Catalytic asymmetric 1,2-addition of α-isothiocyanato phosphonates: Synthesis of chiral β-hydroxy- or β-amino-substituted α-amino phosphonic acid derivatives

Article abstract of DOI:10.1002/anie.201308514

α-Amino phosphonic acid derivatives are considered to be the most important structural analogues of α-amino acids and have a very wide range of applications. However, approaches for the catalytic asymmetric synthesis of such useful compounds are very limited. In this work, simple, efficient, and versatile organocatalytic asymmetric 1,2-addition reactions of α-isothiocyanato phosphonate were developed. Through these processes, derivatives of β-hydroxy-α-amino phosphonic acid and α,β-diamino phosphonic acid, as well as highly functionalized phosphonate-substituted spirooxindole, can be efficiently constructed (up to 99 % yield, d.r. >20:1, and >99 % ee). This novel method provides a new route for the enantioselective functionalization of α-phosphonic acid derivatives. Correct chirality critical: Organocatalytic asymmetric Adol-type and Mannich-type reactions of α-isothiocyanato phosphonate have been realized. Michael addition was also applicable under the same catalytic conditions. This versatile approach provides a new route for the synthesis of diverse highly optically active functionalized α-amino phosphonic acid derivatives. Copyright

Full text of DOI:10.1002/anie.201308514

.
Angewandte
Communications
DOI: 10.1002/anie.201308514
Asymmetric Synthesis
Catalytic Asymmetric 1,2-Addition of a-Isothiocyanato Phosphonates:
Synthesis of Chiral b-Hydroxy- or b-Amino-Substituted a-Amino
Phosphonic Acid Derivatives**
Yi-Ming Cao, Fang-Fang Shen, Fu-Ting Zhang, Jin-Long Zhang, and Rui Wang*
Abstract: a-Amino phosphonic acid derivatives are consid-
ered to be the most important structural analogues of a-amino
acids and have a very wide range of applications. However,
approaches for the catalytic asymmetric synthesis of such
useful compounds are very limited. In this work, simple,
efficient, and versatile organocatalytic asymmetric 1,2-addition
reactions of a-isothiocyanato phosphonate were developed.
Through these processes, derivatives of b-hydroxy-a-amino
phosphonic acid and a,b-diamino phosphonic acid, as well as
highly functionalized phosphonate-substituted spirooxindole,
can be efficiently constructed (up to 99% yield, d.r. > 20:1, and
> 99% ee). This novel method provides a new route for the
enantioselective functionalization of a-phosphonic acid deriv-
atives.
D
erivatives of a-amino phosphonic acid are considered to
be the most important structural analogues of a-amino acids
and they also mimic the tetrahedral intermediates of peptide
hydrolysis. Naturally occurring[1] and synthetic compounds
incorporating such units are widely used in the fields of
medicinal chemistry,[2] agriculture,[2c] metallurgy[3] and asym-
metric catalysis.[4] Because of their practical importance, such
organophophoric molecules have drawn tremendous interest
from synthetic and medicinal chemists.[5] Since it is well
known that the chirality of the a-carbon center is critical for
the properties of the a-amino phosphonic acid derivatives,
enantiomerically controlled synthesis is essential, and
a number of elegant catalytic asymmetric syntheses have
reported.[6] Several approaches were developed in these
reports, and these can be divided into five main strategies
(Scheme 1a: strategies A,[7] B,[8] C,[9] D,[10] and E[11]).
Scheme 1. Reported strategies (a) and the strategy presented in this
work (b) for the catalytic asymmetric synthesis of a-Amino phosphonic
acid derivatives.EWG=electron-withdrawing group, PG=protecting
group, FG=precursor of the amino group.
acid derivatives can be synthesized through several simple
À
and atom-economic catalytic asymmetric C C bond forma-
tion processes (such as Aldol, Mannich, and Michael addi-
tions). However, such an approach is in fact very challenging,
mostly because of 1) the poor stability of a carbon anion a to
the phosphonates and 2) the large steric hindrance caused by
the bulky tetrahedral phosphonate group (Scheme 1b). To
date, there have only been a few reports of the application of
this strategy and all of them use either relatively strong base
(such as LDA and KOtBu) for the deprotonation[10e–i] or
Among the above-mentioned routes, nucleophilic addi-
tion of the anionic a-amino phosphonic acid equivalents
(strategy D) seems to be a very convenient and versatile
method because by employing different kinds of electro-
philes, a variety of functionalized chiral a-amino phosphonic
[*] Y.-M. Cao, F.-F. Shen, F.-T. Zhang, J.-L. Zhang, Prof. Dr. R. Wang
Key Laboratory of Preclinical Study for New Drugs of Gansu
Province, School of Basic Medical Sciences, Lanzhou University
Lanzhou, 730000 (China)
incorporation of
a strong electron-withdrawing group
(-NO2)[10a–d] to activate the a-carbon. In this context,
a simple and efficient method for the synthesis of a-amino
phosphonic acid derivatives is still very much needed.
E-mail: wangrui@lzu.edu.cn
[**] We are grateful for grants from the National Natural Science
Foundation of China (Nos. 91213302, 20932003 and 21272102), the
Key National S&T Program “Major New Drug Development” of the
Ministry of Science and Technology of China (2012ZX09504001-
003) and the Program for Changjiang Scholars and Innovative
Research Team in University (PCSIRT: IRT1137).
Catalytic asymmetric transformations employing a-iso-
thiocyanato compounds have recently been found to be very
useful processes for the enantioselective construction of
a variety of useful chiral compounds.[12] As part of our
ongoing interest in transformations involving a-isothiocya-
nato compounds[12i,j,n,o,q,r] and the asymmetric synthesis of
amino phosphonic acid derivatives,[13] we focused our atten-
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201308514.
1862
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2014, 53, 1862 –1866

Angewandte
Chemie
Table 1: Optimization of the reaction.[a]
tion on the development of a novel synthetic method
involving the use of isothiocyanato compounds for the
construction of functionalized chiral a-amino phosphonic
acid derivatives. The poor nucleophilicity of anionic a-amino
phosphonic acid equivalents results in a small equilibrium
constant for their addition to electrophiles. We envisaged that
the a-isothiocyanato phosphonates[14] would be perfect reac-
tants because the anion generated in the addition step can
subsequently be quenched by the isothiocyanate moiety, thus
pushing the reaction forward (Scheme 1b). Through the
catalytic asymmetric Aldol and Mannich-type addition of a-
phosphonates, optically active b-hydroxy-a-amino (phospho-
serine and phosphothreonine analogues) and a,b-diamino
phosphonic acid derivatives can be obtained in an efficient
manner. These important phosphonic acid derivatives possess
biologically significant properties but methods for their
catalytic chiral synthesis are very limited.[10d,e,15]
On the basis of our recent studies on organocatalytic
enantioselective reactions involving a-isothiocyanato com-
pounds, we surmised that a bifunctional thiourea catalyst[16]
would be suitable for catalyzing the 1,2-addition of a-
isothiocyanato phosphonates in a double-activation mode.
The initial investigation began with the reaction of the diethyl
a-isothiocyanato phosphonate 1a with benzaldehyde (2a) in
toluene in the presence of the quinidine-derived thiourea L1
at a 20 mol% loading (Table 1). After 48 h at 508C, the
expected product 3 was obtained in 58% yield, with d.r. 9:1
and 68% ee (Table 1, entry 1). To enhance the reactivity of
the isothiocyanates, the diphenyl phosphonate 1b was then
tested, and to our delight, it gave the adduct in an increased
yield at 308C (83%; Table 1, entry 2). Next, several tertiary
amine–thioureas with different types of structural scaffold,
namely cinchonine, cyclohexanediamine, and binaphthyl-
amine, were screened (Table 1, entries 3–5). However, the
enatioselectivity of the reaction was still moderate. To address
the need for enhanced enantioselectivity, we then screened
squaramide-based H-bond-donor catalysts[17] with an
increased distance between the donor hydrogens, which
might be able to constrain the substrates in a well-defined
orientation for the asymmetric induction. To our delight, the
quinine-derived squaramide-based H-bonding catalyst L6
gave the product with excellent stereocontrol (96% ee, d.r.
> 20:1; Table 1, entry 7). Moreover, the reactivity was further
enhanced since the adduct was obtained in 92% yield in only
half of the time used before. Screening of solvents revealed
that Et2O was the most suitable for this process (95% yield,
d.r. > 20:1 and 98% ee; Table 1, entry 11). Notably, the ent
product could also be accessed with the same excellent results
when L6ꢀ was used (Table 1, entry 12).
Entry Cat.
R
Solvent T [8C] t [h] Yield [%][b] d.r.[c]
ee [%][d]
1
2
3
4
5
6
7
8
L1
L1
L2
L3
L4
L5
L6
L6
L6
L6
L6
Et Tol
Ph Tol
Ph Tol
Ph Tol
Ph Tol
Ph Tol
Ph Tol
Ph CH2Cl2 30
Ph MeCN 30
Ph THF
Ph Et2O
50
30
30
30
30
30
30
48
48
48
48
48
48
24
36
96
72
16
16
58
83
79
78
trace
85
92
96
89
92
95
94
9:1 68
9:1 56
13:1 60
9:1 69
–
–
>20:1 73
>20:1 96
>20:1 98
16:1 97
9
10
11
12
30
30
30
>20:1 97
>20:1 98
>20:1 95
L6’ Ph Et2O
[a] Unless otherwise specified, the reaction was performed on
a 0.1 mmol scale with 1 (1.0 equiv), 2a (2.0 equiv), and catalyst L
(20 mol%) in 1 mL solvent. [b] Yield of isolated product as a mixture of
diastereoisomers. [c] Determined by 1H and 31P NMR analysis.
[d] Determined by HPLC analysis on a chiral stationary phase.
ated and gave the corresponding adducts with excellent yield
and steroecontrol (Table 2, entry 5 and entry 7). The ortho-
methyl-substituted substrate, however, resulted in only
a moderate yield (66% yield, Table 2, entry 13). Sterically
hindered 1-naphthaldehyde was also applicable in the process
and gave the product with 86% yield, d.r. > 20:1, and 93% ee
(Table 2, entry 16). Various aldehydes containing heteroar-
omatic rings, as well as cinnamaldehyde, were also suitable
and afforded the desired compounds with excellent results in
terms of yield and stereocontrol (Table 2, entries 17–19).
Encouraged by the successful development of this Aldol
reaction with diphenyl a-isothiocyanato phosphonate, we
then attempted to extend the 1,2-addition to Mannich-type
reactions for the enantioselective synthesis of a,b-diamino
phosphonic acid derivatives. The model reaction was per-
formed between 1b and the N-Ts protected imines 4
(Table 3). To our delight, the same conditions were suitable
for the new process and no further optimization was needed
(Table 3, entry 1). Imines with both electron-donating and
electron-withdrawing substituents at different positions on
With the optimal reaction conditions established, the
substrate scope of the catalytic asymmetric Aldol-type
reaction was investigated by using a series of aldehydes
(Table 2). Various benzaldehyde derivatives with either
electron-withdrawing or electron-donating groups at the
para or meta positions on the aromatic ring reacted smoothly,
and the corresponding products were obtained with excellent
chemical yield, diastereoselectivity, and enantioselectivity
(Table 2, entries 2–4, 6, 8–12, 14, 15). The sterically hindered
ortho-chloro/bromo-substituted substrates were also toler-
Angew. Chem. Int. Ed. 2014, 53, 1862 –1866
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
1863

.
Angewandte
Communications
Table 2: Scope of the catalytic asymmetric synthesis of b-hydroxy-a-
Table 3: Scope of the catalytic asymmetric synthesis of a,b-diamino
amino phosphonic acid derivatives.[a]
phosphonic acid derivatives.[a]
Product, yield [%][b]
d.r.[c]
ee [%][d]
E ntry
R
yield [%][b]
d.r.[c]
ee [%][d]
Entry
R
1
2
3
4
5
6
7
Ph
5ba, 95
5bb, 99
5bc, 94
5bd, 98
5be, 96
5bf, 92
5bg, 92
5bh, 80
5bi, 91
12:1
10:1
9:1
11:1
8:1
10:1
10:1
6:1
>99
>99
97
1
2
3
4
5
6
7
8
Ph
4-F-C6H4
3ba, 95
3bb, 99
3bc, 87
3bd, 81
3be, 95
3bf, 99
3bg, 93
3bh, 89
3bi, 96
3bj, 85
3bk, 94
3bl, 97
3bm, 66
3bn, 97
>20:1
>20:1
>20:1
>20:1
16:1
19:1
20:1
17:1
20:1
98
97
95
95
90
95
91
96
>99
92
4-F-C6H4
4-Cl-C6H4
2-Cl-C6H4
4-Me-C6H4
3-Me-C6H4
2-Me-C6H4
4-MeO-C6H4
2-thienyl
4-Cl-C6H4
3-Cl-C6H4
2-Cl-C6H4
3-Br-C6H4
2-Br-C6H4
4-NO2-C6H4
3-NO2-C6H4
4-CF3-C6H4
4-Me-C6H4
3-Me-C6H4
2-Me-C6H4
4-MeO-C6H4
96
>99
>99
92
>99
97
8[e]
9
10:1
9
10
11
12
13
14
20:1
[a] Unless otherwise specified, the reaction was performed on
>20:1
>20:1
>20:1
>20:1
98
96
95
98
a 0.1 mmol scale with 1b (1.0 equiv), 4 (1.2 equiv), and catalyst L6
(20 mol%) in 1 mL Et2O at 308C for 48 h. [b] Yield of isolated product as
a mixture of diastereoisomers. [c] Determined by 1H and 31P NMR
analysis. [d] Determined by HPLC analysis on a chiral stationary phase.
[e] The reaction time is 72 h. Ts=toluene-4-sulfonyl.
15
3bo, 91
>20:1
98
16
17
18
19
1-naphthyl
2-thienyl
2-furyl
3 bp, 86
3bq, 91
3br, 96
3bs, 97
>20:1
>20:1
>20:1
>20:1
93
96
87
96
cinnamyl
[a] Unless otherwise specified, the reaction was performed on
a 0.1 mmol scale with 1b (1.0 equiv), 2 (2.0 equiv), and catalyst L6
(20 mol%) in 1 mL Et2O at 308C for 48 h. [b] Yield of isolated product as
a mixture of diastereoisomers. [c] Determined by 1H and 31P NMR
analysis. [d] Determined by HPLC analysis on a chiral stationary phase.
the phenyl ring gave the corresponding products with good
results in terms of yield and stereocontrol (Table 3, entries 1–
8). A substrate containing a heteroaromatic ring was also
tolerated (Table 3, entry 9). Generally, the diastereoselectiv-
ity of the Mannich reaction was lower than that of the Aldol
reaction, while the ee values for the Mannich adducts were
slightly higher. The absolute configuration of product 3bb
was unambiguously determined by X-ray crystallography.[18]
On the basis of the experimental results, we have proposed
a model to explain the stereochemistry of the Aldol/cycliza-
tion reaction sequence (Scheme 2). Attack at the Si face of
the aldehyde leads to the formation of the major (4R,5R)
product.
Scheme 2. Proposed transition states.
Scheme 3. Synthesis of chiral phosphonate-substituted spirooxindole
through Michael-cyclization of a-isothiocyanato phosphonate with an
activated olefin.
To further expand the scope of our method, we also
investigated the performance of a-isothiocyanato phospho-
nate in the catalytic asymmetric 1,4-addition process. The
methyleneindolinone
6 was employed as the Michael
acceptor. The reaction proceeded smoothly under the de-
scribed conditions and afforded the phosphonate-substituted
spirooxindole with 80% yield, d.r. > 20:1, and 98% ee
(Scheme 3).[18]
In summary, an organocatalyzed enantioselective 1,2-
addition reaction of a-isothiocyanato phosphonate has been
successfully developed. This simple and efficient process
provides a novel approach for the asymmetric synthesis of
both the b-hydroxy-a-amino (up to 99% yield, d.r > 20:1. and
> 99% ee) and a,b-diamino (up to 99% yield, d.r. 12:1 and
> 99% ee) phosphonic acid derivatives. Moreover, Michael
addition of the a-isothiocyanato phosphonate was also viable
under the established conditions. The versatile method
presented herein offers an excellent starting point for the
synthesis of diverse functionalized a-amino phosphonic acid
derivatives. Further studies on expanding the application of
this strategy and modifying peptides by using the obtained
compounds are in progress.
1864
www.angewandte.org
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2014, 53, 1862 –1866

Angewandte
Chemie
Chem. Int. Ed. 2006, 45, 1615 – 1617; d) H. Kiyohara, R.
Received: September 30, 2013
Revised: October 30, 2013
Published online: January 13, 2014
Matsubara, S. Kobayashi, Org. Lett. 2006, 8, 5333 – 5335; e) S.
Kobayashi, H. Kiyohara, Y. Nakamura, R. Matsubara, J. Am.
Chem. Soc. 2004, 126, 6558 – 6559.
[10] Selected examples of catalytic asymmetric synthesis: a) K. Bera,
I. N. N. Namboothiri, Adv. Synth. Catal. 2013, 355, 1265 – 1270;
b) C. B. Tripathi, S. Kayal, S. Mukherjee, Org. Lett. 2012, 14,
3296 – 3299; c) K. Bera, I. N. N. Namboothiri, Org. Lett. 2012, 14,
980 – 983; d) J. C. Wilt, M. Pink, J. N. Johnston, Chem. Commun.
2008, 4177 – 4179; e) R. D. Momo, F. Fini, L. Bernardi, A. Ricci,
Adv. Synth. Catal. 2009, 351, 2283 – 2287; f) Z. M. Jꢂszay, G.
Keywords: a-amino phosphonic acids · asymmetric synthesis ·
a-isothiocyanato compounds · organocatalysis ·
synthetic methods
.
[1] Selected examples: a) M. Yamato, T. Koguchi, R. Okachi, K.
Yamada, K. Nakayama, H. Kase, J. Antibiot. 1986, 39, 44 – 52;
b) I. Ntai, M. L. Manier, D. L. Hachey, B. O. Bachmann, Org.
Lett. 2005, 7, 2763 – 2765.
[2] Selected examples: a) J. G. Allen, F. R. Atherton, M. J. Hall,
C. H. Hassall, S. W. Holmes, R. W. Lambert, L. J. Nisbet, P. S.
Ringrose, Nature 1978, 272, 56 – 58; b) R. F. Pratt, Science 1989,
246, 917 – 919; c) I. A. Natchev, Liebigs Ann. Chem. 1988, 861 –
867.
˝
Nꢁmeth, T. S. Pham, I. Petnehꢂzy, A. Grꢃn, L. Toke, Tetrahe-
dron: Asymmetry 2005, 16, 3837 – 3840; g) I. C. Baldwin, J. M. J.
Williams, Tetrahedron: Asymmetry 1995, 6, 679 – 682; h) Y.
Yamashita, X.-X. Guo, R. Takashita, S. Kobayashi, J. Am.
Chem. Soc. 2010, 132, 3262 – 3263; i) R. Kuwano, R. Nishio, Y.
Ito, Org. Lett. 1999, 1, 837 – 839.
[11] Selected examples of catalytic asymmetric synthesis: a) N. S.
Goulioukina, I. A. Shergold, G. N. Bondarenko, M. M. Ilyin,
V. A. Davankov, I. P. Beletskaya, Adv. Synth. Catal. 2012, 354,
2727 – 2733; b) N. S. Goulioukina, G. N. Bondarenko, S. E.
Lyubimov, V. A. Davankov, K. N. Gavrilov, I. P. Beletskaya,
Adv. Synth. Catal. 2008, 350, 482 – 492; c) M. Qiu, X.-P. Hu, J.-D.
Huang, D.-Y. Wang, J. Deng, S.-B. Yu, Z.-C. Duan, Z. Zheng,
Adv. Synth. Catal. 2008, 350, 2683 – 2689; d) D.-Y. Wang, J.-D.
Huang, X.-P. Hu, J. Deng, S.-B. Yu, Z.-C. Duan, Z. Zheng, J. Org.
Chem. 2008, 73, 2011 – 2014; e) I. D. Gridnev, M. Yasutake, T.
Imamoto, I. P. Beletskaya, Proc. Natl. Acad. Sci. USA 2004, 101,
5385 – 5390; f) I. Grassert, U. Schmidt, S. Ziegler, C. Fischer, G.
Oehme, Tetrahedron: Asymmetry 1998, 9, 4193 – 4202; g) U.
Schçllkopf, I. Hoppe, A. Thiele, Liebigs Ann. Chem. 1985, 555 –
559.
´
[3] V. Jagodic, M. J. Herak, J. Inorg. Nucl. Chem. 1970, 32, 1323 –
1332.
[4] Selected examples: Q. Tao, G. Tang, K. Lin, Y.-F. Zhao, Chirality
2008, 20, 833 – 838.
[5] Selected recent reviews: a) M. OrdꢀÇez, F. J. Sayago, C.
Cativiela, Tetrahedron 2012, 68, 6369 – 6412; b) M. OrdꢀÇez,
H. Rojas-Cabrera, C. Cativiela, Tetrahedron 2009, 65, 17 – 49.
[6] Selected recent reviews: a) Ł. Albrecht, A. Albrecht, H.
Krawczyk, K. A. Jørgensen, Chem. Eur. J. 2010, 16, 28 – 48;
b) P. Merino, E. Marquꢁs-Lꢀpez, R. P. Herrera, Adv. Synth.
Catal. 2008, 350, 1195 – 1208; c) J.-A. Ma, Chem. Soc. Rev. 2006,
35, 630 – 636; d) H. Grçger, B. Hammer, Chem. Eur. J. 2000, 6,
943 – 948.
[7] Selected examples of catalytic asymmetric synthesis: a) H. Xie,
A. Song, X. Zhang, X. Chen, H. Li, C. Sheng, W. Wang, Chem.
Commun. 2013, 49, 928 – 930; b) G. K. Ingle, Y. Liang, M. G.
Mormino, G. Li, F. R. Fronczek, J. C. Antilla, Org. Lett. 2011, 13,
2054 – 2057; c) M. Ohara, S. Nakamura, N. Shibata, Adv. Synth.
Catal. 2011, 353, 3285 – 3289; d) S. Nakamura, M. Hayashi, Y.
Hiramatsu, N. Shibata, Y. Funahashi, T. Toru, J. Am. Chem. Soc.
2009, 131, 18240 – 18241; e) X. Fu, W.-T. Loh, Y. Zhang, T. Chen,
T. Ma, H. Liu, J. Wang, C.-H. Tan, Angew. Chem. 2009, 121,
7523 – 7526; Angew. Chem. Int. Ed. 2009, 48, 7387 – 7390; f) X.
Cheng, R. Goddard, G. Buth, B, List, Angew. Chem. 2008, 120,
5157 – 5159; Angew. Chem. Int. Ed. 2008, 47, 5079 – 5081; g) F.
Fini, G. Micheletti, L. Bernardi, D. Pettersen, M. Fochi, A. Ricci,
Chem. Commun. 2008, 4345 – 4347; h) S. Nakamura, H. Naka-
shima, A. Yamamura, N. Shibata, T. Torua, Adv. Synth. Catal.
2008, 350, 1209 – 1212; i) B. Saito, H. Egami, T. Katsuki, J. Am.
Chem. Soc. 2007, 129, 1978 – 1986; j) T. Akiyama, H. Morita, J.
Itoh, K. Fuchibe, Org. Lett. 2005, 7, 2583 – 2585; k) D. Pettersen,
M. Marcolini, L. Bernardi, F. Fini, R. P. Herrera, V. Sgarzani, A.
Ricci, J. Org. Chem. 2006, 71, 6269 – 6272; l) G. D. Joly, E. N.
Jacobsen, J. Am. Chem. Soc. 2004, 126, 4102 – 4103; m) I.
Schlemminger, Y. Saida, H. Grçger, W. Maison, N. Durot, H.
Sasai, M. Shibasaki, J. Martens, J. Org. Chem. 2000, 65, 4818 –
4825; n) H. Grçger, Y. Saida, H. Sasai, K. Yamaguchi, J. Martens,
M. Shibasaki, J. Am. Chem. Soc. 1998, 120, 3089 – 3103; o) H.
Sasai, S. Arai, Y. Tahara, M. Shibasaki, J. Org. Chem. 1995, 60,
6656 – 6657.
[12] Selected examples: a) G. Lu, T. Yoshino, H. Morimoto, S.
Matsunaga, M. Shibasaki, Angew. Chem. 2011, 123, 4474 – 4477;
Angew. Chem. Int. Ed. 2011, 50, 4382 – 4385; b) T. Yoshino, H.
Morimoto, G. Lu, S. Matsunaga, M. Shibasaki, J. Am. Chem. Soc.
2009, 131, 17082 – 17083; c) L. Li, M. Ganesh, D. Seidel, J. Am.
Chem. Soc. 2009, 131, 11648 – 11649; d) L. Li, E. G. Klauber, D.
Seidel, J. Am. Chem. Soc. 2008, 130, 12248 – 12249; e) G. A.
Cutting, N. E. Stainforth, M. P. John, G. Kociok-Kçhn, M. C.
Willis, J. Am. Chem. Soc. 2007, 129, 10632 – 10633; f) M. C.
Willis, G. A. Cutting, V. J.-D. Piccio, M. J. Durbin, M. P. John,
Angew. Chem. 2005, 117, 1567 – 1569; Angew. Chem. Int. Ed.
2005, 44, 1543 – 1545; g) S. Kato, T. Yoshino, M. Shibasaki, M.
Kanai, S. Matsunaga, Angew. Chem. 2012, 124, 7113 – 7116;
Angew. Chem. Int. Ed. 2012, 51, 7007 – 7010; h) W.-B. Chen, Z.-J.
Wu, J. Hu, L.-F. Cun, X.-M. Zhang, W.-C. Yuan, Org. Lett. 2011,
13, 2472 – 2475; i) X.-X. Jiang, Y.-M. Cao, Y.-Q. Wang, L.-P. Liu,
F.-F. Shen, R. Wang, J. Am. Chem. Soc. 2010, 132, 15328 – 15333;
j) Y.-M. Cao, F.-F. Shen, F.-T. Zhang, R. Wang, Chem. Eur. J.
2013, 19, 1184 – 1188; k) H. Wu, L.-L. Zhang, Z.-Q. Tian, Y.-D.
Huang, Y.-M. Wang, Chem. Eur. J. 2013, 19, 1747 – 1753; l) W.-Y.
Han, S.-W. Li, Z.-J. Wu, X.-M. Zhang, W.-C. Yuan, Chem. Eur. J.
2013, 19, 5551 – 5556; m) B. Tan, X. Zeng, W. W. Y. Leong, Z.
Shi, C. F. Barbas III, G.-F. Zhong, Chem. Eur. J. 2012, 18, 63 – 67;
n) Y.-M. Cao, X.-X. Jiang, L.-P. Liu, F.-F. Shen, F.-T. Zhang, R.
Wang, Angew. Chem. 2011, 123, 9290 – 9293; Angew. Chem. Int.
Ed. 2011, 50, 9124 – 9127; o) Y.-M. Cao, F.-T. Zhang, F.-F. Shen,
R. Wang, Chem. Eur. J. 2013, 19, 9476 – 9480; p) X. Chen, Y.
Zhu, Z. Qiao, M. Xie, L. Lin, X. Liu, X. Feng, Chem. Eur. J. 2010,
16, 10124 – 10129; q) X. Jiang, G. Zhang, D. Fu, Y. Cao, F. Shen,
R. Wang, Org. Lett. 2010, 12, 1544 – 1547; r) L. Liu, Y. Zhong, P.
Zhang, X. Jiang, R. Wang, J. Org. Chem. 2012, 77, 10228 – 10234;
s) M.-X. Zhao, H. Zhou, W.-H. Tang, W.-S. Qu, M. Shi, Adv.
Synth. Catal. 2013, 355, 1277 – 1283; t) J. Guang, C.-G. Zhao,
Tetrahedron: Asymmetry 2011, 22, 1205 – 1211.
[8] a) L. Bernardi, W. Zhuang, K. A. Jørgensen, J. Am. Chem. Soc.
2005, 127, 5772 – 5773; b) S. M. Kim, H. R. Kim, D. Y. Kim, Org.
Lett. 2005, 7, 2309 – 2311.
[9] Selected examples of catalytic asymmetric synthesis: a) J.
Vicario, J. M. Ezpeleta, F. Palacios, Adv. Synth. Catal. 2012,
354, 2641 – 2647; b) R. Dodda, C.-G. Zhao, Tetrahedron Lett.
2007, 48, 4339 – 4342; c) H. Kiyohara, Y. Nakamura, R. Matsu-
bara, S. Kobayashi, Angew. Chem. 2006, 118, 1645 – 1647; Angew.
Angew. Chem. Int. Ed. 2014, 53, 1862 –1866
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
1865

.
Angewandte
Communications
[13] Reviews: a) D. Zhao, R. Wang, Chem. Soc. Rev. 2012, 41, 2095 –
2108; For selected example, see: b) D. Zhao, Y. Wang, L. Mao,
R. Wang, Chem. Eur. J. 2009, 15, 10983 – 10987; c) D. Yang, D.
Zhao, L. Mao, L. Wang, R. Wang, J. Org. Chem. 2011, 76, 6426 –
6431.
[14] a) R. Błaszczyk, T. Gajda, Tetrahedron Lett. 2007, 48, 5859 –
5863; b) K. Błaz˙ewska, D. Sikor, T. Gajda, Tetrahedron Lett.
2003, 44, 4747 – 4750; c) During the revision of the manuscript,
Yuan and co-workers reported an enantioselective Aldol
reaction of a-isothiocyanato phosphonates, see: W.-Y. Han, J.-
Q. Zhao, Z.-J. Wu, X.-M. Zhang, W.-C. Yuan, J. Org. Chem.
2013, 78, 10541 – 10547.
Tetrahedron Lett. 1995, 36, 5769 – 5772; c) A. Togni, S. D. Pastor,
Tetrahedron Lett. 1989, 30, 1071 – 1072; d) M. Sawamura, Y. Ito,
T. Hayashi, Tetrahedron Lett. 1989, 30, 2247 – 2250.
[16] Selected reviews on bifunctional thiourea catalysis: a) A. G.
Doyle, E. N. Jacobsen, Chem. Rev. 2007, 107, 5713 – 5743; b) S. J.
Connon, Chem. Eur. J. 2006, 12, 5418 – 5427; c) M. S. Taylor,
E. N. Jacobsen, Angew. Chem. 2006, 118, 1550 – 1573; Angew.
Chem. Int. Ed. 2006, 45, 1520 – 1543; d) Y. Takemoto, Org.
Biomol. Chem. 2005, 3, 4299 – 4306.
[17] a) W. Yang, D.-M. Du, Org. Lett. 2010, 12, 5450 – 5453; b) J. P.
Malerich, K. Hagihara, V. H. Rawal, J. Am. Chem. Soc. 2008,
130, 14416 – 14417.
[15] Selected examples: a) C.-Y. Zhou, J.-C. Wang, J. Wei, Z.-J. Xu, Z.
Guo, K.-H. Low, C.-M. Che, Angew. Chem. 2012, 124, 11538 –
11542; Angew. Chem. Int. Ed. 2012, 51, 11376 – 11380; b) M.
Kitamura, M. Tokunaga, T. Pham, W. D. Lubell, R. Noyori,
[18] CCDC 936073 and CCDC 963539 contain the supplementary
crystallographic data for this paper. These data can be obtained
free of charge from The Cambridge Crystallographic Data
Centre via www.ccdc.cam.ac.uk/data_request/cif.
1866
www.angewandte.org
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2014, 53, 1862 –1866