Highly Regio- and Enantioselective Alkoxycarbonylative Amination of Terminal Allenes Catalyzed by a Spiroketal-Based Diphosphine/Pd(II) Complex

Article abstract of DOI:10.1021/jacs.5b07764

An enantioselective alkoxycarbonylation-amination cascade process of terminal allenes with CO, methanol, and arylamines has been developed. It proceeds under mild conditions (room temperature, ambient pressure CO) via oxidative Pd(II) catalysis using an aromatic spiroketal-based diphosphine (SKP) as a chiral ligand and a Cu(II) salt as an oxidant and affords a wide range of α-methylene-β-arylamino acid esters (36 examples) in good yields with excellent enantioselectivity (up to 96% ee) and high regioselectivity (branched/linear > 92:8). Preliminary mechanistic studies suggested that the reaction is likely to proceed through alkoxycarbonylpalladation of the allene followed by an amination process. The synthetic utility of the protocol is showcased in the asymmetric construction of a cycloheptene-fused chiral β-lactam.

Full text of DOI:10.1021/jacs.5b07764

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Communication
Highly Regio- and Enantioselective Alkoxycarbonylative
Amination of Terminal Allenes Catalyzed by SKP/Pd(II) Complex
Jiawang Liu, Zhaobin Han, Xiaoming Wang, Zheng Wang, and Kuiling Ding
J. Am. Chem. Soc., Just Accepted Manuscript • DOI: 10.1021/jacs.5b07764 • Publication Date (Web): 17 Sep 2015
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Highly Regioꢀ and Enantioselective Alkoxycarbonylative Amination
of Terminal Allenes Catalyzed by SKP/Pd(II) Complex
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Jiawang Liu, Zhaobin Han, Xiaoming Wang, Zheng Wang* and Kuiling Ding*†
State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences,
345 Lingling Road, Shanghai 200032; China
†and Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), China
Supporting Information Placeholder
ABSTRACT: An enantioselective alkoxycarbonylationꢀ
amination cascade process of terminal allene with CO, methanol
and arylamine has been developed under mild conditions (rt, amꢀ
bient pressure CO) via oxidative Pd(II) catalysis using an aroꢀ
matic spiroketalꢀbased diphosphine (SKP) as chiral ligand and
Cu(II) salt as oxidant, affording a wide range of αꢀmethleneꢀβꢀ
arylamino acid esters (36 examples) in good yields with excellent
enantioselectivity (up to 96% ee) and high regioselectivity
(branched/linear > 92:8). Preliminary mechanistic studies sugꢀ
gested that the reaction is likely to proceed through alkoxylcarꢀ
bonyl palladation of the allene followed by an amination process.
The synthetic utility of the protocol is showcased in the asymmetꢀ
ric construction of a cyclohepteneꢀfused chiral βꢀlactam.
Recently we reported a Pd(0)ꢀcatalyzed asymmetric allylic
amination of racemic MoritaꢀBaylis–Hillman (MBH) adducts,
Allenes have been recognized as versatile building blocks in
organic synthesis,1 enabling numerous efficient transformations
wherein an aromatic spiroketalꢀbased bisphosphine ligand
(SKP)10 demonstrated excellent control of regioꢀ and enantioseꢀ
lectivity.11 Mechanistic studies revealed that SKP ligand plays a
bifunctional role in the catalysis, forming a CꢀP σꢀbond with the
terminal carbon of allyl moiety and concomitantly coordinating
with Pd in the key catalytic species (Scheme 1b).12 We envisaged
such a phosphoniumꢀPd(II) species might be generated via an
alternative route, i.e., by alkoxycarbonyl palladation of allenes
with CO and alcohol as acylating agent via oxidative Pd(II) catalꢀ
ysis (Scheme 1a).13 This would effectively steer the course of the
catalysis through the same key Pd species, allowing for a more
straightforward access to chiral αꢀmethleneꢀβꢀarylamino acid
esters14 by obviating the tedious synthesis of MBH adducts.
Though some studies have exploited Pd(II)ꢀcatalyzed oxidative
carbonylation15 of allenes to generate an 2ꢀalkoxycarbonyl πꢀ
allylpalladium species in harness with attack by a nucleophile,16
no asymmetric variant has been reported so far to our knowledge.
Initial studies were focused on examining the feasibility of the
strategy and optimizing the reaction conditions, using 1ꢀ
phenylallene 1a and aniline 2a as model substrates. The reactions
were generally run at rt for 24 h under balloon pressure of CO in
MeOH or MeOHꢀcontaining solvent, with a Pd(II) salt (10 mol%)
and a chiral diphosphine (12 mol%) as the catalyst and Et3N (4.0
equiv) as the base. As shown in Table 1, the reaction catalyzed by
PdCl2/(S,S,S)ꢀSKP in methanol gave the branched regioisomer
3aa in only 7% yield in 24 h (entry 1), probably owing to the
absence of a stoichiometric oxidant necessary for Pd(II) regeneraꢀ
tion from Pd(0) species reduced in amination step. Introduction of
3.0 equiv of CuCl2 as an oxidant led to an increased yield (19%)
of 3aa, albeit with poor branched/linear (3aa/4aa) ratio and ee
for rapid generation of molecular complexity.2 The unique reacꢀ
tivity of the 1,2ꢀdiene structure renders allenes excellent flexibilꢀ
ity to perform multicomponent or tandem reactions, providing
elegant access to multifunctional molecules from readily available
chemicals.3 In this context, a typical mode for transition metal
catalyzed allene transformation involves insertion into RꢀM bond
(hydridoꢀ, carboꢀ, acylꢀ, or elementoꢀM in nature), to generate a
transient πꢀallylꢀM species that is trapped by an external or interꢀ
nal nucleophile, furnishing various functionalized olefins or cyclic
compounds.2,3 In the past two decades, this powerful strategy has
been successfully extended to enantioselective functionalization
of allenes4 via asymmetric Pd,5 Rh,6 or Ni7 catalysis. Despite the
remarkable progresses, however, significant challenges still reꢀ
main in the control of chemoꢀ, regioꢀ, and enantioselectivities, as
multiple reactivities can be invoked on the two orthogonal cumuꢀ
lated C=C bonds in the catalysis.2,3a,4,8 From synthetic perspective,
development of new enantioselective tandem processes for allene
functionalization, which can selectively combine several comꢀ
pounds in oneꢀpot is a soughtꢀafter chemistry,9 which holds the
promise for rapid construction of chiral complex molecules withꢀ
out arduous and wasteful intermediate isolation in a multistep
synthesis. Herein, we report the first regioꢀ and enantioselective
difunctionalization of simple terminal allenes with CO, methanol
and arylamines, via a SKP/Pd(II)ꢀcatalyzed tandem alkoxycarꢀ
bonylative amination process.
Scheme 1. Reaction Design
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(entry 2). Cu(OAc)2 proved to be superior to CuCl2 in this reacꢀ
ed 3aa in moderate 71% (entry 11), and extending the reaction
time to 96 h afforded 3aa in 87% yield with a 96:4 B/L ratio and
94% ee [entry 12, defined as condition B].
tion, affording preferentially branched product 3aa in 52% yield
with 74% ee (entry 3). Presumably, partial exchange of the acetate
with the chloride in PdCl2 gave coordinated acetate anions, which
can serve as an internal base to facilitate the formation of a pallaꢀ
dium alkoxide intermediate.13a Indeed, the beneficial effect of
acetate was further corroborated with the use of Pd(OAc)2 as
Pd(II) source, whereby 3aa was obtained in significantly enꢀ
hanced yield (73%) with 89% ee and 95:5 branched selectivity
(entry 4). After an extensive screening of reaction parameters
(solvent, CO pressure, base, termꢀ
Table 2. Substrate Scope Study for Allenes
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NH
NH
NH
NH
CO2Me
CO2Me
CO2Me
CO2Me
Table 1. Methoxycarbonylative Amination of 1ꢀ
Phenylallene (1a) with Aniline (2a), CO and MeOH a
MeO
3cab
F
3dab (93%), 91% ee
3/4: 95:5
3aa (87%), 94% ee
3ba (93%), 91% ee
(92%), 90% ee
3 4
3 4
/
/
: 96:4
: 96:4
3/4: 97:3
NH
NH
NH
NH
CO2Me
CO2Me
CO2Me
CO2Me
Br
Cl
3hab
(88%), 93% ee
3ea
3ga
(87%), 90% ee
3 4
(82%), 92% ee
3 4
3fa
(88%), 93% ee
3 4
3 4
: 94:6
/
/
: 94:6
/ : 93:7
/
: 95:5
NH
NH
NH
NH
CO2Me
CO2Me
CO2Me
Cl
CO2Me
Entry
1e
2e
3e
4e
[Pd]/ligand
[O]
3aa/4aab
36:64
50:50
81:19
95:5
Yield(%)c
Ee(%)d
N.D.
40
BnO
3kab
(93%), 90% ee
3la (50%), 93% ee
3/4: 93:7
3ja (85%), 92% ee
3/4: 96:4
3ia (83%), 93% ee
3 4
PdCl2/(S,S,S)ꢀSKP
PdCl2/(S,S,S)ꢀSKP
PdCl2/(S,S,S)ꢀSKP
Pd(OAc)2/(S,S,S)ꢀSKP
Pd(OAc)2/(S,S,S)ꢀSKP
Pd(OAc)2/(S,S,S)ꢀSKP
Pd(OAc)2/(R)ꢀBINAP
none
7
3 4
/
: 97:3
/
: 96:4
CuCl2
19
52
73
89
93
54
68
5
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
74
NH
NH
NH
NH
CO2Me
TBSO
CO2Me
MeO2C
CO2Me
CO2Me
89
11
3
5
5
6f
96:4
92
3mab
(71%), 92% ee
3oab
(78%), 92% ee
3/4
3pab
3na (81%), 87% ee
3/4
(80%), 92% ee
3/4
96:4
93
3/4: 95:5
: >95:5
: >95:5
: >95:5
7
64:36
79:21
24:76
72:28
95:5
3
a Unless otherwise noted, the reactions were performed under condition B. The
data in parentheses are the yields of isolated 3. In each case, the branched/linear
ratio of 3:4 was determined by 1H NMR analysis of crude product, while the ee
value of 3 was determined by chiral HPLC. Reactions were conducted under
condition A.
8
Pd(OAc)2/(R)ꢀSEGPhos Cu(OAc)2
49
9
Pd(OAc)2/(R)ꢀSDP
Cu(OAc)2
5
b
10
11g
12g,h
Pd(OAc)2/Trost ligand
Pd(OAc)2/(S,S,S)ꢀSKP
Pd(OAc)2/(S,S,S)ꢀSKP
Cu(OAc)2
<5
71
87
37
Cu(OCOEt)2
92
Cu(OCOEt)2
96:4
94
The substrate scope of allenes for the SKP/Pd(OAc)2 cataꢀ
lyzed reaction was first examined using aniline (2a) as the nucleꢀ
ophile. In most cases, the reactions were conducted under condiꢀ
tion B, and the results were summarized in Table 2. The reaction
appears to be quite compatible with various types of terminal
allenes (1aꢀp), consistently afforded the corresponding allylic
amine products 3aaꢀ3pa in good to excellent yields (up to 93%),
high branched regioselectivities (>93/7), and excellent enantioseꢀ
lectivities (87ꢀ94% ee), irrespective of whether aromatic (1aꢀk) or
aliphatic (1lꢀp) substituents are tethered to the terminus of the
allenes. The allenes bearing alkyl substituents on oꢀ, mꢀ or pꢀ
position of the phenyl terminus gave the corresponding products
(3ba, 3ea, 3fa) in similar yields and selectivities, and functional
groups such as TBSO (3pa) or halides (3da, 3ga, 3ha, 3ia) were
well tolerated in the catalysis. It is noteworthy that the present
SKP/Pd(II) catalyzed process has effectively overcome some
intrinsic limitations in aforementioned SKP/Pd(0) catalyzed alꢀ
lylic amination route to products 3, whereby the presence of both
1ꢀaryl and 2ꢀCO2Et groups in the allylic acetate substrates have
been found crucial for the reactivity, and hence the products were
confined to 3 bearing a βꢀaryl group.11,12 Finally, the absolute
configuration of 3ha was established to be R by Xꢀray crystal
diffractional analysis.
a Unless otherwise noted, all reactions were performed under 1 atm CO at rt for
24 h in the presence of 1a (0.25 mmol), 2a (0.75 mmol), [Pd] (10 mol%),
ligand (12 mol%), Cu(II) salt (0.75 mmol), and Et3N (1.0 mmol), in a solvent
mixture of methanol and fluorobenzene (2.5 mL, 9/1 v/v). b Determined by 1H
e
c
d
NMR analysis. Yield of the isolated 3aa. Determined by chiral HPLC.
Methanol (2.5 mL) as solvent. f 40 h. g [Pd] (5 mol%), SKP (6 mol%). h 96 h.
inal oxidant, temperature, Pd precursor, etc) (for details, see Taꢀ
bles S1ꢀS9 in SI), a solvent mixture of MeOH/PhF (9:1 v/v) was
identified to be optimal, to give 3aa in 89% yield with 92% ee
and 96:4 B/L ratio (entry 5). This is in sharp contrast with the
Pd(0)/SKP catalyzed asymmetric allylic amination of MBH aceꢀ
tates,11 wherein CH2Cl2 was optimal but CH3OH was poor for
catalysis. This distinction clearly indicated that different mechaꢀ
nistic details are present in the Pd(0)/SKP and Pd(II)/SKP routes
to 3aa/4aa, also reflected the need of high CH3OH concentration
in the present catalysis (for catalyst activation). Further prolongꢀ
ing the reaction time from 24 to 40 h resulted in a slight imꢀ
provement in yield of 3aa (entry 6), and this set of conditions
were identified as condition A in subsequent studies. Several
other privileged chiral diphosphine ligands17 were also evaluated
in the catalysis, unfortunately all afforded less satisfactory results
(entries 7–10). Some SKP ligands with different PAr2 moieties
were also found workable in the catalysis, but none showed sigꢀ
nificant improvement in activity or selectivities (Table S8 in SI).
The use of 3.0 equiv of copper propionate [Cu(OCOEt)2] as the
oxidant at a reduced loading of SKP/Pd(OAc)2 (5 mol %) affordꢀ
Table 3. Substrate Scope Study for Arylamines
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groups, which underwent RCM with 2nd generation Grubbs cataꢀ
lyst19 to give βꢀlactam 9 in overall yield of 50% over five steps
with 93% ee.
5
6
Scheme 2. Synthetic Transformation of (R)ꢀ3pa into βꢀ
Lactam 9
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Reagents and conditions: i) Sn[N(TMS)2]2, toluene, reflux, 12h, 93%; ii) n-
Bu4NF, 0°Cꢀrt, 6 h, 95%; iii) SO3.Pyr, DMSO, NEt3, CH2Cl2, 0°Cꢀrt, 8 h, 88%;
iv) Ph3PMeBr, n-BuLi, THF, 0°Cꢀrt, 10 h, 80%; v) Grubbs catalyst 2nd generaꢀ
tion, nꢀhexane, 55°C, 6 h, 79%.
While the exact mechanism of the titled catalysis is not clear
at this stage, the results from a series of comparative studies (for
details, see SI) seem to be consistent with the proposed catalytic
cycle in Scheme 3. Herein the catalysis is likely to be initiated by
a transꢀ[(SKP)(AcO)PdꢀCOOMe] species B, generated via exꢀ
change of OAc in the [(SKP)Pd(OAc)2] (A) with methoxy group
followed by carbonyl insertion. Methoxycarbonylpalladation of
allene 1a by intermediate B, followed by intramolecular rearꢀ
rangement would give the phosphoniumꢀPd(II) species C, which
is the same key intermediate in the mechanism for SKP/Pd(0)
catalyzed allylic amination of MBH acetates reported previously
by our group.12 The following ligand exchange of intermediate C
with the amido from aniline is expected to be fast under basic
conditions, affording the amidoꢀPd(II) species D. Reductive elimꢀ
ination of D followed by an intramolecular Pdꢀassisted phosphoꢀ
nium dissociation furnishes the product 3aa, with concomitant
release of (SKP)Pd(0) species E. Oxidation of E by a Cu(II) salt
regenerates the active Pd(II) species A, thus accomplishing the
catalytic cycle. It is noteworthy that clear distinctions exist in the
courses to the intermediate C for SKP/Pd(II)ꢀcatalyzed methoxꢀ
ycarbonylative amination of allenes and SKP/Pd(0) catalyzed
allylic amination of MBH acetates. Control experiments using
Hg(0) test suggested Pd(0) reoxidation tends to be sluggish in the
catalytic cycle, and a significant fraction of Pd species lay
dormant as Pd(0) in the system, which may account for relatively
high catalyst loading needed in the Pd(II) catalysis.
a Unless otherwise noted, the reactions were performed under condition B. The
data in parentheses are the yields of isolated 3. In each case, the branched/linear
ratio of 3:4 was determined by 1H NMR analysis of crude product, while the ee
b
value of 3 was determined by chiral HPLC. Reactions were conducted under
c
condition A. The reaction was conducted under condition B using EtOH
instead of MeOH.
A survey of various arylamines (2aꢀr) in the reactions with
several terminal allenes (1a, 1k, or 1q), CO, and MeOH was also
performed (Table 3). Substituents on the arylamines seemed to
have no impact on the SKP/Pd(OAc)2 catalysis, as both electronꢀ
rich and electronꢀpoor arylamines were compatible with the proꢀ
cedure, and a broad functional group tolerance was observed in
the reaction. The reactions of arylamines bearing F, Cl, Br, acyl,
MeO, MeS, hydroxyalkyl, or vinyl substituent proceeded smoothꢀ
ly under condition B or A, to provide the corresponding products
3abꢀ3ar, 3qi, and 3aa’ in good yields (up to 95%), high B/L ratiꢀ
os (>94/6), and excellent ee values (up to 96%). Notably, product
3kd as a synthetic intermediate for chiral drug Ezetimibe was
obtained in good yield with high regioselectivity (98/2) and enanꢀ
tioselectivity (90% ee) using condition A. Preliminary studies on
reactions involving other types of amines and allenes afforded less
satisfactory results (SI), suggesting a large space for future develꢀ
opment.
Scheme 3. A Plausible Mechanism
The synthetic utility of the methodology was exemplified in the
asymmetric construction of 9, a useful cyclohepteneꢀfused chiral
βꢀlactam.18 As shown in Scheme 2, (R)ꢀ3pa, obtained in 80%
yield and 92% ee from a gramꢀscale synthesis (SI) using the preꢀ
sent protocol, was treated with Sn[N(TMS)2]2 to give the silylꢀ
protected βꢀlactam 5. Deprotection of 5 using TBAF afforded
alcohol 6, which on Swern oxidation furnished aldehyde 7. Wittig
methylenation afforded βꢀlactam 8 with two terminal alkene
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[2](a) Zimmer, R.; Dinesh, C. U.; Nandanan, E.; Khan, F. A. Chem.
Rev.2000,100, 3067; (b) Lechel, T.; Pfrengle, F.; Reissig, H. U.; Zimmer,
R. ChemCatChem, 2013, 5, 2100.
[3] (a) Jeganmohan, M.; Cheng, C.ꢀH. Chem. Commun. 2008, 3101.
(b)Jonasson, C.; Horvath, A.; Backvall, J. E. J. Am. Chem. Soc. 2000, 122,
9600; (c) Tonogaki, K.; Itami, K.; Yoshida, J. J. Am. Chem. Soc. 2006,
128, 1464.
8
[4] Yu, S.; Ma, S. Angew. Chem. Int. Ed. 2012, 51, 3074.
9
[5] (a) Larock, R. C.; Zenner, J. M. J. Org. Chem. 1995, 60, 482; (b)
Trost, B. M.; Jakel, C.; Plietker, B. J. Am. Chem. Soc. 2003, 125, 4438; (c)
Pelz, N. F.; Woodward, A. R.; Burks, H. E.; Sieber, J. D.; Morken, J. P. J.
Am. Chem. Soc. 2004, 126, 16328; (d) Ohmura, T.; Taniguchi, H.;
Suginome, M. J. Am. Chem. Soc. 2006, 128, 13682; (e) Shu, W.; Ma, S.
Chem. Commun. 2009, 6198.
10
11
12
13
14
15
16
17
18
19
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22
23
24
25
26
27
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42
43
44
45
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48
49
50
51
52
53
54
55
56
57
58
59
60
[6] (a) Koschker, P.; Lumbroso, A.; Breit, B. J. Am. Chem. Soc. 2011,
133, 20746; (b) Cooke, M. L.; Xu, K.; Breit, B. Angew. Chem. Int. Ed.
2012, 51, 10876; (c) Li, C.; Kahny, M.; Breit, B. Angew. Chem. Int. Ed.
2014, 53, 13780; (d) Xu, K.; Thieme, N.; Breit, B. Angew. Chem. Int. Ed.
2014, 53, 2162; (e) Pritzius, A. B.; Breit, B. Angew. Chem. Int. Ed. 2015,
54, 3121.
[7] (a) Miura, T.; Morimoto, M.; Murakami, M. J. Am. Chem. Soc. 2010,
132, 15836; (b) Yamauchi, M.; Morimoto, M.; Miura, T.; Murakami, M.
J. Am. Chem. Soc. 2010, 132, 54.
[8] Hashmi, A. S. K. Angew. Chem. Int. Ed. 2000, 39, 3590.
In conclusion, we have developed the first highly chemoꢀ, reꢀ
gioꢀ and enantioselective alkoxycarbonylationꢀamination cascade
process of terminal allenes with arylamines, carbon monoxide and
methanol, via oxidative SKP/Pd(II) catalysis with a Cu(II) salt as
oxidant, affording a range of βꢀarylꢀβꢀarylamineꢀαꢀmethyleneꢀ
carboxylic acid derivatives in good yields with excellent regioꢀ
and enantioselectivities (B/L > 92:8, up to 96% ee) with a broad
substrate scope. Preliminary mechanistic studies suggested that
the reaction is likely to proceed through alkoxylcarbonyl palladaꢀ
tion of the allene followed by an amination process. The synthetic
utility of the protocol is exemplified in the asymmetric construcꢀ
tion of a cyclohepteneꢀfused chiral βꢀlactam. We anticipate that
the strategy of present Pdꢀcatalyzed cascade process may find
wider applications in the efficient synthesis of multifunctional
compounds starting from simple olefinic molecules.
[9] (a) Ramon, D. J.; Yus, M. Angew. Chem. Int. Ed. 2005, 44, 1602; (b)
Burks, H. E.; Morken, J. P. Chem. Commun. 2007, 4717.
[10] (a) Wang, X.; Han, Z.; Wang, Z.; Ding, K. Angew. Chem. Int. Ed.
2012, 51, 936; (b) Wang, X.; Guo, P.; Wang, X.; Wang, Z.; Ding, K. Adv.
Synth. Catal. 2013, 355, 2900; (c) Cao, Z.ꢀY.; Wang, X.; Tan C.; Zhao,
X.ꢀL.; Zhou, J.; Ding, K. J. Am. Chem. Soc. 2013, 135, 8197; (d) Miyazaki,
Y.; Ohta, N.; Semba, K.; Nakao, Y. J. Am. Chem. Soc. 2014, 136, 3732.
For selected reviews on the uses of chiral spiro ligands in asymmetric
catalysis, see: (e) Xie, J.ꢀH.; Zhou, Q.ꢀL. Acc. Chem. Res. 2008, 41, 581;
(f) Ding, K.; Han, Z.; Wang, Z. Chem. Asian J. 2009, 4, 32.
[11] Wang, X.; Meng, F.; Wang, Y.; Han, Z.; Chen, Y.; Liu, L.; Wang, Z.;
Ding, K. Angew. Chem. Int. Ed. 2012, 51, 9276.
[12] Wang, X.; Guo, P.; Han, Z.; Wang, X.; Wang, Z.; Ding, K. J. Am.
Chem. Soc. 2014, 136, 405.
[13] For reviews, see: (a) Stahl, S. S. Angew. Chem. Int. Ed. 2004, 43,
3400; (b) Beccalli, E. M.; Broggini, G.; Martinelli, M.; Sottocornola, S.
Chem. Rev. 2007, 107, 5318; (c) McDonald, R. I.; Liu, G. S.; Stahl, S. S.
Chem. Rev. 2011, 111, 2981.
ASSOCIATED CONTENT
Supporting Information
[14] For an elegant example, see: Yukawa, T.; Seelig, B.; Xu, Y.ꢀJ.;
Morimoto, H.; Matsunaga, S.; Berkessel, A.; Shibasaki, M. J. Am. Chem.
Soc. 2010, 132, 11988.
Synthetic procedures, characterization and additional data. This
material is available free of charge via the Internet at
http://pubs.acs.org.
[15] For reviews, see: (a) Gabriele, B.; Salerno, G.; Costa, M. Top. Or-
ganomet. Chem. 2006, 18, 239; (b) Wu, X. F.; Neumann, H.; Beller, M.
ChemSusChem, 2013, 6, 229.
AUTHOR INFORMATION
Corresponding Author
kding@mail.sioc.ac.cn
[16] (a) Alper, H.; Hartstock, F. W.; Despeyroux, B. J. Chem. Soc., Chem.
Commun. 1984, 905; (b) Shaw, R.; Lathbury, D.; Anderson, M.; Galꢀ
lagher, T. J. Chem. Soc., Perkin Trans. 1, 1991, 659; (c) Grigg, R.; Pratt,
R. Tetrahedron Lett. 1997, 38, 4489; (d) Okuro, K.; Alper, H. J. Org.
Chem. 1997, 62, 1566; (e) Grigg, R.; Monteith, M.; Sridharan, V.; Terrier,
C. Tetrahedron, 1998, 54, 3885; (f) Xiao, W. J.; Vasapollo, G.; Alper, H.
J. Org. Chem. 1998, 63, 2609; (g) Grigg, R.; MacLachlan, W.; Rasparini,
M. Chem. Commun. 2000, 2241; (h) Wang, L.; Wang, Y. X.; Liu, C.; Lei,
A. W. Angew. Chem. Int. Ed. 2014, 53, 5657; (i) Liu, J.; Liu, Q.; Franke,
R.; Jackstell, R.; Beller, M. J. Am. Chem. Soc. 2015, 137, 8556.
ACKNOWLEDGMENT
We are grateful for financial support from National Natural Sciꢀ
ence Foundation of China (21232009, 20421091, 21172237), the
Chinese Academy of Sciences, and the Science and Technology
Commission of Shanghai Municipality.
[17] (a) Privileged Chiral Ligandsand Catalysts, Ed. Zhou, Q.ꢀL.; Wileyꢀ
VCH, Weinheim, 2011; (b) Xie, J.ꢀH.; Zhou, Q.ꢀL. Acta Chim. Sinica
2014, 72, 778.
REFERENCES
[1] Modern Allene Chemistry, ed. Krause, N and Hashmi, A. S. K.;
WileyꢀVCH, Weinheim, 2004.
[18] Grainger, R. S.; Betou, M.; Male, L.; Pitak, M. B.; Coles, S. J. Org.
Lett. 2012, 14, 2234.
[19] Scholl, M.; Ding, S.; Lee, C. W.; Grubbs, R. H. Org. Lett. 1999, 1
953.
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