Enantioselective organocatalytic conjugate addition of fluorocarbon nucleophiles to α,β-unsaturated aldehydes

Article abstract of DOI:10.1002/chem.200901260

Highly chemo- and enantioselective organocatalytic conjugate additions of fluorocarbon nucleophiles to a,b-unsaturated aldehydes and the construction of a quaternary carbon stereocenter bearing a fluorine atom with high enantioselectivity was reported. Af

Full text of DOI:10.1002/chem.200901260

COMMUNICATION
DOI: 10.1002/chem.200901260
Enantioselective Organocatalytic Conjugate Addition of Fluorocarbon
Nucleophiles to a,b-Unsaturated ACHUTNGRENNUG ldehydes
Farman Ullah,[a] Gui-Ling Zhao,[a] Luca Deiana,[a] Mingzhao Zhu,[a] Pawel Dziedzic,[a]
Ismail Ibrahem,[a] Peter Hammar,[c] Junliang Sun,[b] and Armando Cꢀrdova*[a]
There is a great need, in both industry and academia, for
enantiopure fluorine-containing organic molecules because
of their unique pharmacological properties.[1] Thus, mono-
fluorinated compounds are commonly employed in medici-
nal chemistry to improve metabolic stability, bioavailability,
and drug-protein interactions of biologically active com-
pounds.[2] For example, the exchange of a metabolically
active hydrogen atom to a metabolically active fluorine
atom increases the in vivo lifetime of pharmaceuticals. In
this context, enantioselective monofluoromethylation is an
important area in pharmaceutical chemistry, material sci-
ence, and in health care.[1,3]
In 2000, Hinterman and Togni reported the first example
of an enantioselective catalytic electrophilic a-fluorination
reaction.[4] Based on the vast number of potential applica-
tions, the development of catalytic regio- and enantioselec-
tive fluorination methods has become a subject of intense
research during the last decade.[5] Both transition-metal
complexes and organocatalysts have been employed as cata-
lysts for the asymmetric fluorination of organic compounds
using Selectfluor or N-fluorobenzenesulfonimide (NFSI) as
electrophilic fluorinating agents.[5–7] In comparison, the em-
ployment of fluorocarbon nucleophiles in asymmetric addi-
tion reactions is less explored.[8] Thus, there is an important
need for the development of more catalytic asymmetric
methods. For example, 1-fluoro-bis(phenylsulfonyl)methane
(FBSM) has been exploited, by the group of Shibata, as a
synthetic equivalent of a monofluoromethide species in pal-
ladium-catalyzed asymmetric allylation reactions and Man-
nich reactions.[9] Prakash, Olah, and co-workers have em-
ployed FBSM as the nucleophile in non-asymmetric Mitsu-
nobu, Michael addition, and nucleophilic substitution reac-
tions.[10] Moreover, Hu and co-workers reported the use of
FBSM in non-asymmetric nucleophilic epoxide openings.[11]
Recently, Shibata and co-workers reported the enantioselec-
tive addition of FBSM to chalcone derivatives using cincho-
na-derived ammonium salts as catalysts.[8a] Prakash and
Olah almost simultaneously reported the addition of 1-
fluoro-1-nitro(phenylsulfonyl)methane (FNSM) to chalcones
employing cinchona-based bifunctional chiral catalysts.[8b]
Aminocatalysis has proven to be a powerful procedure,[12]
within the field of organocatalysis, for the enantioselective
transformations of carbonyl compounds. In this context, imi-
nium activation[12c] has been successfully demonstrated in
Michael-type b-functionalizations with carbon nucleo-
philes.[13–14] Based on our previous research experience and
the importance of developing asymmetric addition reactions
with fluorocarbon nucleophiles, we envisioned a direct route
to synthetically useful, optically active monofluoro contain-
ing aldehydes 3 by amine-catalyzed stereoselective reactions
between nucleophiles, such as 2 and enals 1 (Scheme 1).
[a] Dr. F. Ullah, Dr. G.-L. Zhao, L. Deiana, Dr. M. Zhu, P. Dziedzic,
Dr. I. Ibrahem, Prof. Dr. A. Cꢀrdova
Department of Organic Chemistry, The Arrhenius Laboratory
Stockholm University, 106 91 Stockholm (Sweden)
Fax : (+46)8-154908
E-mail: acordova@organ.su.se
acordova1a@netscape.net
[b] Prof. Dr. J. Sun
Department of Structural Chemistry, The Arrhenius Laboratory
Stockholm University, 106 91 Stockholm (Sweden)
[c] P. Hammar
Department of Theoretical Chemistry
The Royal Institute of Technology, ALBANOVA
SE-106 91 Stockholm (Sweden)
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.200901260.
Scheme 1. Amine-catalyzed addition of fluorocarbon nucleophiles to
enals.
Chem. Eur. J. 2009, 15, 10013 – 10017
ꢁ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
10013

However, there are inherent difficulties in the addition of 1-
fluoro(phenylsulfonyl)methane compounds to enals due to
the reversibility of the nucleophilic attack and competition
between 1,2- and 1,4-addition (Scheme 2).
Conversion to the alcohol facilitates the purification process
as well as rendering a more stable product.
Chiral protected diarylprolinols 7 and 9[15] catalyzed the
transformation with the highest stereoselectivity under our
reaction conditions and mediated the formation of 3a with
high chemoselectivity (Table 1, entries 3 and 5). The highest
enantioselectivity was achieved in toluene. Notably, we
found that the reaction was significantly accelerated by ad-
dition of a base additive, which probably promoted the gen-
eration of the anion of FBSM 2a (Table 1, entries 9–12).
Furthermore, the reaction can be accelerated by heating but
will give a slight decrease in enantioselectivity (Table 1, en-
tries 11 and 12). Based on these results, we decided to inves-
tigate the amine-catalyzed enantioselective FBSM addition
of 2a to enals 1 in toluene with catalyst 7 (Table 2).
Scheme 2. Difficulties encountered when attempting the addition of 1-flu-
oro(phenylsulfonyl)methane to enals.
This report presents highly chemo- and enantioselective
organocatalytic conjugate additions of fluorocarbon nucleo-
philes to a,b-unsaturated aldehydes and the construction of
a quaternary carbon stereocenter bearing a fluorine atom
with high enantioselectivity.
Table 2. Scope of the organocatalytic FBSM additions.[a]
After extensive screening of catalysts and conditions, we
found that chiral amines 5–9 catalyzed the conjugate addi-
tion of FBSM 2a to enal 1a to form the corresponding b-
fluorobisACHTUNGTRENNUNG(sulfonyl)methyl aldehyde 3a, which was reduced
in situ to the alcohol derivative 4a, with enantiomeric excess
(ee) values ranging from nearly racemic to 95%. (Table 1).
R
Prod.
T [8C]
t [h]
Yield [%][b]
ee [%][c]
90[g]
91
89
95
90[g]
1
2
3
4
5
nBu
Me
Et
4a
4b
4c
4d
4e
23
23
23
50
50
20
16
18
2
57[d]
78[e,f]
59
45
65[f]
nPr
16
Table 1. Catalyst screen for the reaction between 1a and 2a.[a]
6
7
8
4 f
4g
4h
50
50
6
16
16
16
84
66
61
87
84
91
[a] Experimental conditions: A mixture of 1 (0.50 mmol) and catalyst 7
(20 mol% relative to 2a) in toluene (0.5 mL) was flushed with argon.
Next, 2a (0.25 mmol) and TEA (10 mol%) were added and the reaction
mixture stirred at the temperature and conditions displayed in the table.
In situ reduction of 3 with NaBH4 gave the corresponding alcohol 4.
[b] Yield of the isolated product 4. [c] Determined by chiral-phase HPLC
analyses of 4. [d] TEA (15 mol%) was added. [e] No TEA was added.
[f] Yield of the isolated aldehyde product 3. [g] The ee value was deter-
mined by chiral-phase HPLC analysis of 3.
Catalyst
Solvent
T [8C]
t [h]
Yield [%][b]
ee [%][c]
1
2
3
4
5
6
7
8
5
6
7
8
9
7
7
7
7
7
7
7
toluene
toluene
toluene
CH3CN
toluene
CH2Cl2
CHCl3
CH3CN
toluene
toluene
toluene
toluene
23
23
23
23
23
23
23
23
23
23
45
60
72
38
24
48
66
48
24
24
<5
64
32
trace
15
41
9
2
95
n.d.
91
84
35
46
88
66
The organocatalytic FBSM reactions were highly chemo-
and enantioselective and the corresponding aldehydes 3
were either isolated or converted to the corresponding alco-
hols 4 by in situ reduction. For example, alcohols 4 were iso-
lated in moderate to high yields with 84–95% ee. The choice
of either reducing or isolating the aldehydes 3 was based on
whether there was any difficulty of separating the aldehydes
from the starting materials. The reduction did not affect the
ee of the product 4 and no 1,2-addition products were ob-
served. The reactions were also highly enantioselective at
508C (Table 2, , entries 4–7). Notably, the reaction is highly
stereoselective for other fluorocarbon nucleophiles, such as
FNSM 2b and 2-fluoro-b-ketoester 2c (Scheme 3). In the
9
20[d]
20[e]
3[e]
1[e,f]
53[d]
57[e]
35[e]
60[e,f]
77[d]
90[e]
91[e]
81[e,f]
10
11
12
[a] Experimental conditions: A mixture of 1a (0.50 mmol) and catalyst
(20 mol% relative to 2a) in solvent (0.5 mL) was flushed with argon.
Next, 2a (0.25 mmol) was added and the reaction mixture stirred at the
temperature and conditions displayed in the table. In situ reduction of 3a
with NaBH4 gave the corresponding alcohol 4a. [b] Yield of the isolated
product 4a after silica-gel column chromatography. [c] Determined by
chiral-phase HPLC analysis of alcohol 4a. [d] Triethylamine (TEA)
(100 mol%) was added. [e] TEA (15 mol%) was added. [f] The reaction
was performed in a sealed tube under microwave irradiation using a mi-
crowave synthesizer from personal systems (Biotage AB).
10014
www.chemeurj.org
ꢁ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2009, 15, 10013 – 10017

Enantioselective Organocatalytic Conjugate Addition
COMMUNICATION
Scheme 5. Conversion of a,b-unsaturated aldehydes to the corresponding
b-FBSM acids. Reaction conditions: i) 7 (20 mol%), toluene, 68C, 16 h;
ii) NaClO2, tBuOH:H2O, RT, 16 h.
Scheme 3. a) Catalytic asymmetric addition of FNSM 2b to 1h. Reaction
conditions: i) 7 (20 mol%), EtOH, 08C, 16 h; ii) NaBH4, MeOH, 08C,
5 min. b) Catalytic asymmetric addition of 2-fluoro-b-ketoester 2c to 1b.
Scheme 6. Desulfonylation of 4h.
case of the conjugate additions with FNSM 2b, the reaction
gave a lower stereoselectivity in toluene as compared with
the addition of FBSM 2a to cinnamic aldehyde (1h). In-
stead, the enantioselectivity was improved, possibly due to
stabilization of the iminium intermediate, by the addition of
an acid additive and performing the transformation in etha-
nol. For example, the reaction between FNSM 2b and cin-
namic aldehyde 1h gave the corresponding alcohol 4i after
in situ reduction in 94% yield with 80:20 dr and 89% ee.
The reaction between commercially available 2c and alde-
hyde 1b afforded aldehyde 3j with a quaternary stereocen-
ter bearing a fluorine atom in 72% yield with 77:23 dr and
88% ee.
Figure 1. ORTEP picture of the crystalline fluorine containing acid 11b.
The enals 1 can also be converted in a one-pot reaction to
monofluorinated cyclohexenone derivatives 10.[13h] This was
exemplified by the asymmetric synthesis of 10b in 65%
yield first by a catalytic asymmetric conjugate addition reac-
tion between 1b and 2c followed by aldol condensation
under acidic conditions (Scheme 4).
Figure 2. Proposed transition state for the enantioselective FBSM reac-
tion with enals.
Scheme 4. One-pot conversion of enals to monofluorinated cyclohex-
ACHTUNGTRENNUNGenone derivatives. Reaction conditions: i) 7 (20 mol%), toluene, RT, 6 h;
ii) p-TSA (20 mol%), 808C, 16 h. p-TSA=toluene sulfonic acid.
count for the stereochemical outcome of the FBSM reac-
tion. Thus, efficient shielding of the Si face of the E-iminium
intermediate I by the bulky group of the chiral amine cata-
lyst 7 allows for enantioselective Re-facial attack by the flu-
orocarbon nucleophiles at the b-carbon to give the corre-
sponding chiral enamine intermediate. Subsequent hydroly-
sis of iminium intermediate II gives the corresponding alde-
hyde products 3 (Scheme 7).
In summary, we report the highly chemo- and enantiose-
lective organocatalytic addition of fluorocarbon nucleophiles
such as FBSM to a,b-unsaturated aldehydes. The reaction is
catalyzed by simple chiral pyrrolidine derivatives and gives
the corresponding monofluoro derivatives in moderate to
high yields with up to 95% ee. The methodology can also be
Moreover, the a,b-unsaturated aldehydes 1 can be con-
verted in one pot or two steps to the corresponding b-FBSM
acids 11 (Scheme 5). For example, carboxylic acid 11b was
prepared in 65% yield with 91% ee. Furthermore, alcohols
4 can be desulfonylated to the corresponding fluoromethy-
lated alcohols 12 (Scheme 6). This was demonstrated by
converting alcohol 4h with Mg in methanol to the alcohol
derivative 12h.[8a]
Based on the X-ray analysis of a single crystal of acid
(2R)-11b[16] (Figure 1) and transition-state theory of catalyst
7,[15] we propose the transition state shown in Figure 2 to ac-
Chem. Eur. J. 2009, 15, 10013 – 10017
ꢁ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
10015

A. Cꢀrdova et al.
Kollonitsch, A. A. Patchett, S. Marburg, A. L. Maycock, L. M. Per-
kins, G. A. Doldouras, D. E. Duggan, S. D. Aster, Nature 1978, 274,
906; c) R. B. Silverman, S. M. Nanavati, J. Med. Chem. 1990, 33, 931.
[4] a) L. Hintermann, A. Togni, Angew. Chem. 2000, 112, 4530; Angew.
Chem. Int. Ed. 2000, 39, 4359.
[5] a) H. Ibrahim, A. Togni, Chem. Commun. 2004, 1147; b) J. A. Ma,
D. Cahard, Chem. Soc. Rev. 2004, 33, 6119; c) C. Bobbio, V. Gouver-
neur, Org. Biomol. Chem. 2006, 4, 2065; d) M. Oestreich, Angew.
Chem. 2005, 117, 2376; Angew. Chem. Int. Ed. 2005, 44, 2324;
e) P. M. Pihko, Angew. Chem. 2006, 118, 558; Angew. Chem. Int. Ed.
2006, 45, 544.
[6] For selected examples of the use of NFSI, see: a) Y. Hamashima, K.
Yagi, H. Takano, L. Tamꢃs, M. Sodeoka, J. Am. Chem. Soc. 2002,
124, 14530; b) D. Y. Kim, E. J. Park, Org. Lett. 2002, 4, 545; c) P. Y.
Toullec, C. Bonacorsi, A. Mezzeti, A. Togni, Proc. Natl. Acad. Sci.
USA 2004, 101, 5810; d) T. Suzuki, Y. Hamashima, M. Sodeoka,
Angew. Chem. 2007, 119, 5531; Angew. Chem. Int. Ed. 2007, 46,
5435; e) D. S. Reddy, N. Shibata, J. Nagai, S. Nakamura, T. Toru, S.
Kanemasa, Angew. Chem. 2008, 120, 170; Angew. Chem. Int. Ed.
2008, 47, 164.
[7] For selected organocatalytic examples, see: a) N. Shibata, E. Suzuki,
Y. Takeuchi, J. Am. Chem. Soc. 2000, 122, 10728; b) B. Greedy, J. M.
Paris, T. Vidal, V. Gouverneur, Angew. Chem. 2003, 115, 3413;
Angew. Chem. Int. Ed. 2003, 42, 3291; c) D. Enders, M. R. M. Hꢂttl,
Synlett 2005, 0991; d) M. Marigo, D. Fielenbach, A. Braunton, A.
Kjoersgaard, K. A. Jørgensen, Angew. Chem. 2005, 117, 3769;
Angew. Chem. Int. Ed. 2005, 44, 3703; e) D. D. Steiner, N. Mase,
C. F. Barbas III, Angew. Chem. 2005, 117, 3772; Angew. Chem. Int.
Ed. 2005, 44, 3706; f) T. D. Beeson, D. W. C MacMillan, J. Am.
Chem. Soc. 2005, 127, 8826; g) S. Brandes, B. Niess, M. Bella, A.
Prieto, J. Overgaard, K. A. Jørgensen, Chem. Eur. J. 2006, 12, 6039;
h) T. Ishimaru, N. Shibata, T. Horikawa, N. Yasuda, S. Nakamura, T.
Toru, M. Shiro, Angew. Chem. 2008, 120, 4225; Angew. Chem. Int.
Ed. 2008, 47, 4157.
[8] a) T. Furukawa, N. Shibata, S. Mizuta, S. Nakamura, T. Toru, M.
Shiro, Angew. Chem. 2008, 120, 8171; Angew. Chem. Int. Ed. 2008,
47, 8051; b) G. K. S. Prakash, F. Wang, T. Stewart, T. Mathew, G. A.
Olah, Proc. Natl. Acad. Sci. USA 2009, 106, 4090; during the prepa-
ration of this manuscript two elegant papers appeared describing
the addition of 2-fluoro-b-ketoesters to electrophiles employing bi-
cyclic guanidines and cinchona alkaloid catalysts, respectively: c) Z.
Jiang, Y. Pan, Y. Zhao, T. Ma, R. Lee, Y. Yang, K.-W. Huang, M. W.
Wong, C.-H. Tan, Angew. Chem. 2009, 121, 3681; Angew. Chem. Int.
Ed. 2009, 48, 3627; d) H. Li, S. Zhang, C. Yu, X. Song, W. Wang,
Chem. Commun. 2009, 2136.
Scheme 7. Proposed mechanism for the chiral amine-catalyzed enantiose-
lective additions of fluorocarbon nucleophiles to enals.
applied to the addition of other fluorocarbon nucleophiles
and to the generation of a chiral quaternary carbon center
bearing a fluorine atom with high enantioselectivity. Mecha-
nistic studies and synthetic applications of this transforma-
tion, as well as the development of other enantioselective
nucleophilic fluorinations based on this concept are ongoing
in our laboratory.[17]
Experimental Section
Details of the experiments carried out can be found in the Supporting In-
formation.
[9] a) T. Fukuzumi, N. Shibata, M. Sugiura, H. Yasui, S. Nakamura, T.
Toru, Angew. Chem. 2006, 118, 5095; Angew. Chem. Int. Ed. 2006,
45, 4973; b) S. Mizuta, N. Shibata, Y. Goto, T. Furukawa, S. Naka-
mura, T. Toru, J. Am. Chem. Soc. 2007, 129, 6394.
[10] a) G. K. S. Prakash, S. Chako, S. Alconcel, T. Stewart, T. Mathew,
G. A. Olah, Angew. Chem. 2007, 119, 5021; Angew. Chem. Int. Ed.
2007, 46, 4933; b) G. K. S. Prakash, X. Zhao, S. Chacko, F. Wang, H.
Vaghoo, G. A. Olah, Beilstein J. Org. Chem. 2008, 4: 1.
Acknowledgements
We gratefully acknowledge the Swedish National Research Council,
Magn Bergvall Foundation, and Carl Trygger Foundation for financial
support.
[11] a) C. Ni, Y. Li, J. Hu, J. Org. Chem. 2006, 71, 6289; b) C. Ni, L.
Zhang, J. Hu, J. Org. Chem. 2008, 73, 5699.
Keywords: aldehydes
chemoselectivity · fluorine · organocatalysis
·
asymmetric
catalysis
·
[12] For selected reviews, see: a) A. Berkessel, H. Grçger, Asymmetric
Organocatalysis, Wiley-VCH, Weinheim, 2004; b) S. Mukherjee,
J. W. Yang, S. Hoffmann, B. List, Chem. Rev. 2007, 107, 5471; c) A.
Erkkilꢄ, I. Majander, P. M. Pihko, Chem. Rev. 2007, 107, 5416; d) M.
Marigo, K. A. Jørgensen, Chem. Commun. 2006, 2001.
[13] For selected examples, see: a) K. A. Ahrendt, C. J. Borths, D. W. C.
MacMillan, J. Am. Chem. Soc. 2000, 122, 4243; b) A. B. Northrup,
D. W. C. MacMillan, J. Am. Chem. Soc. 2002, 124, 2458; c) R. K.
Kunz, D. W. C. MacMillan, J. Am. Chem. Soc. 2005, 127, 3240;
d) W. S. Jen, J. J. M. Wiener, D. W. C. MacMillan, J. Am. Chem. Soc.
2000, 122, 9874; e) N. Halland, P. S. Aburell, K. A. Jørgensen,
Angew. Chem. 2004, 116, 1292; Angew. Chem. Int. Ed. 2004, 43,
1272; f) S. Brandau, A. Landa, J. Franzen, M. Marigo, K. A. Jørgen-
sen, Angew. Chem. 2006, 118, 4411; Angew. Chem. Int. Ed. 2006, 45,
[1] a) Organofluorine Compounds in Medicinal Chemistry and Biomedi-
cal Applications (Eds.: R. Filler, Y. Kobayashim, L. M. Yagupolskii),
Elsevier, Amsterdam, 1993; b) P. Kirsch, Modern Fluoroorganic
Chemistry, Wiley-VCH, Weinheim, 2004; c) T. Hiyama in Organo-
fluorine Compounds: Chemistry and Applications, Springer, Berlin,
2000.
[2] a) K. Mꢂller, C. Faeh, D. Diederich, Science 2007, 317, 1881; b) S.
Purser, P. R. Moore, S. Swallow, V. Gouverneur, Chem. Soc. Rev.
2008, 37, 320.
[3] a) G. L. Grunewald, T. M. Caldwell, Q. Li, M. Slavica, K. R. Cris-
cione, R. T. Borchardt, W. Wang, J. Med. Chem. 1999, 42, 3588; b) J.
10016
www.chemeurj.org
ꢁ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2009, 15, 10013 – 10017

Enantioselective Organocatalytic Conjugate Addition
COMMUNICATION
4305; g) A. Carlone, S. Cabrera, M. Marigo, K. A. Jørgensen,
Angew. Chem. 2007, 119, 1119; Angew. Chem. Int. Ed. 2007, 46,
1101, and references therein; h) A. Carlone, M. Marigo, C. North,
A. Landa, K. A. Jørgensen, Chem. Commun. 2006, 4928; i) H.
Gotoh, R. Masui, H. Ogino, M . Shoji, Y. Hayashi, Angew. Chem.
2006, 118, 7007; Angew. Chem. Int. Ed. 2006, 45, 6853; j) S. Hanessi-
an, V. Pham, Org. Lett. 2000, 2, 2975.
128, 10354; o) R. Rios, H. Sunden, I. Ibrahem, G. L. Zhao, L. Eriks-
son, A. Cꢀrdova, Tetrahedron Lett. 2006, 47, 8547; p) S. Brandau, E.
Maerten, K. A. Jørgensen, J. Am. Chem. Soc. 2006, 128, 14986. For
selected examples of oxygen nucleophiles, see: q) S. Bertelsen, P.
Dinꢅr, R. L. Johansen, K. A. Jørgensen, J. Am. Chem. Soc. 2007,
129, 1536; r) T. Govender, L. Hojabri, F. M. Moghaddam, P. I. Ar-
vidsson, Tetrahedron: Asymmetry 2006, 17, 1763; s) H. Sundꢅn, I.
Ibrahem, G. L. Zhao, L. Eriksson, A. Cꢀrdova, Chem. Eur. J. 2007,
13, 574; t) A. Pohjakallio, P. M. Pihko, Chem. Eur. J. 2009, 15, 3960;
for selected examples of phosphorus nucleophiles, see: u) I. Ibra-
hem, R. Rios, J. Vesely, P. Hammar, L. Eriksson, F. Himo, A. Cꢀrdo-
va, Angew. Chem. 2007, 119, 4591; Angew. Chem. Int. Ed. 2007, 46,
4507; v) A. Carlone, G. Bartoli, M. Bosco, L. Sambri, P. Melchiorre,
Angew. Chem. 2007, 119, 4588; Angew. Chem. Int. Ed. 2007, 46,
4504.
[14] For selected examples of hydrido nucleophiles, see: a) J. W. Yang,
M. T. Hechevarria Fonseca, N. Vignola, B. List, Angew. Chem. 2005,
117, 110; Angew. Chem. Int. Ed. 2005, 44, 108; b) S. G. Guellet, J. B.
Tuttle, D. W. C. MacMillan, J. Am. Chem. Soc. 2005, 127, 32; c) S.
Mayer, B. List, Angew. Chem. 2006, 118, 4299; Angew. Chem. Int.
Ed. 2006, 45, 4193; d) R. M. Wilson, W. S. Jen, D. W. C. MacMillan,
J. Am. Chem. Soc. 2005, 127, 11616; e) G. L. Zhao, A. Cꢀrdova, Tet-
rahedron Lett. 2006, 47, 7417; for selected examples of nitrogen nu-
cleophiles, see: f) Y. K. Chen, M. Yoshida, D. W. C. MacMillan, J.
Am. Chem. Soc. 2006, 128, 9328; g) I. Ibrahem, R. Rios, J. Vesely,
G.-L. Zhao, A. Cꢀrdova, Chem. Commun. 2006, 849; h) H. Sundꢅn,
R. Rios, I. Ibrahem, G.-L. Zhao, L. Eriksson, A. Cꢀrdova, Adv.
Synth. Catal. 2007, 349, 827; i) J. Vesely, I. Ibrahem, R. Rios, G. L.
Zhao, Y. Xu, A. Cꢀrdova, Tetrahedron Lett. 2007, 48, 2193; j) P.
Dinꢅr, M. Nielsen, M. Marigo, K. A. Jørgensen, Angew. Chem. 2007,
119, 1983; k) J. Vesely, I. Ibrahem, G.-L. Zhao, R. Rios, A. Cꢀrdova,
Angew. Chem. 2007, 119, 792; Angew. Chem. Int. Ed. 2007, 46, 778;
l) G. L. Zhao, R. Rios, J. Vesely, L. Eriksson, A. Cꢀrdova, Angew.
Chem. 2008, 120, 8596; Angew. Chem. Int. Ed. 2008, 47, 8468; for se-
lected examples of sulfur nucleophiles see: m) M. Marigo, T.
Schulte, J. Franzen, K. A. Jørgensen, J. Am. Chem. Soc. 2005, 127,
15710; n) W. Wang, H. Li, J. Wang, L. Zu, J. Am. Chem. Soc. 2006,
[15] See reference [7d] and a) Y. Hayashi, H. Gotoh, T. Hayashi, M.
Shoji, Angew. Chem. 2005, 117, 4284; Angew. Chem. Int. Ed. 2005,
44, 4212; b) for a review, see: A. Mielgo, C. Palomo, Chem. Asian J.
2008, 3, 922.
[16] CCDC 730063 contains 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.
[17] After the submission of our manuscript a similar paper describing
the FBSM reaction appeared, see: A.-M. Alba, X. Companyo, A.
Moyano, R. Rios, Chem. Eur. J. 2009, 15, 7035.
Received: May 12, 2009
Published online: August 31, 2009
Chem. Eur. J. 2009, 15, 10013 – 10017
ꢁ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
10017