirality inversion in ligand-directed asymmetric reac-
Adv. Synth. Catal. 0000, 000, 0 – 0
ꢁ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1
ÞÞ
These are not the final page numbers!

COMMUNICATIONS
Tao Song et al.
Scheme 1. Synthesis of chiral Ar-BINMOL-Phos (5).
Here we report the enantioselective alkynylation of tion of the naphthol group with chloromethylmethyl
aldehydes by the featured Ar-BINMOL-based phos- ether (MOMCl), we then achieved the introduction
phine, in which we describe the unique effect of lithi- of diphenylphosphine to the molecule 2 that led to
um and calcium upon the absolute configuration of the formation of protected phosphine 3. Because of
the products because of switchable stereoselectivity in the low reactivity of compound 3 in the [1,2]-Wittig
this catalytic alkynylation reaction.
rearrangement,[11] it was then converted to into 4. No-
Recently, we have developed a practical methodol- tably, the intermediate was difficult to be purified by
ogy for the preparation of an interesting type of flash column chromatography because it contained
chiral diols with multi-stereogenic centers, Ar-BIN- traces of by-product 1a (<5%) with similar polarity
MOLs, in which the simple axial chiral monoalkylated (detected by TLC and GC-MS). Since the trace by-
BINOLs could be converted into optically pure 1,1’- product did not affect the next [1,2]-Wittig rearrange-
binaphthalene-2-a-arylmethanol-2’-ols
(Ar-BIN- ment, the product 4 was used directly for the next
MOLs) with axial and sp3-central chirality through an step. Subsequently, the syntheses of synthetically
asymmetric [1,2]-Wittig rearrangement.[11] In this ap- useful Ar-BINMOL-based phosphine ligands 5a–
proach, the process of axial-to-central chirality trans- c with axial and sp3 central chirality were performed
fer led to the synthesis of a broad of range of chiral smoothly through neighbouring lithium-promoted
1,1’-binaphthalene-2-a-arylmethanol-2’-ols with vari- [1,2]-Wittig rearrangements.[11] The total yields of the
ous substituted groups. Over the past years, they have desired products were quite high (Scheme 1), and the
proved to be attractive chiral ligands in several enan- enantiomeric excesses of the desired chiral Ar-
tioselective transformations.[12] On the basis of previ- BINMOL-Phos (5) were >99% ee. It is noteworthy
ous findings,[11,12] we have continued to design and that the easy modulation of the R group would be
synthesize Ar-BINMOL-based P-ligands endowed useful for the modification of such phosphine ligands
with axial and sp3-central chirality. We believe that for asymmetric catalysis.
the 3-position of the substituent on the Ar-BINMOLs
To demonstrate the value of chiral Ar-BINMOL-
may also be very important for asymmetric induction, Phos (5) in promoting asymmetric transformations,
particularly for the introduction of an additional het- we chose the alkynylation of aromatic aldehydes as
eroatom-based binding center on this type of multi- a model reaction because the alkynylation products of
stereogenic ligand.
such reactions, chiral propargylic alcohols, are impor-
Initially, we developed an efficient approach to pre- tant intermediates in the synthesis of fine chemicals,
pare Ar-BINMOL-based phosphine ligands through natural products, and therapeutic agents.[13] In the
an asymmetric [1,2]-Wittig rearrangement, which pro- past decades, much interest has been focused on the
vided versatile and optically pure P-ligands for the catalytic synthesis of chiral propargylic alcohols
asymmetric alkynylation of aromatic aldehydes. The though the organozinc reagents-promoted addition of
synthesis of the Ar-BINMOL-based phosphine li- a terminal acetylene to an aldehyde.[14] After the pio-
gands is outlined in Scheme 1. The benzyl ether of neering work by Carreira et al. on the alkynylation of
1,1’-binaphthol (BINOL) 1 could be obtained easily aldehydes with stoichiometric (+)-N-methylephe-
from benzyl bromide and BINOL. And after protec- drine, ZnACTHNUTRGNEUNG
(OTf)2, and triethylamine,[15] a number of
2
asc.wiley-vch.de
ꢁ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 0000, 000, 0 – 0
ÝÝ
These are not the final page numbers!

COMMUNICATIONS
Modular Synthesis of Ar-BINMOL-Phos
N,O-based and diol ligands have been employed as portance of the hydroxy group at the benzylic posi-
chiral catalysts or ligands in these reactions. For ex- tion on Ar-BINMOL-Phos ligands in this reaction. It
ample, the use of 1,1’-bi-2-naphthol (BINOL) and its also should be noted that the combinational use of tri-
derivatives in conjunction with TiACTHNURGTNEUNG(O-i-Pr)4 and orga- phenylphosphine and Ar-BINMOL (L1) could not
nozinc reagents to facilitate alkynylation of aldehydes promote the occurrence of alkynylation (entry 10).
has been reported by the groups of Pu and Chan in- Also surprisingly, the ligands L5 and L6 with multi-
dependently.[16,17] These conditions provided good binding centers of phosphine and Schiff base[23] result-
yield and enantioselectivity with a range of substrates. ed in excellent yields but with almost no enantioselec-
Other examples include amino alcohols, imino alco- tivity (entries 8 and 9). Thus in this alkynylation reac-
hols, hydroxyl sulfamides, hydroxy carboxamides, oxa- tion, the Ar-BINMOL-Phos (5a) was one of the most
zolidines, and miscellaneous catalysts.[18] Despite the promising phosphine ligands, whereas all the other
big number of chiral ligands described so far for this phosphine ligands tested herein resulted in poor
reaction, as yet, a phosphine catalyst or ligand has not yields or low enantioselectivities. In additional investi-
been successfully developed for the catalytic asym- gations, 5a was utilized to screen the reaction condi-
metric alkynylation of aldehydes with high enantiose- tions, such as solvents and temperature. These studies
lectivity.[19a] Only Sawamura and co-workers have demonstrated that the nature of the solvent dramati-
ever reported that a Cu(I)-phosphine complex could cally impacted on the selectivity and activity of chiral
be used as an efficient catalyst in this reaction.[19b] In ligand 5a (entries 11–15 and Supporting Information,
addition, the strong demand for perfect chirality- Table S2). The effect of temperature and commercial-
transfer of a catalyst with perfect enantioselectivity ly available Me2Zn in different solvents on the zinc/
still motivates chemists to develop good strategies or 5a-mediated alkynylation of benzaldehyde was also
catalysts in this reaction with truly perfect enantiose- investigated (entries 16–18). In summary, as shown in
lectivity for at least one substrate (>99% ee). And Table 1 and Table S1 in the Supporting Information,
our aim was also to develop an efficient Ar- the best result in terms of enantioselectivity was ob-
BINMOL-derived phosphine catalyst system with tained at À108C in Et2O (marked as Method A, 85%
multi-stereogenic centers enabling both enantiomers yield and 70% ee) while the yield was decreased
of a product to be produced with a single chiral slightly in comparison to that at higher temperature.
ligand. This would ultimately provide a facile ap-
proach to the development of controllable chirality in BINMOL-Phos (5a)-promoted nucleophilic addition
the synthesis of optically pure propargylic alcohols. of terminal alkyne 7a to benzaldehyde 6a, the next
In view of our preliminary results on the Ar-
Thus, we began our investigation by examining the logical step was to investigate the effect of various ad-
catalytic activity of various Ar-BINMOL-derived ditives for enhancement of the enantioselective induc-
phosphine ligands (Ar-BINMOL-Phos) in the alkyny- tion of 5a in this reaction. Screening of numerous ad-
lation of benzaldehyde 6a with terminal alkyne 7a. Si- ditives, for example, chiral amino acids, Lewis acids,
multaneously, we also investigated the catalytic activi- Lewis base, and organometallic reagents (Table 2 and
ty of phosphine-free Ar-BINMOL L1 and other phos- Supporting Information, Table S3), revealed that im-
phine ligands (L2–L4). As shown in Table 1, different provement of the enantioselectivity in this catalytic
Ar-BINMOL-Phos ligands were effective in this reac- asymmetric alkynylation of aldehydes was not an easy
tion, and the alkynylation of benzaldehyde 6a with task. Fortunately, we found that the use of 10 mol%
terminal alkyne 7a proceeded smoothly in good yields n-BuLi with the above reaction conditions led to
and promising enantioselectivities (entries 1–3, 68– higher enantioselectivity (74% ee) with the opposite
85% isolated yields and 63–70% ee). Interestingly, the absolute configuration of 8a (entry 2). However, the
influence of the phosphine moiety on Ar-BINMOL- yield of 8a was sacrificed with only 30% in the pres-
Phos (5) was found to be significant, because employ- ence of 10 mol% n-BuLi. More interestingly, the com-
ment of the simple Ar-BINMOL (L1) led to almost binational use of n-BuLi and CaH2 led to a superior
no reaction under similar reaction conditions level of reaction efficiency. To test the synergistic
(entry 4). The C2-axially chiral monophosphine (Ph- effect of n-BuLi and CaH2 in this reaction, we investi-
NNP, L2)[20] prepared from Ar-BINMOL was also not gated the effect of temperature and the catalytic
effective in this reaction (entry 5). It was found that amounts of n-BuLi and CaH2 on the enantioselectivi-
the sp3-central chirality of the secondary alcohol on ty (entries 4–7, see also Supporting Information,
Ar-BINMOL-Phos was also one of the most impor- Table S4 and Table S5). It should be noted that the
tant groups due to low activity of phosphine ligand mixture of ligand 5a and CaH2 was not completely
L3 (entry 6, <10% yield with this ligand).[21] Surpris- soluble in the solvent, and the addition of n-BuLi led
ingly, the Endo-Shibataꢀs BINOL-derived phosphine to the formation of a clear solution, in which a possi-
L4[22] with only C2-axial chirality exhibited poor cata- ble bimetallic complex probably arises from the intro-
lytic activity and enantioselective induction in this re- duction of lithium to a calcium alkoxide or aryloxide
action (entry 7), which supported indirectly the im- of Ar-BINMOL-Phos (5a). Although the exact struc-
Adv. Synth. Catal. 0000, 000, 0 – 0
ꢁ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
3
ÞÞ
These are not the final page numbers!

COMMUNICATIONS
Tao Song et al.
Table 1. Zinc/ligand-promoted alkynylation of benzaldehyde: Effect of ligands, temperature, and solvents on yields and
enantioselectivity (Method A).[a]
Entry
Ligand
Solvent
Temperature [oC]
Yield [%][b]
ee [%][c]
1
2
3
4
5
6
7
8
5a
5b
5c
Et2O
Et2O
Et2O
Et2O
Et2O
Et2O
Et2O
Et2O
Et2O
Et2O
THF
MeO-t-Bu
toluene
DME
DCM
Et2O
Et2O
Et2O
À10
À10
À10
À10
À10
À10
À10
À10
À10
À10
À10
À10
À10
À10
À10
0
85
75
68
trace
trace
trace
10
95
94
trace
trace
50
61
trace
10
89
40
65
70
68
63
–
–
–
3
1
0
–
L1
L2
L3
L4
L5
L6
L1+PPh3
5a
5a
5a
5a
5a
9
[d]
10
11
12
13
14
15
16
17
18
–
68
58
–
21
63
70
68[e]
5a
5a
5a
À20
À15
[a]
Reaction conditions: 0.5 mmol of aldehyde, 1.5 mmol of alkyne, 0.025 mmol of ligand, 1.5 mmol of Et2Zn (1.0 mol/L, in
toluene), 1.0 mL of solvent. DME=1,2-dimethoxyethane, DCM=dichloromethane.
Isolated yields.
The ee value was determined by HPLC with a chiral column (see Supporting Information).
The combinational use of 5 mol% of ligand L1 and 5 mol% of PPh3.
Et2Zn in hexane solution was used in this reaction.
[b]
[c]
[d]
[e]
ture of lithium-calcium complex with Ar-BINMOL- L) was used, we found that Et2O was still the optimal
Phos 5a is not clear at present, the striking feature of solvent for the reactions evaluated in this work (en-
this study was the confirmation that 20 mol% of both tries 8–14). Unexpectedly, when dimethylzinc in
n-BuLi and CaH2 led to good enantioselectivity and hexane solution (1.0 mol/L) was used in this alkynyla-
isolated yield at 08C (entry 6, 85% yield and 87% ee, tion reaction, DCM was also a suitable solvent in
denoted as Method B). These promising results pro- term of isolated yield or enantioselectivity (entry 15,
moted us to examine the effect of solvents. To our de- 81% yield and 90% ee, denoted as Method C). It is
light, when dimethylzinc in toluene solution (1.0 mol/ suggested that the bimetallic Ca/Li-based catalyst
4
asc.wiley-vch.de
ꢁ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 0000, 000, 0 – 0
ÝÝ
These are not the final page numbers!

COMMUNICATIONS
Modular Synthesis of Ar-BINMOL-Phos
Table 2. Effect of additives and solvents on yields and enantioselectivity in the zinc/5a-mediated alkynylation of benzalde-
ACHTUNGTRENNUNG
hyde.[a]
Entry
Additive
Solvent
Temperature [oC]
Yield [%][b]
ee [%][c]
1
2
3
4
LiCl
n-BuLi
CaH2
Et2O
Et2O
Et2O
Et2O
Et2O
Et2O
Et2O
CH3CN
MeOH
DCM
toluene
1,4-dioxane
DCM
THF
À10
48
30
40
68
79
85
70
43
trace
30
56
46
68
10
81
30 (S)
74 (R)
63 (S)
62 (R)
82 (R)
87 (R)
32 (R)
5 (R)
À10
À10
n-BuLi/CaH2
n-BuLi/CaH2
n-BuLi/CaH2
n-BuLi/CaH2
n-BuLi/CaH2
n-BuLi/CaH2
n-BuLi/CaH2
n-BuLi/CaH2
n-BuLi/CaH2
n-BuLi/CaH2
n-BuLi/CaH2
n-BuLi/CaH2
À10
5
0
6[d]
7[e]
8[d]
9[d]
10[d]
11[d]
12[d]
13[d]
14[d]
15[d,f]
0
0
0
0
0
0
0
0
–
41 (R)
50 (R)
74 (R)
82 (R)
49 (R)
90 (R)
0
0
DCM
[a]
Reaction conditions: 0.5 mmol of aldehyde, 1.5 mmol of alkyne, 0.025 mmol of ligand, 1.5 mmol of Et2Zn (1.0 mol/L, in
toluene), and additive (10 mol%), 1.0 mL of solvent; DMC is dimethyl carbonate.
Isolated yields.
The ee value was determined by HPLC with a chiral column.
20 mol% of n-BuLi and CaH2.
[b]
[c]
[d]
[e]
[f]
30 mol% of n-BuLi and CaH2.
Method C: dimethylzinc in n-hexane solution was used (1 mol/L) in this procedure, and other conditions were similarly
to those of Method B (entry 6).
system was sensitive to solvents because of the rela- ligands without additional sp3-central chirality result-
tively unstable conformation of a possible supermo- ed in poor yields and low enantioselectivities.
lecular complex.
After chiral Ar-BINMOL-Phos 5a was identified as
In an effort to promote the privileged inversion of a reactive and enantioselective ligand for the alkyny-
enantioselectivity in this reaction, we also compared lation of benzaldehyde, the scope of this reaction was
the catalytic activity of L3 and L4 in the presence of further examined under the optimized conditions with
n-BuLi and CaH2 (Scheme 2). Unfortunately, both P- a series of other alkynes and aromatic aldehydes. No-
tably, to clarify the interesting and unexpected rever-
Scheme 2. Phosphine L3 or L4-mediated alkynylation of benzaldehyde: The role of sp3-central chirality of Ar-BINMOL-
Phos 5a.
Adv. Synth. Catal. 0000, 000, 0 – 0
ꢁ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
5
ÞÞ
These are not the final page numbers!

COMMUNICATIONS
Tao Song et al.
Scheme 3. Synthesis of both enantiomers of propargylic alcohols via enantioselective Ar-BINMOL-Phos 5a promoted alky-
nylation of aldehydes under different conditions (Methods A, B, and C, respectively).
ACHTUNGTRENNUNG
sal of the enantioselectivity, the alkynylation reaction same chiral ligand 5a. For the results of method B,
was carried out using different methods (methods A, some representative data are provided in Scheme 3.
B, and C) related to the experimental results of Alkynes and aromatic aldehydes evaluated in this
Table 1 and Table 2 (Scheme 3). With the method A, work resulted in the formation of the corresponding
the desired (S)-alkynylation products 8a–m were ob- R-configured propargylic alcohols at high levels of
tained in good to excellent yields (68–94%) and mod- yields and enantioselectivities (up to 93% ee). For ex-
erate to good enantioselectivities (44-70% ee). As an- ample, 1-(4-methoxyphenyl)-3-phenylprop-2-yn-1-ol
ticipated, all reactions proceeded smoothly under the (8b) and 3-(4-ethylphenyl)-1-(4-methoxyphenyl)prop-
reaction conditions of method B or C to give the alk- 2-yn-1-ol (8e) were obtained with 91% ee and 93%
ACHTUNGTRENNUNGynylation products with good to excellent enantiose- ee, respectively, under the reaction conditions of
lectivities (up to >99% ee) and yields, and the ob- method B. Interestingly, the method C gave the de-
served enantioselectivity is the opposite to that of the sired products in better enantioselectivities in some
lithium-free alkynylation even in the presence of the cases than did method A or method C. Especially for
6
asc.wiley-vch.de
ꢁ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 0000, 000, 0 – 0
ÝÝ
These are not the final page numbers!

COMMUNICATIONS
Modular Synthesis of Ar-BINMOL-Phos
Although a detailed mechanistic discussion is also
difficult for the additive-free Ar-BINMOL-Phos-
mediated alkynylation of aldehydes at present, we
proposed the model A shown in Scheme 4 (method
A, without CaH2/n-BuLi), similarly to a previous
working model of 1,2-addition of organozinc reagents
to aldehydes.[25] However, the proof of the coordina-
tion based on 31P NMR spectroscopy was not success-
ful because the phosphine is very unstable under the
reaction conditions. Thus, according to the reaction
results and the ESI-MS analysis (see the Supporting
Information), a catalytic model or transition state was
proposed as model B in Scheme 4. Especially from
the ESI(+)-MS analysis (see Supporting Information,
Figure S5), it is suggested that the use of n-BuLi and
CaH2 in the alkynylation of aldehydes is likely to gen-
erate a complicated dimer or oligomer of Ar-
BINMOL-Phos-based complex with multi-metal cen-
ters derived from calcium aryloxide of two Ar-
BINMOL 5a in the presence of strong base (n-butyl-
lithium)[26] (model B, Scheme 4), in which the oxygen
of the aldehyde was binding with the zinc center of
the alkynylzinc molecule and lithium alkoxide of Ar-
BINMOL-Phos. Also, the possible aromatic interac-
Figure 1. Non-linear effects in Ar-BINMOL-Phos 5a mediat-
ed nucleophilic addition of terminal alkyne 7a to 4-methoxy-
benzaldehyde 6b under different conditions (A or B). Ex-
perimental eeprod vs. eecat with different catalytic systems
based on Ar-BINMOL-Phos 5a. Method A: no addition of
&
any additive in Et2O ( , line a). Method B: standard condi-
tions with CaH2/n-BuLi (20 mol%/20 mol%) as additive in
^
Et2O ( , line b).
the case of 1-(4-methoxyphenyl)-3-(4-propylphenyl)- tion (p–p stacking of Ar-BINMOL-Phos-based com-
prop-2-yn-1-ol (8k) or 3-(4-chlorophenyl)-1-(4-me- plex with substrate)[27] and steric effects of the Ph2P
thoxyphenyl)prop-2-yn-1-ol (8m), excellent enantiose- group could stabilize this transition state. Thus this ar-
lectivity as well as yield was achieved (>99% ee). No- rangement resulted in the Si face-attack of a zinc ace-
tably, the aromatic aldehydes bearing electron-with- tylide species to aldehyde acceptor, which provides
drawing groups led to poor enantioselectivity in this the enantioselective access to R-configured propargyl-
reaction. For example, 8n was only obtained in 56%ee ic alcohol (up to >99%ee). Although a detailed
or 66%ee under method A or method B, respectively. mechanistic investigation involving CaH2 will form
Although the alkynylation of aromatic aldehydes is part of future studies, the participation of CaH2 in the
not perfect for all the substrates, this outcome repre- formation of the bimetallic lithium/calcium-based
sents a rare example of accessing both enantiomers of complex could be responsible for the improvement of
an asymmetric transformation by using a chiral ligand conversion.
possessing a common chiral source.
At last, considering the broad applications of prop-
On the basis of the previous excellent works on argylic alcohols and allenes in organic synthesis,[13,28]
zinc-mediated alkynylation,[13–15] as well as Kaganꢀs we sought to demonstrate the utility of the chiral
non-linear stereochemical effect[24] and the electro- propargylic alcohol for the synthesis of allenylic di-
spray ionization mass spectrometry (ESI-MS) analysis phenylphosphine oxides that could be easily prepared
of the present catalyst system, we hypothesized that from the reaction of propargylic alcohols with diphe-
the different enantioselective inductions arise from nylchlorophosphine (Ph2PCl).[29] Interestingly, there is
the formation of a possible zinc-containing complex no report on the synthesis of the corresponding chiral
with one or two ligands, respectively. In the previous allenylic diphenylphosphine oxides. As shown in
report,[24] the non-linear stereochemical effect of cata- Scheme 5, the 3-phenyl-1,2-allenylic diphenylphos-
lyst enantiopurity on product enantiomeric excess has phine oxide could be prepared in good enantioselec-
been an important diagnostic tool in mechanistic stud- tivity (84% ee) from the starting material with 90%
ies of asymmetric reactions. Our results of this non- ee.
linear study, graphically depicted in Figure 1, demon-
In summary, we have successfully developed an in-
strated that the non-linear curve with a slightly posi- teresting family of multifunctional chiral phosphines
tive non-linear effect might be attributed to the multi- (Ar-BINMOL-Phos, also named as HZNU-ABP)
metal centers-involved aggregation of the Me2Zn and with multi-stereogenic centers of axial and sp3-central
Ar-BINMOL-Phos. Unfortunately, it is difficult to dis- chirality from a single chiral source (BINOL) through
tinguish the difference between the two catalytic sys- a concise synthetic route, in which the enantioselec-
tems, namely that with or that without lithium/calci- tive [1,2]-Wittig rearrangement mediated by neigh-
um.
bouring lithium is the key process in this diastereose-
Adv. Synth. Catal. 0000, 000, 0 – 0
ꢁ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
7
ÞÞ
These are not the final page numbers!

COMMUNICATIONS
Tao Song et al.
Scheme 4. Proposed transition states for the Ar-BINMOL-Phos (5a) mediated alkynylation of aromatic aldehyde with termi-
nal alkyne with or without CaH2/n-BuLi.
mechanism of corresponding reactions will be carried
out and reported in the near future.
Experimental Section
The compounds of 1a–c and 2a–c have already been report-
ed in our previous work.[11,13f]
Scheme 5. Synthesis of chiral allenylic diphenylphosphine
oxide 9 from chiral propargylic alcohol 8a.
General Procedure for the Synthesis of Ligands 5a–c
4.8 mL (12 mmol) of a 2.5M n-BuLi solution in hexanes
were dropwise added to a solution of compound 2a (4.202 g,
10 mmol) in 50 mL of THF at À408C. Then the resulting so-
lution was stirred at À408C for 1 h, and subsequently, 10 mL
a solution of PPh2Cl (2.15 mL, 12 mmol, 1.2 equiv.) in THF
were added slowly at the same temperature. The reaction
mixture was then stirred for 6 h until almost full conversion
of 2a by TLC analysis. The reaction was quenched with satu-
lective synthesis of Ar-BINMOL-Phos ligands. In the
subsequent study, we evaluated these ligands in the
catalytic alkynylation of aromatic aldehydes with ter-
minal alkynes. The combination of these Ar-
BINMOL-Phos ligands with ZnMe2 afforded predom-
inantly the S-configured propargylic alcohols, whereas
the additional use of CaH2 and n-BuLi along with the
same Ar-BINMOL-Phos ligands gave the R-config- rated aqueous NH4Cl (5 mL) and stirred vigorously for
5 min. The aqueous phase was extracted with ethyl acetate
(3ꢂ40 mL). The combined organic layers were dried over
Na2SO4, and concentrated under vacuum. The residue was
purified by flash column chromatography on silica gel [pe-
troleum ether/EtOAc, 10/1 (v/v)] to give of the compound
3a as a yellow oil; yield: 4.77 g (79%). The product 3a was
used directly for the next step.
5 mL of 12M aqueous HCl were added to a solution of
compound 3a (4.77 g, 7.9 mmol) in 30 mL of THF at room
temperature. The reaction mixture was warmed to 408C and
ured products in high yields and excellent enantiose-
lectivities (up to >99% ee). Thus it was demonstrated
that the lithium-induced unexpected reversal of enan-
tioselectivity takes place in this catalytic alkynylation.
Notably, the Ar-BINMOL-Phos with privileged multi-
chirality presented herein can access both enantio-
mers from a single chiral source by the addition of
a catalytic amount of an organolithium reagent. Fur-
ther investigation involving the application and eluci-
dation of Ar-BINMOL-Phos ligand, and the detailed stirred for another 2 h, before being diluted with water (3ꢂ
8
asc.wiley-vch.de
ꢁ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 0000, 000, 0 – 0
ÝÝ
These are not the final page numbers!

COMMUNICATIONS
Modular Synthesis of Ar-BINMOL-Phos
30 mL) and extracted with ethyl acetate (3ꢂ30 mL). The
combined organic layers were dried over Na2SO4, and con-
centrated under vacuum. The residue was purified by flash
column chromatography on silica gel [petroleum ether/
EtOAc, 10/1 to 5/1 (v/v)] to give compound 4a as a yellow
solid; yield: 3.98 g (90% total yield for two steps from 2a).
dried over Na2SO4 and concentrated under vacuum. The res-
idue was purified by flash column chromatography on silica
gel.
The product 4a was difficult to purify by flash column chro- Acknowledgements
matography because it contained traces of by-product 1a (<
5%) with similar polarity. Since the trace by-product did not
affect the next [1,2]-Wittig rearrangement, the product 4a
was used directly for the next step.
This project was supported by the National Natural Science
Founder of China (No. 21173064, 51203037, and 51303043),
Zhejiang Provincial Natural Science Foundation of China
(R14B030003), and the Program for Excellent Young Teach-
ers in Hangzhou Normal University (HNUEYT, JTAS 2011-
01-014) is appreciated. XLW thanks Prof. Y. Lu (National
University of Singapore) for his help.
To a solution of compound 4a (3.98 g, 0.71 mmol) in
30 mL of THF, 14.5 mL (17.78 mmol) of 1.23M i-BuLi solu-
tion in hexanes were added at À408C for 5 min, and the
colour of the mixture turn to that of jasper, and then the re-
action was carried out at room temperature for another 2 h.
Then the reaction was quenched with saturated aqueous
NH4Cl (10 mL) and stirred for 5 min. The aqueous phase
was extracted with ethyl acetate (3ꢂ30 mL). The combined
organic layers were dried over Na2SO4 and concentrated
under vacuum. The residue was purified by flash column
chromatography on silica gel [petroleum ether/EtOAc, 10/
1 to 5/1 (v/v)] to give Ar-BINMOL-Phos ligand 5a; yield:
3.58 g (90% yield)
References
[1] For recent reviews and books; see: a) W. Tang, X.
Zhang, Chem. Rev. 2003, 103, 3029–3069; b) Q. L.
Zhou, (Ed.), Privileged Chiral Ligands and Catalysts,
Wiley-VCH, Singapore, 2011.
[2] M. Bartꢃk, Chem. Rev. 2010, 110, 1663–1705, and refer-
ences cited therein.
General Procedure for the Zinc-Mediated
Asymmetric Addition of Aromatic Alkynes to
Aldehydes
[3] M. Q. Hua, H. F. Cui, L. Wang, J. Nie, J. A. Ma,
Angew. Chem. 2010, 122, 2832–2836; Angew. Chem.
Int. Ed. 2010, 49, 2772–2776.
[4] T. Inagaki, A. Ito, J.-I. Ito, H. Nishiyama, Angew.
Chem. 2010, 122, 9574–9577; Angew. Chem. Int. Ed.
2010, 49, 9384–9387.
[5] a) H. Maheswran, P. J. A. Joseph, K. L. Prasanth, S.
Priyadarshini, P. Satyanarayana, P. R. Likhar, M. L.
Kantam, Tetrahedron: Asymmetry 2010, 21, 2158–2166;
b) D. M. Du, S. F. Lu, T. Fang, J. Xu, J. Org. Chem.
2005, 70, 3712–3715; c) Y. Liu, D. Shang, X. Zhou, Y.
Zhu, L. Lim, X. Liu, X. Feng, Org. Lett. 2010, 12, 180–
183.
[6] Z. Y. Ding, F. Chen, J. Qin, Y. M. He, Q. H. Fan,
Angew. Chem. 2012, 124, 5804–5808; Angew. Chem.
Int. Ed. 2012, 51, 5706–5710.
A solution of Me2Zn (1.5 mL, 1.0M in toluene, 1.5 mmol,
3 equiv.) and phenylacetylene were added to the solution of
ligand 5a (14 mg, 0.025 mmol) in dry diethyl ether (1 mL) at
room temperature. The resulting mixture was stirred for 1 h
and cooled to À108C. And then the benzaldehyde was
added (0.5 mmol, 50.4 mL) to the solution. The reaction mix-
ture was stirred for another 24 h at À108C, before being
quenched with saturated aqueous NH4Cl (3 mL) and ex-
tracted with Et2O (3ꢂ10 mL). The combined organic layers
were dried over Na2SO4 and concentrated under vacuum.
The residue was purified by flash column chromatography
on silica gel.
[7] a) S. A. Moteki, J. Han, S. Arimitsu, M. Akakura, K.
Nakayama, K. Maruoka, Angew. Chem. 2012, 124,
1213–1216; Angew. Chem. Int. Ed. 2012, 51, 1187–1190;
b) D. G. Blackmond, A. Moran, M. Hughes, A. Arm-
strong, J. Am. Chem. Soc. 2010, 132, 7598–7599.
[8] E. L. McInturff, E. Yamaguchi, M. J. Krische, J. Am.
Chem. Soc. 2012, 134, 20628–20631.
General Procedure for the Lithium/Calcium-
Promoted Zinc-Mediated Asymmetric Addition of
Aromatic Alkynes to Aldehydes
A solution of n-BuLi (40 mL, 0.1 mmol) was added to the
mixture of ligand 5a (14 mg, 0.025 mmol) and CaH2 (4.2 mg,
0.1 mmol) in dry DCM (1 mL) at 08C. It should be noted
that the mixture of ligand 5a and CaH2 was not completely
soluble in the solvent, and the addition of n-BuLi led to the
formation of a clear solution. Then the resulting mixture
was stirred for 0.5 h at 08C. Subsequently, Me2Zn (1.5 mL,
1.0M in hexane, 1.5 mmol) and phenylacetylene were added
to the reaction mixture at this temperature and stirring was
continued for another 0.5 h. After the benzaldehyde was
added (0.5 mmol, 50.4 mL) in one portion, the reaction was
stirred at this temperature for 72 h until almost full conver-
sion of the aldehyde by TLC analysis. Then the reaction was
quenched with saturated aqueous NH4Cl (3 mL) and stirred
vigorously for 5 min. The aqueous phase was extracted with
DCM (3ꢂ10 mL), and the combined organic layers were
[9] C. P. Casey, S. C. Martins, M. A. Fagan, J. Am. Chem.
Soc. 2004, 126, 5585–5592.
[10] For selected recent examples, see: a) G. Chen, J. Gui, P.
Cao, J. Liao, Tetrahedron 2012, 68, 3220–3224; b) M.
Yoshimura, N. Shibata, M. Kawakami, S. Sakaguchi,
Tetrahedron 2012, 68, 3512–3518; c) H. Yu, F. Xie, Z.
Ma, Y. Liu, W. Zhang, Org. Biomol. Chem. 2012, 10,
ˇ ´
ˇ ´
5137–5142; d) T. Ivsic, J. Novak, N. Doslic, Z. Hamer-
ˇ
sak, Tetrahedron 2012, 68, 8311–8317; e) G. Chen, J.
Cui, L. Li, J. Liao, Angew. Chem. 2011, 123, 7823–7827;
Angew. Chem. Int. Ed. 2011, 50, 7681–7685; f) T.
Hirose, K. Sugawara, K. Kodama, J. Org. Chem. 2011,
˝
˝
76, 5413–5428; g) G. Szollosi, I. Busygin, B. Hermꢄn, R.
Leino, I. Bucsi, D. Y. Murzin, F. Fꢅlçp, M. Bartꢃk, ACS
Adv. Synth. Catal. 0000, 000, 0 – 0
ꢁ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
9
ÞÞ
These are not the final page numbers!

COMMUNICATIONS
Tao Song et al.
Catal. 2011, 1, 1316–1326; h) F. Peng, Z. Shao, A. S. C.
2147–2152; b) X. Li, G. Lu, W. H. Kwok, A. S. C. Chan,
J. Am. Chem. Soc. 2002, 124, 12636–12637; c) G. Lu, X.
Li, W. L. Chan, A. S. C. Chan, Chem. Commun. 2002,
172–173; d) J. Ruan, G. Lu, L. Xu, Y. Li, A. S. C. Chan,
Adv. Synth. Catal. 2008, 350, 76–84.
Chan, Tetrahedron: Asymmetry 2010, 21, 465–468; i) N.
Abermil, G. Masson, J. Zhu, Org. Lett. 2009, 11, 4648–
4651; j) F. Lutz, T. Igarashi, T. Kinoshita, M. Asahina,
K. Tsukiyama, T. Kawasaki, K. Soai, J. Am. Chem. Soc.
2008, 130, 2956–2958; k) F. Xie, D. Liu, W. Zhang, Tet-
rahedron Lett. 2008, 49, 1012–1015; l) A. M. Sarotti, I.
Fernꢄndez, R. A. Spanevello, M. ꢆ. Sierra, A. G.
Suꢄrez, Org. Lett. 2008, 10, 3389–3392; m) A. Frçland-
er, C. Moberg, Org. Lett. 2007, 9, 1371–1374; n) N. N.
Reed, T. J. Dickerson, G. E. Boldt, K. D. Janda, J. Org.
Chem. 2005, 70, 1728–1731; o) M. T. Reetz, G. Mehler,
Tetrahedron Lett. 2003, 44, 4593–4596.
[18] For selected examples, see: a) B. Zheng, S. N. Li, J. Y.
Mao, B. Wang, Q. H. Bian, S. Z. Liu, J. C. Zhong, H. C.
Guo, M. Wang, Chem. Eur. J. 2012, 18, 9208–9211;
b) B. M. Trost, A. Quintard, Angew. Chem. 2012, 124,
6808–6812; Angew. Chem. Int. Ed. 2012, 51, 6704–6708;
c) B. M. Trost, M. J. Bartlett, A. H. Weiss, A. Jacobi
von Wangelin, V. S. Chan, Chem. Eur. J. 2012, 18,
16498–16509; d) D. L. Usanov, H. Yamamoto, J. Am.
Chem. Soc. 2011, 133, 1286–1289; e) Z. Y. Li, M. Wang,
Q. H. Bian, B. Zheng, J. Y. Mao, S. N. Li, S. Z. Liu,
M. A. Wang, J. C. Zhong, H. C. Guo, Chem. Eur. J.
[11] G. Gao, F. L. Gu, J. X. Jiang, K. Jiang, C. Q. Sheng,
G. Q. Lai, L. W. Xu, Chem. Eur. J. 2011, 17, 2698–2703.
[12] a) G. Gao, X. F. Bai, H. M. Yang, J. X. Jiang, G. Q. Lai,
L. W. Xu, Eur. J. Org. Chem. 2011, 5039–5046; b) E.
Fernꢄndez-Mateos, B. Maciꢄ, D. J. Ramꢃn, M. Yus,
Eur. J. Org. Chem. 2011, 6851–6855; c) E. Fernꢄndez-
Mateos, B. Maciꢄ, M. Yus, Eur. J. Org. Chem. 2012,
3732–3736; d) E. Fernꢄndez-Mateos, B. Maciꢄ, M. Yus,
Tetrahedron: Asymmetry 2012, 23, 789–794; e) G. Gao,
X. F. Bai, F. Li, L. S. Zheng, Z. J. Zhan, G. Q. Lai, K.
Jiang, F. Li, L. W. Xu, Tetrahedron Lett. 2012, 53, 2164–
2166; f) F. Li, Z. J. Zheng, J. Y. Shang, K. Z. Jiang,
G. Q. Lai, J. X. Jiang, L. W. Xu, Chem. Asian J. 2012, 7,
2008–2013; g) L. S. Zheng, K. Z. Jiang, Y. Deng, X. F.
Bai, G. Gao, F. L. Gu, L. W. Xu, Eur. J. Org. Chem.
2013, 748–755; h) F. Li, L. Li, W. Yang, L. S. Zheng,
Z. J. Zheng, K. Jiang, Y. Lu, L. W. Xu, Tetrahedron
Lett. 2013, 54, 1584–1588.
´
2011, 17, 5782–5786; f) M. Rachwalski, S. Lesniak, P.
´
Kiełbasinski, Tetrahedron: Asymmetry 2010, 21, 2687–
2689; g) J.-i. Ito, R. Asai, H. Nishiyama, Org. Lett.
2010, 12, 3860–3862; h) J. Zhong, S. Hou, Q. Bian, M.
Yin, R. Na, B. Zheng, Z. Li, S. Liu, M. Wang, Chem.
Eur. J. 2009, 15, 3069–3071; i) L. Qiu, Q. Wang, L. Lin,
X. Liu, X. Jiang, Q. Zhao, G. Hu, R. Wang, Chirality
2009, 21, 316–323; j) C. Chen, L. Hong, Z. Q. Xu, R.
Wang, Org. Lett. 2006, 8, 2277–2280; k) B. M. Trost,
A. H. Weiss, A. J. von Wangelin, J. Am. Chem. Soc.
2006, 128, 8–9; l) C. Wolf, S. L. Liu, J. Am. Chem. Soc.
2006, 128, 10996–10997; m) R. Takita, K. Yakura, T.
Ohshima, M. Shibasaki, J. Am. Chem. Soc. 2005, 127,
13760–13761; n) Z. Xu, R. Wang, J. Xu, C.-S. Da, W.-J.
Yan, C. Chen, Angew. Chem. 2003, 115, 5925–5927;
Angew. Chem. Int. Ed. 2003, 42, 5747–5749; o) B. Jiang,
Z. Chen, W. Xiong, Chem. Commun. 2002, 1524–1525.
[19] Sawamura and co-workers have reported firstly an ex-
ample of enantioselective alkynylation of aldehydes
with promising enantioselectivity (up to 56% ee) in the
presence of a copper-phosphine complex: a) Y. Asano,
K. Hara, H. Ito, M. Sawamura, Org. Lett. 2007, 9,
3901–3904; and very recently, the same group reported
that copper(I) complexes with prolinol-based hydrox-
yamino phosphane chiral ligands catalytically promoted
the alkynylation aldehydes in alcoholic solvents in high
[13] P. J. Stang, F. Diederich, (Eds.), Modern Acetylene
Chemistry, Wiley-VCH, Weinheim, 2008.
[14] For reviews on zinc-mediated alkyne addition, see:
a) L. Pu, Tetrahedron 2003, 59, 9873–9886; b) P. G.
Cozzi, R. Hilgraf, N. Zimmermann, Eur. J. Org. Chem.
2004, 4095–4105; c) G. Lu, Y.-M. Li, X.-S. Li, A. S. C.
Chan, Coord. Chem. Rev. 2005, 249, 1736–1744;
d) B. M. Trost, A. H. Weiss, Adv. Synth. Catal. 2009,
351, 963–983.
[15] For selected references, see: a) D. E. Frantz, R. Fꢇssler,
E. M. Carreira, J. Am. Chem. Soc. 2000, 122, 1806–
1807; b) D. E. Frantz, R. Fꢇssler, C. S. Tomooka, E. M.
Carreira, Acc. Chem. Res. 2000, 33, 373–381; c) N. K.
Anand, E. M. Carreira, J. Am. Chem. Soc. 2001, 123,
9687–9688; d) D. Boyall, D. E. Frantz, E. M. Carreira,
Org. Lett. 2002, 4, 2605–2606; e) R. Fꢇssler, C. S. To-
mooka, D. E. Frantz, E. M. Carreira, Proc. Natl. Acad.
Sci. USA 2004, 101, 5843–5845.
enantioselectivities, and they found that a non-classic
3
À
sp -C H···O hydrogen bond plays an important role in
a highly directional catalyst-substrate interaction: b) T.
Ishii, R. Watanabe, T. Moriya, H. Ohmiya, S. Mori, M.
Sawamura, Chem. Eur. J. 2013, 19, 13547–13553.
[20] L. S. Zheng, L. Li, K. F. Yang, Z. J. Zheng, X. Q. Xiao,
L. W. Xu, Tetrahedron 2013, 69, 8777–8784.
[16] For selected examples and account, see: a) G. Gao, D.
Moore, R.-G. Xie, L. Pu, Org. Lett. 2002, 4, 4143–4146;
b) Z.-B. Li, L. Pu, Org. Lett. 2004, 6, 1065–1068; c) G.
Gao, R. G. Xie, L. Pu, Proc. Natl. Acad. Sci. USA 2004,
101, 5417–5420; d) Y. Yue, M. Turlington, X.-Q. Yu, L.
Pu, J. Org. Chem. 2009, 74, 8681–8689; e) M. Turling-
ton, Y. Du, S. G. Ostrum, V. Santosh, K. Wren, T. Lin,
M. Sabat, L. Pu, J. Am. Chem. Soc. 2011, 133, 11780–
11794; f) W. Qin, L. Pu, Synlett 2013, 1340–1363; g) W.
Chen, J. H. Tay, J. Ying, X. Q. Yu, L. Pu, J. Org. Chem.
2013, 78, 2256–2265.
[21] The preparation and characterization of Ar-BINMOL-
derived monophosphine ligand L3 is provided in the
Supporting Information.
[22] a) K. Endo, M. Ogawa, T. Shibata, Angew. Chem. 2010,
122, 2460–2463; Angew. Chem. Int. Ed. 2010, 49, 2410–
2413; b) K. Endo, D. Hamada, S. Yakeishi, M. Ogawa,
T. Shibata, Org. Lett. 2012, 14, 2342–2345; c) K. Endo,
D. Hamada, S. Yakeishi, T. Shibata, Angew. Chem.
2013, 125, 634–638; Angew. Chem. Int. Ed. 2013, 52,
606–610.
[23] The phosphine ligand L5 (HZNU-Phos) bearing match-
ing axial and sp3 central chirality from BINOL and
chiral amine was found to be an efficient ligand in the
[17] For selected examples, see: a) G. Lu, X. Li, Z. Zhou,
W. Chan, A. Chan, Tetrahedron: Asymmetry 2001, 12,
10
asc.wiley-vch.de
ꢁ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 0000, 000, 0 – 0
ÝÝ
These are not the final page numbers!

COMMUNICATIONS
Modular Synthesis of Ar-BINMOL-Phos
enantioselective copper-catalyzed conjugate addition of
organic zinc reagent to enones with excellent enantio-
selectivities and TON (high TON of 17600 and up to
99% ee), see: F. Ye, Z. J. Zheng, W. H. Deng, L. S.
Zheng, Y. Deng, C. G. Xia, L. W. Xu, Chem. Asian J.
2013, 8, 2242–2253.
[26] Selected example for calcium aryloxide of BINOL, see:
a) G. Kumaraswamy, M. N. V. Sastry, N. Jena, Tetrahe-
dron Lett. 2001, 42, 8515–8517; for selected review, see:
b) Y. Yamashita, T. Tsubogo, S. Kobayashi, Chem. Sci.
2012, 3, 967–975; similarly, about magnesium binaph-
tholates, see: c) M. Hatano, T. Horibe, K. Ishihara,
Angew. Chem. 2013, 125, 4647–4651; Angew. Chem. Int.
Ed. 2013, 52, 4549–4554.
[27] Recently, Krenske and Houk have summarized and re-
ported the important role of attractive non-covalent in-
teraction of aromatic rings in many catalytic enantiose-
lective transformations: E. H. Krenske, K. N. Houk,
Acc. Chem. Res. 2013, 46, 979–989.
[24] a) C. Puchot, O. Samuel, E. DuÇach, S. Zhao, C.
Agami, H. B. Kagan, J. Am. Chem. Soc. 1986, 108,
2353–2357; b) D. Guillaneux, S. H. Zhao, O. Samuel, D.
Rainford, H. B. Kagan, J. Am. Chem. Soc. 1994, 116,
9430–9439; c) C. Girard, H. B. Kagan, Angew. Chem.
1998, 110, 3088–3127; Angew. Chem. Int. Ed. 1998, 37,
2922–2959.
[25] a) K. Soai, S. Niwa, Chem. Rev. 1992, 92, 833–856;
b) M. Yamakawa, R. Noyori, J. Am. Chem. Soc. 1995,
117, 6327–6335; c) M. Yamakawa, R. Noyori, Organo-
metallics 1999, 18, 128–133; d) L. Pu, H. B. Yu, Chem.
Rev. 2001, 101, 757–824; e) R. Infante, A. Gago, J.
Nieto, C. Andrꢈs, Adv. Synth. Catal. 2012, 354, 2797–
2804.
[28] For a recent monograph, see: N. Krause, A. S. K. Ha-
shimi, Modern Allene Chemistry, Vols. 1 and 2, Wiley-
VCH, Weinheim, Germany, 2004.
[29] a) C. Santelli-Rouvier, L. Toupet, M. Santelli, J. Org.
Chem. 1997, 62, 9030–9047; b) G. He, C. L. Fu, S. M.
Ma, Tetrahedron 2009, 65, 8035–8042.
Adv. Synth. Catal. 0000, 000, 0 – 0
ꢁ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
11
ÞÞ
These are not the final page numbers!

COMMUNICATIONS
12 Modular Synthesis of Ar-BINMOL-Phos for Catalytic
Asymmetric Alkynylation of Aromatic Aldehydes with
Unexpected Reversal of Enantioselectivity
Adv. Synth. Catal. 2014, 356, 1 – 12
Tao Song, Long-Sheng Zheng, Fei Ye, Wen-Hui Deng,
Yun-Long Wei, Ke-Zhi Jiang, Li-Wen Xu*
12
asc.wiley-vch.de
ꢁ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 0000, 000, 0 – 0
ÝÝ
These are not the final page numbers!