Direct catalytic enantio- and diastereoselective Mannich reaction of isocyanoacetates and ketimines

Article abstract of DOI:10.1002/anie.201309719

A catalytic asymmetric synthesis of imidazolines with a fully substituted β-carbon atom by a Mannich-type addition/cyclization reaction of isocyanoacetate pronucleophiles and N-diphenylphosphinoyl ketimines has been developed. When a combination of a cinchona-derived aminophosphine precatalyst and silver oxide was employed as a binary catalyst system, good reactivity, high diastereoselectivities (up to 99:1 d.r.), and excellent enantioselectivities (up to 99 % ee) were obtained for a range of substrates. Binary catalyst system: A catalytic asymmetric synthesis of imidazolines with a fully substituted β-carbon atom through a Mannich-type addition/cyclization reaction of isocyanoacetate pronucleophiles and N-diphenylphosphinoyl ketimines has been developed. By employing a cinchona-derived aminophosphine precatalyst and silver oxide as a binary catalyst system, good reactivity and high diastereo- and enantioselectivities were obtained.

Full text of DOI:10.1002/anie.201309719

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Angewandte
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DOI: 10.1002/anie.201309719
Asymmetric Synthesis
Direct Catalytic Enantio- and Diastereoselective Mannich Reaction of
Isocyanoacetates and Ketimines**
Irene Ortꢀn and Darren J. Dixon*
Abstract: A catalytic asymmetric synthesis of imidazolines
with a fully substituted b-carbon atom by a Mannich-type
addition/cyclization reaction of isocyanoacetate pronucleo-
philes and N-diphenylphosphinoyl ketimines has been devel-
oped. When a combination of a cinchona-derived amino-
phosphine precatalyst and silver oxide was employed as
a binary catalyst system, good reactivity, high diastereoselec-
tivities (up to 99:1 d.r.), and excellent enantioselectivities (up to
99% ee) were obtained for a range of substrates.
systems have been reported.[6] To date, however, only
aldimines have been employed, and the analogous asymmet-
ric transformation of the significantly less reactive keti-
mines[10] has not been reported despite its potential to provide
a direct route to chiral imidazolines that possess vicinal
stereogenic centers, including a fully substituted b-carbon
atom.
Recently, our group reported the highly enantio- and
diastereoselective synthesis of oxazolines[11] from isocyanoa-
cetate pronucleophiles and aldehydes using a binary catalyst
system that combines “soft” metal ions and cinchona-derived
aminophosphine precatalysts 1.[12] To promote reactivity and
govern selectivity in a cooperative fashion with metal ion
additives, these precatalysts possess Brønsted basic, Lewis
basic, and hydrogen-bond-donor groups that are situated in
close proximity around a chiral pocket that is created by the
cinchona scaffold (Figure 1). We believed that a true test of
S
tereochemically defined a,b-diaminoacids are important
structural motifs that are contained within many bioactive
natural compounds.[1] This abundance has stimulated the
development of methods towards their stereoselective con-
struction; a common approach is based on catalytic asym-
metric Mannich-type reactions of derivatives[2,3] of or pre-
cursors[4] to a-amino acids. The vast majority of these methods
have targeted structures that possess a tertiary stereocenter at
the b-position through additions to aldimines.[2,3] Reports of
catalytic asymmetric methods that afford derivatives possess-
ing a fully substituted stereocenter at the b-position are rare.[5]
However, in work relevant to this study, Matsunaga and
Shibasaki employed ketimine electrophiles in Mannich reac-
tions with isothiocyanoato esters to afford cyclic tetrasubsti-
tuted thiourea derivatives with high selectivities.[5a]
Figure 1. Structure, design, and features of multifunctional aminophos-
phine precatalysts 1a and 1b. TS=transition state.
A complementary and practical route to a,b-diaminoacids
proceeds via imidazoline heterocycles, which may be directly
formed by catalytic asymmetric Mannich-type addition/cyc-
lization reactions of isocyanoester pronucleophiles with imine
electrophiles.[6,4p] The reactants are readily prepared on
a large scale, and the imidazoline products, unlike cyclic
thioureas, are readily converted into target a,b-diaminoacids
through standard hydrolytic or reductive manipulation.[7]
Furthermore, imidazolines form the structural core of many
biologically active compounds,[8] and they are useful building
blocks for the synthesis of cyclopalladated complexes, chiral
catalysts, and chiral solvating agents.[9] Highly stereoselective
syntheses using either metal-based or metal-free catalyst
the utility of this catalyst system was to attain new reactivity
and stereocontrol in challenging reactions for which no
precedent exists. The catalytic asymmetric Mannich-type
addition/cyclization reaction of isocyanoester pronucleophi-
les I with ketimines II to afford imidazolines III, which
possess a fully substituted stereocenter at the b-carbon atom
(Scheme 1), indeed provided this opportunity, and herein we
present our findings.
Initial proof-of-concept studies were performed with
readily prepared diphenylmethylisocyanoacetate (2a) as the
pronucleophile and N-diphenylphosphinoyl (DPP)-protected
and acetophenone-derived imine 3a. Such imines are readily
prepared from the parent ketone, and subsequent cleavage of
the DPP group of imidazolines 4 was anticipated to be clean
and efficient under mildly acidic conditions.[13]
[*] Dr. I. Ortꢀn, Prof. Dr. D. J. Dixon
Department of Chemistry, Chemistry Research Laboratory
University of Oxford
Mansfield Road, Oxford OX1 3TA (UK)
E-mail: darren.dixon@chem.ox.ac.uk
[**] We thank the EPSRC (Leadership Fellowship to D.J.D.) and the EC
[IEF to I.O. (PIEF-GA-2010-275788)] for funding, Alison Hawkins
and David Barber of the Department of Chemistry, University of
Oxford, for X-ray analysis, and the Oxford Chemical Crystallography
Service for the use of their instrumentation.
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201309719.
Scheme 1. Proposed catalytic Mannich-type addition/cyclization reac-
tion of isocyanoacetates and ketimines. PG=protecting group.
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Chemie
Table 1: Optimization studies.
Initially, a catalyst system that
consists of silver oxide (5 mol%)
and cinchonine-derived amino-
phosphine 1a
(20 mol%)
was
examined in dichloromethane at
room temperature. A 2:1 ratio of
precatalyst to metal ion was chosen
to suppress any competing back-
ground reactions. Pleasingly, the
trans-configured imidazoline prod-
uct, (4S,5R)-4a, was obtained with
significant diastereo- and enantio-
selectivity (Table 1, entry 1; 71:29
d.r., 72% ee). A screen of metal
salts confirmed silver (rather than
gold or copper) to be the best
match for precatalyst 1a in this
reaction (entries 1–3).
Entry Precat. MLn (mol%) R1
2
T [8C] Solvent Time [h]
4
Yield[a] [%] d.r.[b] ee[c]
70 71:29 72
1
2
3
4
5
6
7
8
1a
1a
1a
1a
1a
1a
1a
1a
1a
–
Ag2O (5)
AuCl (10)
CuCl (10)
Ag2O (5)
Ag2O (5)
Ag2O (5)
Ag2O (5)
Ag2O (5)
–
CH(Ph)2 2a
CH(Ph)2 2a
CH(Ph)2 2a
CH(Ph)2 2a
CH(Ph)2 2a
RT CH2Cl2
RT CH2Cl2
RT CH2Cl2
RT TBME
RT EtOAc
48
48
48
24
24
60
60
60
4a
4a
4a
4a
4a
4a
4b
4c
4a
4a
4a
4b
20 14:86
23 43:57
2
2
44 37:63 70
68 83:17 78
78 89:11 82
89 88:12 89
CH(Ph)2 2a À20 EtOAc
tBu
CH3
2b À20 EtOAc
2c À20 EtOAc
94 91:9
74
–
9
CH(Ph)2 2a À20 EtOAc 120
CH(Ph)2 2a À20 EtOAc 120
0
–
10
11
12
Ag2O (5)
Ag2O (5)
Ag2O (5)
83 18:82
0
1b
1b
CH(Ph)2 2a À20 EtOAc
60
60
70 84:16 96
92 99:1 96
tBu
2b À20 EtOAc
A solvent survey revealed ethyl
acetate as the preferred choice in
terms of both diastereo- and enan-
tiocontrol (entries 1, 4, and 5).
Lowering the temperature of the
reaction to À208C was found to be
[a] Combined yield of both diastereomers after flash column chromatography. [b] The diastereomeric
ratio (d.r.) of the trans/cis diastereomers was determined by 1H NMR analysis of the crude reaction
mixture. [c] The enantiomeric excess (ee) of the major diastereomer was determined by HPLC analysis
on a chiral stationary phase after DPP removal. M.S.=molecular sieves, TBME= tert-butyl methyl ether.
beneficial for the enantioselectivity (entry 6; 89:11 d.r., 82%
ee). The bulky tert-butylisocyanoacetate was also reactive and
afforded the trans imidazoline (4S,5R)-4b as the major
product in better yield and enantioselectivity (entry 7; 89%,
88:12 d.r., 89% ee). In contrast, use of methyl isocyanoacetate
2c resulted in diminished enantioselectivity for the major
trans diastereomer (4S,5R)-4c (entry 8; 94%, 91:9 d.r., 74%
ee). Significantly, control experiments confirmed the impor-
tance of both the silver salt and the aminophosphine
precatalyst: In the absence of the silver salt, there was no
reaction (entry 9); without the precatalyst, enantiocontrol
was (naturally) absent, the reaction was significantly slower,
and the cis diastereomer was formed predominantly
(entry 10; 18:82 d.r.). Employing pseudoenantiomeric 1b
instead of 1a in conjunction with isocyanoacetates 2a and
2b afforded the enantiomeric products (4R,5S)-4a and
(4R,5S)-4b, respectively, as expected, but pleasingly with
enhanced enantioselectivities of 96% ee in both cases
(entries 11 and 12).
With the optimized reaction conditions established, the
scope of the reaction that is catalyzed by cinchonidine-
derived aminophosphine precatalyst 1b and Ag2O was
assessed by probing changes to both the aryl and alkyl
groups of the ketimine in reactions with bulky isocyanoace-
tates 2a and 2b (Table 2). With tert-butylisocyanoacetate
pronucleophile 2b good to excellent diastereoselectivities
and excellent enantioselectivities (93–99% ee) were observed
for DPP-protected para-substituted aryl methyl ketimines
with either electron-withdrawing or electron-donating groups
(entries 2–6). Importantly, imine 3 f, which is derived from
ethyl phenyl ketone, was also an excellent substrate and
afforded trans imidazoline 4h in high yield, good diastereo-
selectivity, and with an excellent ee of 97% (entry 7).
Table 2: Substrate scope.
Entry Ar
R2
2
4
Yield[a] [%] d.r.[b]
ee[c]
1
Ph
CH3 2a 4a
CH3 2b 4b
CH3 2b 4d
CH3 2b 4e
CH3 2b 4 f
CH3 2b 4g
70
92
87
96
78
87
85
83
96
96
80
82
96
97
98
97
95
95
84
84:16
99:1
80:20
96:4
96
96
95
93
98
99
97
97
96
98
90
96
97
97
94
96
96
96
95
2
Ph
3
4
5
6
p-NO2C6H4
p-ClC6H4
p-CH3C6H4
p-CH3OC6H4
Ph
90:10
75:25
88:12
86:14
95:5
73:27
81:19
74:26
80:20
90:10
78:22
99:1
7
Et
2b 4h
8
9
p-ClC6H4
p-CH3C6H4
p-CH3OC6H4
Ph
m-CH3OC6H4
o-CH3OC6H4
p-PhC6H4
p-BrC6H4
o-BrC6H4
o-FC6H4
p-FC6H4
CH3 2a 4i
CH3 2a 4j
CH3 2a 4k
10
11
12
13
14
15
16
17
18
19
Et
2a 4l
CH3 2a 4m
CH3 2a 4n
CH3 2a 4o
CH3 2a 4p
CH3 2a 4q
CH3 2a 4r
CH3 2a 4s
84:16
83:17
85:15
3,4-(Cl)2-C6H3 CH3 2a 4t
[a] Combined yield of both diastereomers after flash column chroma-
tography. [b] The diastereomeric ratio (d.r.) of the trans/cis diastereomers
was determined by 1H NMR analysis of the crude reaction mixture.
[c] The ee of the major diastereomer was determined by HPLC analysis
on a chiral stationary phase after DPP removal.
ketones and bear various electron-donating or electron-
withdrawing substituents in the ortho, meta, and para
positions were suitable substrates. Enantioselectivities for
the major trans diastereoisomer ranged from 94% ee with
Using diphenylmethylisocyanoacetate pronucleophile 2a
a wide range of ketimines that are derived from aryl methyl
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Table 4: Removal of the DPP protecting group.
para-bromophenyl methyl ketimine (entry 15) to 98% ee with
DPP-protected para-methoxyphenyl methyl ketimine
(entry 10). Pleasingly, DPP-protected phenyl ethyl ketimine
gave the reaction product 4l in a combined 80% yield for
both diastereomers, and with 81:19 d.r. and 90% ee for the
major trans diastereoisomer. In total, in the presence of
a combination of 1b and Ag2O, thirteen substrates proved
effective and could be converted into the corresponding trans
diastereomers with excellent enantio- and good diastereose-
lectivities.
Although a precatalyst loading of 20 mol% was found to
be convenient for assessing the substrate scope, the loading of
precatalyst 1b was reduced from 20 mol% to 10 mol%,
5 mol%, and 1 mol% at À208C to demonstrate the practic-
ability of this transformation (Table 3, entries 1–3). The
observed diastereo- and enantioselectivities were comparable
to those obtained with a precatalyst loading of 20 mol%;
however, the reaction became prohibitively slow. To shorten
the reaction time, the temperature was increased to 08C.
Entry
5
R2
Ar
R1
Yield[a] [%]
1
2
3
4
5
6
7
8
5a
5b
5d
5e
5 f
5g
5h
5i
5j
5k
5l
5m
5n
5o
5p
5q
5r
CH3
CH3
CH3
CH3
CH3
CH3
Et
CH3
CH3
CH3
Et
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
Ph
Ph
CH(Ph)2
tBu
tBu
tBu
tBu
90
89
89
95
85
63
95
60
81
83
67
85
59
90
75
70
61
87
73
p-NO2C6H4
p-ClC6H4
p-CH3C6H4
p-CH3OC6H4
Ph
p-ClC6H4
p-CH3C6H4
p-CH3OC6H4
Ph
m-CH3OC6H4
o-CH3OC6H4
p-PhC6H4
p-BrC6H4
o-BrC6H4
o-FC6H4
tBu
tBu
CH(Ph)2
CH(Ph)2
CH(Ph)2
CH(Ph)2
CH(Ph)2
CH(Ph)2
CH(Ph)2
CH(Ph)2
CH(Ph)2
CH(Ph)2
CH(Ph)2
CH(Ph)2
9
10
11
12
13
14
15
16
17
18
19
Table 3: Variation of the catalyst loading.
5s
5t
p-FC6H4
3,4-(Cl)2-C6H3
[a] Yield of isolated product after flash column chromatography.
Entry 1b
[mol%]
Ag2O
[mol%]
T
[8C]
Time Yield[a] d.r.[b] ee[c]
[h]
[%]
1
2
3
4
5
6
10
5
1
10
5
1
2.5
À20
À20
À20
0
60
120
160
24
60
60
87
78
77
89
87
58
94:6 96
93:7 96
92:8 95
89:11 95
86:14 93
87:13 94
1.25
0.25
2.5
1.25
0.25
0
0
[a] Combined yield of both diastereomers after flash column chroma-
tography. [b] The diastereomeric ratio (d.r.) of the trans/cis diastereo-
isomers was determined by 1H NMR analysis of the crude reaction
mixture. [c] The ee of the major diastereomer was determined by HPLC
analysis on a chiral stationary phase after deprotection.
Scheme 2. Chemical transformations of imidazolines.
Pleasingly, this was possible without significant detriment to
either enantio- or diastereocontrol (entries 4–6).
alkaline hydrolysis, esterification, and treatment with an
excess amount of Boc2O and DMAP [Scheme 2, Eq. (2);
Boc = tert-butoxycarbonyl, DMAP = 4-dimethylaminopyri-
dine]. The relative and absolute stereochemical configuration
of 7q was established by single-crystal X-ray analysis (for
details, see the Supporting Information).
In conclusion, we have developed an efficient and general,
diastereo- and enantioselective method for the synthesis of
highly functionalized imidazolines that possess a fully sub-
stituted stereocenter at the b-position through a Mannich-
type addition/cyclization reaction of isocyanoacetate pronu-
cleophiles and ketimines using a silver salt and cinchona-
derived aminophosphine binary catalyst system. We have also
demonstrated that chiral unprotected imidazolines and a,b-
diaminoacids can be easily obtained from the protected
imidazoline reaction products. Further studies into the
asymmetric synthesis of imidazolines with two contiguous
quaternary centers are underway, and the findings will be
reported in due course.
Aside from the high yields and stereoselectivities, an
advantage of our described method lies in the simple and
efficient synthetic manipulation of the direct Mannich
products into desirable building blocks and motifs. Protect-
ing-group-free imidazolines were obtained by the efficient
cleavage of the diphenylphosphinoyl group[13] using a 1.0m
solution of HCl in dichloromethane at room temperature
(Table 4, entries 1–19). The deprotection could be carried out
without compromising the diastereo- or enantiopurity. Impor-
tantly, the absolute configuration of the imidazolines was
confirmed by single-crystal X-ray analysis of 5u, a N-(4-
bromophenylsulfonyl) derivative of 5p (see the Supporting
Information for details). Furthermore, treatment of imidazo-
line trans-5a with an aqueous solution of potassium hydroxide
(50%) gave a,b-diaminoacid[7] 6a without a deterioration of
enantiopurity [Scheme 2, Eq. (1)]. Imidazolines trans-5q and
trans-5r were transformed into the cyclic ureas 7q and 7r by
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[5] See, for example: a) G. Lu, T. Yoshino, H. Morimoto, S.
Received: November 7, 2013
Matsunaga, M. Shibasaki, Angew. Chem. 2011, 123, 4474 –
4477; Angew. Chem. Int. Ed. 2011, 50, 4382 – 4385; b) J. Jiang,
X. Ma, S. Liu, Y. Qian, F. Lv, L. Qiu, X. Wu, W. Hu, Chem.
Commun. 2013, 49, 4238 – 4240.
Published online: February 24, 2014
Keywords: asymmetric catalysis · cooperative catalysis ·
.
imidazolines · ketimines · Mannich reaction
[6] a) X.-T. Zhou, Y.-R. Lin, L.-X. Dai, J. Sun, L.-J. Xia, M.-H. Tang,
J. Org. Chem. 1999, 64, 1331 – 1334; b) J. Aydin, A. Rydꢂn, K. J.
Szabꢃ, Tetrahedron: Asymmetry 2008, 19, 1867 – 1870; c) Z.-W.
Zhang, G. Lu, M.-M. Chen, N. Lin, Y.-B. Li, T. Hayashi, A. S. C.
Chan, Tetrahedron: Asymmetry 2010, 21, 1715 – 1721.
[7] For reports that describe the hydrolysis of the imidazoline ring to
afford the a,b-diaminoacid, see: a) J. Sang-Hun, K. Harold,
Tetrahedron Lett. 1984, 25, 399 – 402; b) R. Meyer, U. Schçllkopf,
P. Bohme, Liebigs Ann. Chem. 1977, 1183 – 1193.
[1] For reviews, see: a) A. Viso, R. Fernꢀndez de La Pradilla, A.
Garcꢁa, A. Flores, Chem. Rev. 2005, 105, 3167 – 3196; b) A. Viso,
R. F. De La Pradilla, M. Tortosa, A. Garcꢁa, A. Flores, Chem.
Rev. 2011, 111, PR1 – PR42.
[2] For reviews, see: a) R. G. Arrayꢀs, J. C. Carretero, Chem. Soc.
Rev. 2009, 38, 1940 – 1948; b) B. Karimi, D. Enders, E. Jafari,
Synthesis 2013, 45, 2769 – 2812, and references therein.
[3] a) L. Bernardi, A. S. Gothelf, R. G. Hazell, K. A. Jørgensen, J.
Org. Chem. 2003, 68, 2583 – 2591; b) T. Ooi, M. Kameda, J.-I.
Fujii, K. Maruoka, Org. Lett. 2004, 6, 2397 – 2399; c) A. Okada,
T. Shibuguchi, T. Ohshima, H. Masu, K. Yamaguchi, M.
Shibasaki, Angew. Chem. 2005, 117, 4640 – 4643; Angew. Chem.
Int. Ed. 2005, 44, 4564 – 4567; d) N. S. Chowdari, M. Ahmad, K.
Albertshofer, F. Tanaka, C. F. Barbas III, Org. Lett. 2006, 8,
2839 – 2842; e) S. Kobayashi, R. Yazaki, K. Seki, Y. Yamashita,
Angew. Chem. 2008, 120, 5695 – 5697; Angew. Chem. Int. Ed.
2008, 47, 5613 – 5615; f) J. Hernꢀndez-Toribio, R. G. Arrayꢀs,
J. C. Carretero, J. Am. Chem. Soc. 2008, 130, 16150 – 16151;
g) X.-X. Yan, Q. Peng, Q. Li, K. Zhang, J. Yao, X.-L. Hou, Y.-D.
Wu, J. Am. Chem. Soc. 2008, 130, 14362 – 14363; h) D. Shang, Y.
Liu, X. Zhou, X. Liu, X. Feng, Chem. Eur. J. 2009, 15, 3678 –
3681; i) H. Zhang, S. Syed, C. F. Barbas, Org. Lett. 2010, 12, 708 –
[8] See, for example: a) C. Betschart, L. S. Hegedus, J. Am. Chem.
Soc. 1992, 114, 5010 – 5017; b) F. Rondu, G. Le Bihan, X. Wang,
A. Lamouri, E. Touboul, G. Dive, T. Bellahsene, B. Pfeiffer, P.
Renard, B. Guardiola-Lamaitre, D. Manechez, L. Penicaud, A.
Ktorza, J. J. Godfroid, J. Med. Chem. 1997, 40, 3793 – 3803; c) Y.
Hsiao, L. S. Hegedus, J. Org. Chem. 1997, 62, 3586 – 3591.
[9] See, for example: a) J. Xu, Y. Guan, S. Yang, Y. Ng, G. Peh, C.-H.
Tan, Chem. Asian J. 2006, 1, 724 – 729; b) H. Liu, D.-M. Du, Adv.
Synth. Catal. 2010, 352, 1113 – 1118; c) H. Liu, D.-M. Du, Adv.
Synth. Catal. 2009, 351, 489 – 519.
[10] For enantioselective addition reactions of other nucleophiles or
pronucleophiles to ketimines, see: a) S. Saaby, K. Nakama, M. A.
Lie, R. G. Hazell, K. A. Jørgensen, Chem. Eur. J. 2003, 9, 6145 –
6154; b) W. Zhuang, S. Saaby, K. A. Jørgensen, Angew. Chem.
2004, 116, 4576 – 4578; Angew. Chem. Int. Ed. 2004, 43, 4476 –
4478; c) Y. Suto, M. Kanai, M. Shibasaki, J. Am. Chem. Soc.
2007, 129, 500 – 501; d) C. Baudequin, A. Zamfir, S. B. Tsogoeva,
Chem. Commun. 2008, 4637 – 4639; e) Y. Du, L.-W. Xu, Y.
Shimizu, K. Oisaki, M. Kanai, M. Shibasaki, J. Am. Chem. Soc.
2008, 130, 16146 – 16147; f) V. A. Sukach, N. M. Golovach, V. V.
Pirozhenko, E. B. Rusanov, M. V. Vovk, Tetrahedron: Asymme-
try 2008, 19, 761 – 764; g) B. Jiang, J. J. Dong, Y. G. Si, X. L.
Zhao, Z. G. Huang, M. Xu, Adv. Synth. Catal. 2008, 350, 1360 –
1366; h) L. C. Wieland, E. M. Vieira, M. L. Snapper, A. H.
Hoveyda, J. Am. Chem. Soc. 2009, 131, 570 – 576; i) N. Hara, R.
Tamura, Y. Funahashi, S. Nakamura, Org. Lett. 2011, 13, 1662 –
1665; j) N. Hara, S. Nakamura, M. Sano, R. Tamura, Y.
Funahashi, N. Shibata, Chem. Eur. J. 2012, 18, 9276 – 9280;
k) W. Yan, D. Wang, J. Feng, P. Li, D. Zhao, R. Wang, Org. Lett.
2012, 14, 2512 – 2515; l) T. Kano, S. Song, Y. Kubota, K.
Maruoka, Angew. Chem. 2012, 124, 1217 – 1220; Angew. Chem.
Int. Ed. 2012, 51, 1191 – 1194; m) M. Hayashi, M. Sano, Y.
Funahashi, S. Nakamura, Angew. Chem. 2013, 125, 5667 – 5670;
Angew. Chem. Int. Ed. 2013, 52, 5557 – 5560.
´
711; j) J. Hernꢀndez-Toribio, R. G. Array, J. C. Carretero, Chem.
Eur. J. 2010, 16, 1153 – 1157; k) G. Liang, M.-C. Tong, H. Tao, C.-
J. Wang, Adv. Synth. Catal. 2010, 352, 1851 – 1855; l) E.
Hernando, R. G. Arrayꢀs, J. C. Carretero, Chem. Commun.
2012, 48, 9622 – 9624.
[4] a) K. R. Knudsen, K. A. Jørgensen, Org. Biomol. Chem. 2005, 3,
1362 – 1364; b) G. A. Cutting, N. E. Stainforth, M. P. John, G.
Kociok-Kçhn, M. C. Willis, J. Am. Chem. Soc. 2007, 129, 10632 –
10633; c) Z. Chen, H. Morimoto, S. Matsunaga, M. Shibasaki, J.
Am. Chem. Soc. 2008, 130, 2170 – 2171; d) A. Singh, J. N.
Johnston, J. Am. Chem. Soc. 2008, 130, 5866 – 5867; e) B. Han,
Q.-P. Liu, R. Li, X. Tian, X.-F. Xiong, J.-G. Deng, Y.-C. Chen,
Chem. Eur. J. 2008, 14, 8094 – 8097; f) D. Uraguchi, K. Koshi-
moto, T. Ooi, J. Am. Chem. Soc. 2008, 130, 10878 – 10879; g) D.
Uraguchi, Y. Ueki, T. Ooi, J. Am. Chem. Soc. 2008, 130, 14088 –
14089; h) A. Puglisi, L. Raimondi, M. Benaglia, M. Bonsignore,
S. Rossi, Tetrahedron Lett. 2009, 50, 4340 – 4342; i) L. Li, M.
Ganesh, D. Seidel, J. Am. Chem. Soc. 2009, 131, 11648 – 11649;
j) D. Uraguchi, K. Koshimoto, C. Sanada, T. Ooi, Tetrahedron:
Asymmetry 2010, 21, 1189 – 1190; k) X. Liu, L. Deng, X. Jiang,
W. Yan, C. Liu, R. Wang, Org. Lett. 2010, 12, 876 – 879; l) X.
Chen, S. Dong, Z. Qiao, Y. Zhu, M. Xie, L. Lin, X. Liu, X. Feng,
Chem. Eur. J. 2011, 17, 2583 – 2586; m) A. D. Melhado, G. W.
Amarante, Z. J. Wang, M. Luparia, F. D. Toste, J. Am. Chem.
Soc. 2011, 133, 3517 – 3527; n) J. Jiang, H.-D. Xu, J.-B. Xi, B.-Y.
Ren, F.-P. Lv, X. Guo, L.-Q. Jiang, Z.-Y. Zhang, W.-H. Hu, J. Am.
Chem. Soc. 2011, 133, 8428 – 8431; o) S.-H. Shi, F.-P. Huang, P.
Zhu, Z.-W. Dong, X.-P. Hui, Org. Lett. 2012, 14, 2010 – 2013;
p) S. Nakamura, Y. Maeno, M. Ohara, A. Yamamura, Y.
Funahashi, N. Shibata, Org. Lett. 2012, 14, 2960 – 2963; q) W.-
Q. Zhang, L.-F. Cheng, J. Yu, L.-Z. Gong, Angew. Chem. 2012,
124, 4161 – 4164; Angew. Chem. Int. Ed. 2012, 51, 4085 – 4088.
[11] F. Sladojevich, A. Trabocchi, A. Guarna, D. J. Dixon, J. Am.
Chem. Soc. 2011, 133, 1710 – 1713.
[12] For a review, see: a) L. Stegbauer, F. Sladojevich, D. J. Dixon,
Chem. Sci. 2012, 3, 942 – 958; for relevant previous work from
our group on the use of metal salts, see: b) M. Li, S. Datta, D. M.
Barber, D. J. Dixon, Org. Lett. 2012, 14, 6350 – 6353; c) T. Yang,
A. Ferrali, F. Sladojevich, L. Campbell, D. J. Dixon, J. Am.
Chem. Soc. 2009, 131, 9140 – 9141; d) D. M. Barber, H. J.
Sanganee, D. J. Dixon, Org. Lett. 2012, 14, 5290 – 5293.
[13] For selected examples of the removal of the diphenylphosphi-
noyl protecting group, see: a) S. Coulton, G. A. Moore, R.
Ramage, Tetrahedron Lett. 1976, 17, 4005 – 4008; b) A. Zwier-
´
zak, I. Podstawezynska, Angew. Chem. 1977, 89, 737 – 738;
Angew. Chem. Int. Ed. Engl. 1977, 16, 702 – 704.
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