Tri(o-tolyl)phosphine for highly efficient Suzuki coupling of propargylic carbonates with boronic acids

Article abstract of DOI:10.1039/C8CC04186E

A highly efficient catalytic system consisting of Pd₂(dba)₃·CHCl₃ and tri(o-tolyl)phosphine has been identified for the coupling of propargylic carbonates with different types of organo boronic acids at room temperature. Excellent central-to-axial chirality transfer was also demonstrated.

Full text of DOI:10.1039/C8CC04186E

View Article Online
View Journal
ChemComm
Accepted Manuscript
This article can be cited before page numbers have been issued, to do this please use: X. Zhe, H. Luo, S.
Huang, H. Qian and S. Ma, Chem. Commun., 2018, DOI: 10.1039/C8CC04186E.
This is an Accepted Manuscript, which has been through the
Volume 52 Number
1 4 January 2016 Pages 1–216
Royal Society of Chemistry peer review process and has been
accepted for publication.
ChemComm
Accepted Manuscripts are published online shortly after
Chemical Communications
www.rsc.org/chemcomm
acceptance, before technical editing, formatting and proof reading.
Using this free service, authors can make their results available
to the community, in citable form, before we publish the edited
article. We will replace this Accepted Manuscript with the edited
and formatted Advance Article as soon as it is available.
You can find more information about Accepted Manuscripts in the
author guidelines.
Please note that technical editing may introduce minor changes
to the text and/or graphics, which may alter content. The journal’s
standard Terms & Conditions and the ethical guidelines, outlined
in our author and reviewer resource centre, still apply. In no
event shall the Royal Society of Chemistry be held responsible
for any errors or omissions in this Accepted Manuscript or any
consequences arising from the use of any information it contains.
ISSN 1359-7345
COMMUNICATION
Marilyn M. Olmstead, Alan L. Balch, Josep M. Poblet, Luis Echegoyenet al.
Reactivity differences of Sc3N@C2n (2n 68 and 80). Synthesis of the
first methanofullerene derivatives of Sc N@D5h-C80
=
3
rsc.li/chemcomm

Please do not adjust margins
ChemComm
Page 1 of 5
View Article Online
DOI: 10.1039/C8CC04186E
Journal Name
COMMUNICATION
Tri(o-tolyl)phosphine for Highly Efficient Suzuki Coupling of
Propargylic Carbonates with Boronic Acids
Junzhe Xiao,a Hongwen Luo,b Shan Huang,b Hui Qian,*b and Shengming Ma*,a,b
Received 00th January 20xx,
Accepted 00th January 20xx
DOI: 10.1039/x0xx00000x
www.rsc.org/
(a) Pd-catalyzed coupling of propargylic compounds with organoboronic reagents
A highly efficient catalytic system consisting of Pd2(dba)3·CHCl3
and tri(o-tolyl)phosphine has been identifed for the coupling of
propargylic carbonates with different types of organo boronic
acids at room temperature. Excellent central-to-axial chirality
transfer was also demonstrated.
OLG
R3
R2
R1
R4
R2
R3
•
R1
O
cat. [Pd]
R4BX2
+
R3
OH
R1
R4
R4 = aryl or alkenyl
Due to the importance and increasing interest of allenes,1,2
chemists have been focusing on developing efficient methods
for the synthesis of different types of allenes.3 One of the most
straightforward methods would be the palladium-catalyzed
coupling of propargylic derivatives with organometallic
reagents.4 Although the commercially available organoboronic
compounds have also been applied to couple with propargylic
compounds (Scheme 1a),5 however, there still remain some
challenges such as limitation for rather sluggish alkyl boronic
compounds (Scheme 1b),5a efficiency for chirality transfer,5f,5g,5i
and high temperature (mostly above 60 oC). Regiocontrol is
another issue in such reactions since such coupling at γ or α
position would give allenes5a,5d-i or alkynes6 and in some cases,
the allene-alkyne mixture.5b,c Here we wish to report a highly
active catalytic system with a commercially available robust
ligand for such coupling reactions at room temperature
covering a very broad scope affording allenes efficiently
(Scheme 1c).
•
R2
R2
R3
R1
(b) The only example with alkyl boronic compound with Pd catalysis
cat. Pd(dppf)Cl2
K3PO4
OCO2Me
n-Bu
n-Hex
n-Hex
Me
+ n-Hex-9-BBN
•
THF, reflux
n-Hex
Me
n-Bu
69% yield
(c) This work:
OCO2Me
R3
cat. Pd2(dba)3•CHCl
cat. tri(o-tolyl)phosphine
3
R1
R4
R3
R2
+ R4B(OH)2
•
R2
2.0 equiv H2O
dioxane, rt
R1
up to 96% yield
√
√
√
√
√
Mild conditions
Broad substrate scope
High to excellent yields
Excellent selectivity
Excellent chirality transfer
Scheme 1. Pd-catalyzed coupling of propargylic compounds with organoboronic
reagents
We began the study with propargylic carbonate 1a and
phenylboronic acid 2a as the model substrates to identify the
ligands for the reaction at ambient temperature, thus, the
phenyl)phosphine (L5) failed to further improve the yield.
Interestingly, we found that bis(ortho-methoxy)phenyl phenyl
phosphine (L6) could give 3aa in 41% yield. Excitingly, tri(o-
o
temperature for the coupling reaction was set at 30 C. o-
(Diphenylphosphino)benzaldehyde (L1) was initially employed
as the ligand5i and the desired allene product 3aa was formed
in only 58 % yield. Triphenylphosphine (L2) resulted in 3% yield
of 3aa with 97% recovery of 1a. Tuning the electronic property
of the phenyl group by using para-methyl-substituted triphenyl
phosphine (L4) improved the yield to 38%. Tris(4-methoxy)-
tolyl)phosphine (L7) provided 83% yield of 3aa with only 4%
recovery of 1a. Zheda-Phos (L8)
product.
7
failed to give the allene
Other palladium catalysts did not improve the yield (Table
2, entries 1-4). No better result was obtained in MTBE,
toluene, THF, Et2O, or MeCN (Table 2, entries 5-9). The yield
could be slightly improved to 87% with a higher loading of
palladium catalyst and the ligand (Table 2, entry 10). To our
surprise, the addition of 2 equiv of water further accelerated
the coupling reaction, which completed in 30 min with almost
quantitative yield even at room temperature (Table 2, entry
11).
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 1
Please do not adjust margins

Please do not adjust margins
ChemComm
Page 2 of 5
View Article Online
DOI: 10.1039/C8CC04186E
COMMUNICATION
Journal Name
secondary propargylic carbonates, terminal tertiary propargylic
carbonate 1j was also working affording the corresponding tri-
substituted allene 3jb (entry 10). 1,3-Disubstituted allene 3na
(entry 13) and tetrasubstituted allene 3oa (entry 14) could also
be obtained via this Pd-catalyzed transformation.
Table 1. Ligand Screeninga
Table 3. Scope of propargylic carbonatesa
2.0 mol% Pd2(dba)3•CHCl3
8.0 mol% tri(o-tolyl)phosphine
R1
Ar
R2
R3
OCO2Me
R1
R2
R3
ArB(OH)2
+
2.0 equiv H2O, dioxane, rt, Ar
1
2
3
1.1 equiv
1
2
Entry
t (h)
Yield (%)
R1
R2
R3
Ar
1
2
n-Bu
n-Bu
n-Bu
n-Bu
n-Bu
n-Bu
n-Bu
n-Bu
Cl(CH2)4
H
Ph
H (1a)
H (1b)
H (1c)
H (1d)
Ph (2a)
Ph (2a)
Ph (2a)
Ph (2a)
Ph (2a)
Ph (2a)
Ph (2a)
Ph (2a)
Ph (2a)
1.1
94 (3aa)
91 (3ba)
94 (3ca)
93 (3da)
92 (3ea)
92 (3fa)
95 (3ga)
96 (3ha)
94 (3ia)
84 (3jb)
92 (3ka)
92 (3la)
36 (3na)
87 (3oa)
4-FC6H4
4-ClC6H4
4-BrC6H4
2.3
2.2
4.1
2.2
1.1
1.1
1.1
2.1
3
4
5
4-MeO2CC6H4 H (1e)
6
4-O2NC6H4
4-NCC6H4
3-MeOC6H4
4-ClC6H4
Me
H (1f)
H (1g)
H (1h)
H (1i)
7
8
9
10
11
12
13b
14b
Me (1j)
H (1k)
H (1l)
4-PhC6H4 (2b) 1.1
Table 2. Further optimization of reaction parameters
Allyl
4-ClC6H4
Ph
Ph (2a)
Ph (2a)
Ph (2a)
Ph (2a)
2.1
3.1
24
Allyl
H
n-C5H11
Me
H (1n)
n-Pr (1o)
n-Bu
24
a
The reaction was conducted with 1.0 mmol of 1, 1.1 mmol of 2, 2.0 mol% of
Pd2(dba)3•CHCl3, 8.0 mol% of tri(o-tolyl)phosphine, and 2.0 equiv of H2O in 2 mL of
dioxane at rt under Ar atmosphere. b The reaction was carried out at 40 oC.
The substrate scope of boronic acids with propargylic
carbonate 1a or 1m is shown in Table 4. The reaction efficiency
is not affected by the electronic nature of the aryl boronic acid.
Both electron-rich and electron-deficient arylboronic acids
gave the products in high to excellent yields. Heterocycles such
as thiophene and furan may also be incorporated in the
products 3a and 3ak. It is worth to mention that alkylboronic
acids, which have never been applied in such reactions, also
work under the optimized conditions (3ml, 3mm, 3al, 3am,
and 3an). The practicality was demonstrated by applying 6.0
mmol of 1a, affording 3ah in 93% yield under the standard
conditions (Table 4, entry 15).
Enantioenriched allenes are of high interest not only
because of their wide occurrence in natural products and
biologically active compounds but also due to their importance
in organic synthesis as chiral building blocks. We then turned
our attention to central-to-axial chirality transfer for the
synthesis of rather sensitive 1,3-diarylallenes, which were easy
to racemize in the presence of palladium catalysts.5f After
further optimization on reaction temperature (for details, see
Table S1 supporting information), we found the reaction may
proceed even at a lower temperature in a mixed solvent of
dioxane and diethyl ether affording the desired products with
a high efficiency of chirality transfer (Table 5).8 However, such
With the optimized conditions in hand, we next examined
the reaction scope. A wide range of propargylic carbonates
with different substituents at different positions all reacted
smoothly with aryl boronic acid 1a or 1b forming the
corresponding allene products with good to excellent
efficiency (Table 3). The reaction is amenable to both electron-
withdrawing and electron-donating aryl groups (R2). Various
functional groups, including halides (3ba, 3ca, 3da, and 3ia),
ester (3ea), nitro (3fa), cyano (3ga), and vinyl (3ka and 3la) are
well tolerated in the 2-alkynylic carbonates. Not only
2 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Please do not adjust margins
ChemComm
Page 3 of 5
View Article Online
DOI: 10.1039/C8CC04186E
Journal Name
COMMUNICATION
chirality transfer failed since the reaction of (S)-1m with
A mechanism is proposed as shown in Scheme 2. Pd(0)
cyclopropyl boronic acid is very sow (6% by NMR for 10 h). We would undergo SN2’-type oxidative addition with propargylic
are still working on it.
carbonates
allenylic palladium intermedate
protonated with water to generate intermediate I’ 9
1
in an anti-stereospecific manner to give the
I
. The methoxy anion was
Table 4. Scope of boronic acids with 1a or 1ma
.
Subsequently, intermediate I’ would undergo transmetalation
with the boronic acid to form the intermediate II. We reasoned
that the electron-rich and steric bulky nature of tri(o-
tolyl)phosphine ligand accelerates the oxidative addition as
well as reductive elimination10,11 to give the coupling product
3
and regenerates the catalytically active Pd(0) complex.
OCO2Me
R3
R1
R4
R3
R2
LnPd(0)
R2
1
R1
3
reductive
elimination
oxidative
addition
CO2
R3
R2
R1
R3
R1
R2
LnPd
R4
II
LnPd
OMe
I
transmetalation
H2O
R3
R2
R1
MeOH
I'
R4B(OH)2
LnPd
OH
Scheme 2. The proposed mechanism
In summary, we have developed a general and highly
efficient catalytic system for the coupling of propargylic
carbonates with commercially available aryl or alkyl boronic
acids with the commercially available tri(o-tolyl)phosphine as
ligand. The mild reaction enjoys a wide substrate scope and
functional group compatibility. In addition, excellent chirality
transfer was observed. A catalytic asymmetric protocol is in
progress in our laboratory.
Table 5. Substrate scope of chiral propargylic carbonatesa
Conflicts of interest
There are no conflicts to declare.
Acknowledgements
Financial support from the National Natural Science
Foundation of China (Grant No. 21690063) and Shanghai
Sailing Program (18YF1402000) are greatly appreciated. We
thank Mr. Xiaoyan Wu in this group for reproducing the
preparation of 3ha shown in Table 3.
Notes and references
1
(1) For a most recent monograph, see: Modern Allene
Chemistry, ed. N. Krause, A. S. K. Hashmi, Wiley-VCH,
Weinheim, 2004, vols 1 and 2.
2
For selected reviews, see: (a) F. López, J. L. Mascareñas,
Chem. Soc. Rev., 2014, 43, 2904. (b) J. Ye, S. Ma, Acc. Chem.
Res., 2014, 47, 989. (c) T. Lu, Z. Lu, Z.-X. Ma, Y Zhang, R. P.
Hsung, Chem. Rev., 2013, 113, 4862. (d) S. Yu, S Ma, Angew.
Chem., Int. Ed., 2012, 51, 3074. (e) S. Ma, Acc. Chem. Res.,
2009, 42, 1679. (f) M. Brasholz, H.-U. Reissig, R. Zimmer, Acc.
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 3
Please do not adjust margins

Please do not adjust margins
ChemComm
Page 4 of 5
View Article Online
DOI: 10.1039/C8CC04186E
COMMUNICATION
Journal Name
Chem. Res., 2009, 42, 45. (g) S. Ma, Aldrichimica Acta, 2007
40, 91. (h) S. Ma, Chem. Rev., 2005, 105, 2829. (i) A.
Hoffmann-Röder, N. Krause, Angew. Chem., Int. Ed., 2004
,
,
43, 1196. (j) L. K. Sydnes, Chem. Rev., 2003, 103, 1133. (k) S.
Ma, Acc. Chem. Res., 2003, 36, 701.
3
For reviews on the synthesis of allenes, see: (a) Chapters 1–8
in ref. 1. (b) R. K. Neff, D. E. Frantz, ACS Catal., 2014, 4, 519.
(c) S. Yu, S. Ma, Chem. Commun., 2011, 5384. (d) M.
Ogasawara, Tetrahedron: Asymmetry, 2009, 20, 259. (e) K.
M. Brummond, J. E. DeForrest, Synthesis, 2007, 795. (f) G. B.
Hammond, ACS Symp. Ser., 2005, 911,204.(g) N. Krause, A.
Hoffmann-Röder, Tetrahedron, 2004, 60, 11671.
4
5
For reviews, see: (a) S. Ma, Eur. J. Org. Chem., 2004, 1175. (b)
C. Bruneau, C. Darcel, P. H. Dixneuf, Curr. Org. Chem., 1997,
1, 197.
(a) T. Moriya, N. Miyaura, A. Suzuki, Synlett, 1994, 149. (b)
M. Ishikura, I. Agata, Heterocycles, 1996, 43, 1591. (c) M.
Ishikura, Y. Matsuzaki, I. Agata, N. Katagiri, Tetrahedron,
1998
Tetrahedron Lett., 2004, 45, 5573. (e) M. Yoshida, H. Ueda,
M. Ihara, Tetrahedron Lett., 2005 46, 6705. (f) G. A.
Molander, E. M. Sommers, S. R. Baker, J. Org. Chem., 2006
, 54, 13929. (d) M. Yoshida, T. Gotou, M. Ihara,
,
,
71, 1563. (g) M. Yoshida, T Okada, K. Shishido, Tetrahedron,
2007, 63, 6996. (h) C. Wang, L. Kong, Y. Li, Y. Li, Eur. J. Org.
Chem., 2014, 3556. (i) H. Luo, Y. Yu, S. Ma, Org. Chem. Front.,
2016, 3, 1705.
6
For selective generation of alkynes, see: (a) I. Matsuda, K.
Komori, K. Itoh, J. Am. Chem. Soc., 2002, 124, 9072. (b) M. J.
Ardolino, J. P. Morken, J. Am. Chem. Soc., 2012, 134, 8770.
(c) I. Ambrogio, S. Cacchi, G. Fabrizi, A. Goggiamani, A.
Iazzetti, Eur. J. Org. Chem., 2015, 3147. (d) X. Huang, S. Wu,
W. Wu, P. Li, C. Fu, S. Ma, Nat. Commun., 2016, 7, 12382. (e)
S. Ma, A. Zhang, J. Org. Chem., 2002, 67, 2287.
7
8
P. Li, B. Lü, C. Fu, S. Ma, Adv. Synth. Catal., 2013, 355, 1255.
The absolute configuration of (S)-3ko was established by
comparing the optical rotation of the exactly same
compound in refe. 5(i).
9
For a selected review, see: (a) A. J. J. Alastair and G. C. Lloyd-
Jones, Chem. Soc. Rev., 2014, 43, 412. For selected examples:
(b) C. Amatore, A. Jutand and G. Le Duc, Chem. Eur. J., 2011
,
17, 2492. (c) B. P. Carrow and J. F. Hartwig, J. Am. Chem.
Soc., 2011, 133, 2116. (d) A. F. Schmidt, A. A. Kurokhtina and
E. V. Larina, Russ. J. Gen. Chem., 2011, 81, 1573.
10 For selected reviews, see: (a) U. Christmann, R. Vilar, Angew.
Chem., Int. Ed., 2005, 44, 366. (b) D. S. Surry, S. L. Buchwald,
Angew. Chem., Int. Ed., 2008, 47, 6338. (c) V. V. Grushin and
H. Alper, Chem. Rev., 1994, 94, 1047. For a selected book,
see: (d) New Trends in Cross-Coupling: Theory and
Applications, ed. T. J. Colacot, The Royal Society of Chemistry,
2015
.
11 For some of the typical examples, see: (e) W. O. David, J. P.
Wolfe and S. L. Buchwald, J. Am. Chem. Soc., 1998, 120,
9722. (f) F. Rataboul, A. Zapf, R. Jackstell, S. Harkal, T.
Riermeier, A. Monsees, U. Dingerdissen, M. Beller, Chem.
Eur. J. 2004, 10, 2983. (g) N. Kataoka, Q. Shelby, J. P.
Stambuli, J. F. Hartwig, J. Org. Chem. 2002, 67, 5553. (h) F. Y.
Kwong, W. H. Lam, C. H. Yeung, K. S. Chan, A. S. C. Chan,
Chem. Commun., 2004, 1922. (i) G. J. Withbroe, R. A. Singer,
J. E.Sieser, Org. Process Res. Dev. 2008, 12, 480. (j) B. Lü, C.
Fu, S. Ma, Tetrahedron Lett.2010, 51, 1284.
4 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Please do not adjust margins
ChemComm
Page 5 of 5
View Article Online
DOI: 10.1039/C8CC04186E
Journal Name
COMMUNICATION
Graphic abstract
Tri(o-tolyl)phosphine has been identified as the highly
efficient ligand for Pd-catalyzed coupling of propargylic
carbonates with different types of organo boronic acids at
room temperature.
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 5
Please do not adjust margins