Enantioselective synthesis of α-alkylidene-γ-butyrolactones: Intramolecular rauhut-currier reaction promoted by acid/base organocatalysts

Article abstract of DOI:10.1002/anie.201201542

Teaming up: The title reaction has been developed to deliver the product α-alkylidene-γ-butyrolactones as single diastereomers with up to 98 %ee (see scheme; Ts=4-toluenesulfonyl). The enantioselective process is catalyzed by 1, which contains both Lewis

Full text of DOI:10.1002/anie.201201542

Angewandte
Chemie
DOI: 10.1002/anie.201201542
Asymmetric Catalysis
Enantioselective Synthesis of a-Alkylidene-g-Butyrolactones:
Intramolecular Rauhut–Currier Reaction Promoted by Acid/Base
Organocatalysts**
Shinobu Takizawa, Tue Minh-Nhat Nguyen, Andrꢀ Grossmann, Dieter Enders, and
Hiroaki Sasai*
In a little over a decade, enantioselective organocatalysis has
been developed as a complementary methodology to metal-
and biocatalysis in synthetic organic chemistry.[1] Among the
achievements, carbon–carbon bond-forming reactions using
chiral organocatalysts play an outstanding role in enabling the
highly selective creation of useful skeletons for natural
product synthesis.[2] The Rauhut–Currier (RC) reaction is
known to provide ready access to a-substituted enones
through the coupling of two different a,b-unsaturated car-
bonyl compounds, one of which serves as a latent enolate.[3,4]
To date, attractive systems based on achiral catalysis have
been developed for the RC process,[5] although few examples
of synthetically useful enantioselective RC transformations
have been reported. The first breakthrough in the enantio-
selective RC reaction was reported by Aroyan and Miller[6a] in
2007 with further contributions by the groups of Gladysz,[6b]
Christmann,[6c] and Wu.[6d] These groups succeeded in the
development of the enantioselective cycloisomerization of
bis(enones) or enal-enones.[6] Meanwhile, Gu, Xiao, and co-
workers extended this reaction to nitroolefins.[7] Scheidt and
co-workers[8a] and Shi and co-workers[8b] presented the
intermolecular RC reaction of silyloxyallenes and allenoates
catalyzed by Sc(OTf)3/(R,R)-Ph-Pybox or b-ICD. Highly
selective construction of complex frameworks through the
enantioselective RC reaction has been a challenge in asym-
metric synthetic chemistry.
We envisioned that the desymmetrization of the prochiral
dienones 2, which are easily accessible from readily available
materials, by the RC reaction as a straightforward and atom-
economical way to prepare a-alkylidene-g-butyrolactones
1 (Figure 1).[9] The a-alkylidene-g-butyrolactone skeleton is
Figure 1. Retrosynthetic analysis of compound 1 and examples of
a-alkylidene-g-butyrolactones isolated from natural sources.
[*] Dr. S. Takizawa, T. M.-N. Nguyen, Prof. Dr. H. Sasai
The Institute of Scientific and Industrial Research (ISIR), Osaka
University, Mihogaoka, Ibaraki-shi
Osaka 567-0047 (Japan)
E-mail: sasai@sanken.osaka-u.ac.jp
Homepage: http://www.sanken.osaka-u.ac.jp/labs/soc/soc-
main.html
common to a vast number of natural products, such as
paeonilactone B (5), calealactone C (6), and the tricyclic
compounds 7 and 8, which exhibit various biological activities
(e.g. anticancer, antimalarial, antiviral, antibacterial, antifun-
gal, anti-inflammatory, etc.; Figure 1).[10]
As the first step in the development of the designated RC
reaction, achiral Lewis base (LB) catalysts were evaluated
using 2a as a prototypical substrate (Table 1). The Morita–
Baylis–Hillman (MBH) reaction is known to be accelerated in
the presence of a Brønsted acid.[11] Given the similarity of the
MBH and RC reactions, phenol (50 mol%) was added to the
reaction of 2a to increase the reaction rate.[12] To our delight,
PPh3 was found to efficiently promote the reaction and the
desired product 1a was obtained in 81% yield (Table 1,
entry 1). In contrast, PPh3 without phenol (entry 2) or an
A. Grossmann, Prof. Dr. D. Enders
Institute of Organic Chemistry, RWTH Aachen University
Landoltweg 1, 52074 Aachen (Germany)
[**] This work was supported by the CREST project of the Japan Science
and Technology Corporation (JST) and a Grant-in-Aid for Scientific
Research from the Ministry of Education, Culture, Sports, Science,
and Technology (Japan). We thank the Deutsche Forschungsge-
meinschaft (scholarship for A.G., International Research Training
Group “Selectivity in Chemo- and Biocatalysis”—SeleCa (Ger-
many)). We acknowledge the technical staff of the Comprehensive
Analysis Center of ISIR, Osaka University (Japan).
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201201542.
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Table 1: Achiral LB catalyzed RC reaction.
Table 2: Enantioselective RC reaction using organocatalysts.
Entry
Chiral
t [h]
Yield [%][a]
ee [%][b]
organocatalyst
Entry
Achiral
LB catalyst
Solvent
Additive
Yield
[%][a]
1
2
3
4
5
6
7
8
b-ICD or 9–15
(S)-binap
(S)-mop
(Rc,Sp)-ppfa
(Sc,Rp)-bppfa
(Sc,Rp)-bppfoh
(R)-16a
(R)-16b
(S)-16c
(S)-16c
(S)-16c
48
18
22
18
19
19
18
20
19
48
24
24
no reaction
6
–
20
0
20
9
9
60
–
80
93
93
98
1
2
3
PPh3
PPh3
CH2Cl2
CH2Cl2
CH2Cl2
phenol
none
phenol
81
16
<10
16
72
13
3
52
trace
77
80
87
99
DMAP, DBU
or DABCO
[b]
4
5
6
7
8
9
PPh3
CH2Cl2
CH3Cl
toluene
MeCN
THF or MeOH
CH2Cl2
phenol
phenol
phenol
phenol
phenol
(S)-binol
63
53
72
65
PPh3
PPh3
PPh3
PPh3
PPh3
9
10[c]
11[c,d]
12[c,d,e]
trace
37[c]
(S)-16c
[a] Determined by 1H NMR spectroscopy. [b] 20 mol%. [c] rac-1a was
obtained. Binol=1,1’-bi-2-naphthol, DABCO=diazabicyclo-
[2.2.2]octane, DBU=1,8-diazabicyclo[5.4.0]undec-7-ene, DMAP=
4-(dimethylamino)pyridine.
[a] Determined by 1H NMR spectroscopy. [b] Determined by HPLC
(Daicel Chiralpak IC). [c] At 08C. [d] Without phenol. [e] In CHCl3.
Ts =4-toluenesulfonyl.
amine catalyst such as DMAP, DBU, or DABCO (entry 3)
barely catalyzed the cycloisomerization reaction, thus afford-
ing a low yield of 1a.[5a,b] Reduction of the catalyst loading to
20 mol% still maintained a moderate yield (entry 4). Among
the solvents tested, halogenated solvents (entries 1 and 5),
toluene (entry 6), and MeCN (entry 7) provided 1a in
moderate to good yields. When (S)-binol was used as
a chiral Brønsted acid, no asymmetric induction onto 1a
was observed (entry 9).
Next, various chiral catalysts were tested as shown in
Table 2. b-ICD and catalysts 9–15, some of which are known
to mediate the enantioselective MBH-type processes,[11,13]
showed no activity (Table 2, entry 1). (S)-binap and (S)-mop
gave the product but in low yields with low or no selectivity
(entries 2 and 3). The ferrocenyl phosphine (Rc,Sp)-ppfa
promoted the reaction in 72% yield and 20% ee (entry 4),
whereas (Sc,Rp)-bppfa and (Sc,Rp)-bppfoh exhibited low
catalytic activities (entries 5 and 6). During this screening
process, the chiral organocatalysts 16, possessing a highly
nucleophilic phosphine as a result of its connection at the
phosphorus atom to a primary carbon atom, caught our
attention.[11h] As expected, (R)-16a was able to promote the
RC reaction to afford 1a in 52% yield and 60% ee (entry 7).
In contrast, no catalytic activity was observed using the
phosphinothiourea catalyst 16b[6d,14] (entry 8). Finally the
acid/base organocatalyst (S)-16c[15] was found to yield an
acceptable outcome with over 80% ee (entries 9–12). A lower
reaction temperature also led to a drastic improvement in the
enantioselectivity (entry 10). In the absence of phenol,
a higher reaction rate was observed and the high enantiose-
lectivity was maintained (entry 11). The best result (99%
yield, 98% ee) was obtained when the reaction was performed
in CHCl3 at 08C in the absence of phenol (entry 12).
determined to be cis configured by using NOESY experi-
ments conducted on 1a. In all cases, a single diastereomer was
obtained.[16] The aliphatic substrates 2b–e were cyclized with
high enantioselectivity (95–98% ee), although a higher cata-
lyst loading and longer reaction times were needed
(30 mol%, 72 h). Interestingly, aromatic-substituted sub-
strates were more reactive than aliphatic substrates.[17] The
reaction of the aromatic-substituted substrates 2 f–j afforded
the corresponding products 1 f–j in good yields (82–97%)
with high enantioselectivities (90–98% ee).
The construction of a structural motif bearing two
contiguous, quaternary, stereogenic centers is considered
challenging in organic synthesis.[18] When substrate 2k was
subjected to this enantioselective reaction, the corresponding
lactone 1k was obtained in 56% yield and 70% ee. To
improve the yield and enantioselectivity, phenol (50 mol%)
With the optimized reaction conditions in hand, attention
was given to the substrate scope (Scheme 1). Aliphatic- and
aromatic-substituted starting materials (2) were successfully
cyclized to give the a-alkylidene-g-butyrolactones 1 in good
yields and high enantioselectivities. The lactones were
2
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Scheme 2. Proposed mechanism of the RC reaction.
proton transfer from the a position of a carbonyl group of the
lactone to the enolate anion in B through the BA moiety
results in the formation of the chiral a-alkylidene-g-butyro-
lactone 1, along with regeneration of the organocatalyst
through a retro-Michael reaction. Since the BA moiety plays
an important role in smoothly promoting the reaction,[20] we
agree with the report, presented by Miller and co-workers on
the bis(enone) cyclization, which states that the proton-
transfer step is rate determining.[6a,e]
In conclusion, we have developed a highly atom-econom-
ical, chemo-, diastereo-, and enantioselective approach to the
medicinally important a-alkylidene-g-butyrolactone core
using an organocatalytic Rauhut–Currier reaction. Further
investigation of the reaction mechanism and the application
of this method to natural product synthesis are underway and
will be reported in due course.
Experimental Section
General procedure: A screw-cap tube was charged with the catalyst
(S)-16c (0.05--0.08 mmol, 20--30 mol%) and a solution of dienone 2
(0.25 mmol) in chloroform (0.5 mL) at 08C. The reaction mixture was
stirred until the reaction reached completion as determined by TLC
analysis. After purification by column chromatography on silica gel
(hexanes/ethylacetate 1:1) the desired product 1 was obtained as
a colorless oil or a white solid.
Scheme 1. Scope of the enantioselective RC reaction. Yields of isolated
1. The ee values of 1 were determined by HPLC (Daicel Chiralpak IA,
IB, IC, AD or AD3). [b] Reaction conditions: (S)-16c (30 mol%),
CHCl3, 08C, 72 h. [c] Phenol (50 mol%) was used with the optimized
reaction conditions.
was added as an extraneous proton shuttle. An increase in the
ee value to 96% was established, albeit along with significant
reduction in the chemical yield.
Received: February 25, 2012
Published online: && &&, &&&&
Keywords: asymmetric catalysis · lactones · Michael addition ·
The proposed mechanism of the RC reaction using the
chiral catalyst 16c bearing both Brønsted acid (BA; -NHTs)
and Lewis base (-PPh2) moieties is shown in Scheme 2. First
the Michael addition of the LB moiety to the acrylate unit of 2
generates the phosphonium enolate A,[19] which is stabilized
by the BA. Second, the enolate A reacts with one of the
olefins on the dienone. This second Michael addition results
in the formation of the intermediate B. To avoid steric
interactions between the iPr substituent of the chiral catalyst
16c and the R substituent in the substrate, the reaction using
(S)-16c favors the (S,S)-configured intermediate B. Finally,
.
organocatalysis · synthetic methods
[1] For selected reviews on organocatalysis, see: a) A. Berkessel, H.
Grçger, Asymmetric Organocatalysis, Wiley-VCH, Weinheim,
2005; b) P. I. Dalko, Enantioselective Organocatalysis: Reactions
and Experimental Procedures, Wiley-VCH, Weinheim, 2007;
c) H. Pellissier, Tetrahedron 2007, 63, 9267; d) Special issue on
organocatalysis (Ed.: B. List): Chem. Rev. 2007, 107, 5413; e) R.
Marcia De Figueiredo, M. Christmann, Eur. J. Org. Chem. 2007,
2575; f) A. Dondoni, A. Massi, Angew. Chem. 2008, 120, 4716;
Angew. Chem. Int. Ed. 2012, 51, 1 – 5
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
3
These are not the final page numbers!

.
Angewandte
Communications
Angew. Chem. Int. Ed. 2008, 47, 4638; g) D. W. C. MacMillan,
Nature 2008, 455, 304; h) S. Bertelsen, K. A. Jørgensen, Chem.
Soc. Rev. 2009, 38, 2178; i) M. Nielsen, D. Worgull, T. Zweifel, B.
Gschwend, S. Bertelsen, K. A. Jørgensen, Chem. Commun. 2011,
47, 632.
Acc. Chem. Res. 2010, 43, 1005; h) S.-X. Wang, X. Han, F. Zhong,
Y. Wang, Y. Lu, Synlett 2011, 2766.
[12] S. Ikegami, Y. M. A. Yamada, Tetrahedron Lett. 2000, 41, 2165.
[13] a) Y. Iwabuchi, M. Nakatani, N. Yokoyama, S. Hatakeyama, J.
Am. Chem. Soc. 1999, 121, 10219; b) M. Shi, Y.-M. Xu, Angew.
Chem. 2002, 114, 4689; Angew. Chem. Int. Ed. 2002, 41, 4507;
c) S. Kawahara, A. Nakano, T. Esumi, Y. Iwabuchi, S. Hatake-
tyama, Org. Lett. 2003, 5, 3103; d) M. Shi, L. H. Chen, Chem.
Commun. 2003, 1310; e) K. Matsui, S. Takizawa, H. Sasai, J. Am.
Chem. Soc. 2005, 127, 3680; f) M. Shi, L.-H. Chen, C.-Q. Li, J.
Am. Chem. Soc. 2005, 127, 3790; g) K. Matsui, S. Takizawa, H.
Sasai, Synlett 2006, 761; h) K. Matsui, K. Tanaka, A. Horii, S.
Takizawa, H. Sasai, Tetrahedron: Asymmetry 2006, 17, 578; i) S.
Takizawa, N. Inoue, S. Hirata, H. Sasai, Angew. Chem. 2010, 122,
9919; Angew. Chem. Int. Ed. 2010, 49, 9725; j) S. Takizawa, N.
Inoue, H. Sasai, Tetrahedron Lett. 2011, 52, 377; k) S. Takizawa,
K. Kiriyama, K. Ieki, H. Sasai, Chem. Commun. 2011, 47, 9227;
l) H.-P. Deng, M. Shi, Eur. J. Org. Chem. 2012, 183.
[2] a) M. J. Gaunt, C. C. C. Johansson, A. McNally, N. T. Vo, Drug
Discovery Today 2007, 12, 8; b) D. Enders, C. Grondal, M. R. M.
Huttl, Angew. Chem. 2007, 119, 1590; Angew. Chem. Int. Ed.
2007, 46, 1570; c) A. M. Walji, D. W. C. MacMillan, Synlett 2007,
1477; d) L.-W. Xu, J. Luo, Y. Lu, Chem. Commun. 2009, 1807;
e) M. G. NfflÇez, P. García, R. F. Moro, D. Díez, Tetrahedron
2010, 66, 2089; f) C. Grondal, M. Jeanty, D. Enders, Nat. Chem.
2010, 2, 167; g) H. Ishikawa, M. Honma, Y. Hayashi, Angew.
Chem. 2011, 123, 2876; Angew. Chem. Int. Ed. 2011, 50, 2824.
[3] M. M. Rauhut, H. Currier (American Cyanamid Co.), U.S.
Patent 3074999, 1963.
[4] For a short review on the RC reaction, see: C. E. Aroyan, A.
Dermenci, S. J. Miller, Tetrahedron 2009, 65, 4069.
[5] a) L.-C. Wang, A. L. Luis, K. Agapiou, H.-Y. Jang, M. J. Krische,
J. Am. Chem. Soc. 2002, 124, 2402; b) S. A. Frank, D. J. Mergott,
W. R. Roush, J. Am. Chem. Soc. 2002, 124, 2404; c) D. J.
Mergott, S. A. Frank, W. R. Roush, Org. Lett. 2002, 4, 3157;
d) J. L. Methot, W. R. Roush, Org. Lett. 2003, 5, 4223; e) S. M.
Winbush, D. J. Mergott, W. R. Roush, J. Org. Chem. 2008, 73,
1818; f) F. O. Seidel, J. A. Gladysz, Adv. Synth. Catal. 2008, 350,
2443; g) W. Yao, Y. Wu, G. Wang, Y. Zhang, C. Ma, Angew.
Chem. 2009, 121, 9893; Angew. Chem. Int. Ed. 2009, 48, 9713;
h) Y. Qiao, S. Kumar, W. P. Malachowski, Tetrahedron Lett. 2010,
51, 2636; i) W. Liu, J. Zhou, C. Zheng, X. Chen, H. Xiao, Y. Yang,
Y. Guo, G. Zhao, Tetrahedron 2011, 67, 1768; j) J. Ma, P. Xie, C.
Hu, Y. Huang, R. Chen, Chem. Eur. J. 2011, 17, 7418.
[6] Enantioselective RC reaction utilizing cysteine-derived thio-
lates; also see Refs. [6e-g]: a) C. E. Aroyan, S. J. Miller, J. Am.
Chem. Soc. 2007, 129, 256; rhenium phosphine complexes, b) F.
Seidel, J. A. Gladysz, Synlett 2007, 986; prolinol derivatives with
AcOH, c) E. MarquØs-López, R. P. Herrera, T. Marks, W. C.
Jacobs, D. Kçnning, R. M. de Figueiredo, M. Christmann, Org.
Lett. 2009, 11, 4116; valine-derived phosphinothioureas, d) J.-J.
Gong, T.-Z. Li, K. Pan, X.-Y. Wu, Chem. Commun. 2011, 47,
1491; e) C. E. Aroyan, A. Dermenci, S. J. Miller, J. Org. Chem.
2010, 75, 5784; f) P. S. Selig, S. J. Miller, Tetrahedron Lett. 2011,
52, 2148; g) A. Dermenci, P. S. Selig, R. A. Domaoal, K. A.
Spasov, K. S. Anderson, S. J. Miller, Chem. Sci. 2011, 2, 1568;
h) B. J. Cowen, S. J. Miller, J. Am. Chem. Soc. 2007, 129, 10988.
[7] X.-F. Wang, L. Peng, J. An, C. Li, Q.-Q. Yang, L.-Q. Lu, F.-L. Gu,
W.-J. Xiao, Chem. Eur. J. 2011, 17, 6484.
[14] In the absence of phenol, the reaction of 2a using catalyst 16b
(20 mol%) gave the product 1a in 12% yield with 60% ee after
24 h.
[15] I. J. Krauss, J. L. Leighton, Org. Lett. 2003, 5, 3201.
[16] The absolute configuration of 1 was assigned by comparison with
an optical rotation of the synthetic analogue reported in the
literature. R. Sunasee, D. L. J. Clive, Chem. Commun. 2010, 46,
701.
[17] This discrepancy in reactivity would be attributable to the
Thorpe – Ingold effect. R. M. Beesley, C. K. Ingold, J. F. Thorpe,
J. Chem. Soc. Trans. 1915, 107, 1080.
[18] For a discussion on synthesis of natural products bearing
contiguous, quaternary, stereogenic centers, see: E. A. Peterson,
L. E. Overman, Proc. Natl. Acad. Sci. USA 2004, 101, 11943.
[19] The 31P NMR spectroscopic data of 2a with 16c (1 equiv) and
phenol (10 equiv) indicate
a signal corresponding to the
phosphonium enone C (d = 28.9 ppm) via the intermediate A.
The structure of C was supported by the 1H and 13C NMR
spectroscopic data and HRMS (ESI).
A few hours later
compound 17 was obtained as a decomposition product from C.
[8] a) T. E. Reynolds, M. S. Binkley, K. A. Scheidt, Org. Lett. 2008,
10, 2449; b) Q.-Y. Zhao, C.-K. Pei, X.-Y. Guan, M. Shi, Adv.
Synth. Catal. 2011, 353, 1973.
[9] For recent reviews on the synthesis of a-alkylidene-g-butyrolac-
tones, see: a) R. R. A. Kitson, A. Millemaggi, R. J. K. Taylor,
Angew. Chem. 2009, 121, 9590; Angew. Chem. Int. Ed. 2009, 48,
9426; b) P. V. Ramachandran, M. Yip-Schneider, C. M. Schmidt,
Future Med. Chem. 2009, 1, 179.
[10] a) E. Rodriguez, G. H. N. Towers, J. C Mitchell, Phytochemistry
1976, 15, 1573; b) K. Picman, Biochem. Syst. Ecol. 1986, 14, 255;
c) A. Ghantous, H. Gali-Muhtasib, H. Vuorela, N. A. Saliba, N.
Darwiche, Drug Discovery Today 2010, 15, 668.
[11] For recent reviews on the MBH reaction, see: a) G. Masson, C.
Housseman, J. Zhu, Angew. Chem. 2007, 119, 4698; Angew.
Chem. Int. Ed. 2007, 46, 4614; b) G.-N. Ma, J.-J. Jiang, M. Shi, Y.
Wie, Chem. Commun. 2009, 5496; c) V. Declerck, J. Martinez, F.
Lamaty, Chem. Rev. 2009, 109, 1; d) V. Carrasco-Sanchez, M. J.
Simirgiotis, L. S. Santos, Molecules 2009, 14, 3989; e) D. Basa-
vaiah, B. S. Reddy, S. S. Badsara, Chem. Rev. 2010, 110, 5447; f) J.
Mansilla, J. M. Saµ, Molecules 2010, 15, 709; g) Y. Wei, M. Shi,
[20] a) L. S. Santos, C. H. Pavam, W. P. Almeida, F. Coelho, M. N.
Eberlin, Angew. Chem. 2004, 116, 4430; Angew. Chem. Int. Ed.
2004, 43, 4330; b) V. K. Aggarwal, S. Y. Fulford, G. C. Lloyd-
Jones, Angew. Chem. 2005, 117, 1734; Angew. Chem. Int. Ed.
2005, 44, 1706; c) K. E. Price, S. J. Broadwater, H. M. Jung, D. T.
McQuade, Org. Lett. 2005, 7, 147; d) I. T. Raheem, E. N.
Jacobsen, Adv. Synth. Catal. 2005, 347, 1701; e) K. E. Price,
S. J. Broadwater, B. J. Walker, D. T. McQuade, J. Org. Chem.
2005, 70, 3980; f) P. Buskens, J. Klankermayer, W. Leitner, J. Am.
Chem. Soc. 2005, 127, 16762; g) R. Robiette, V. K. Aggarwal,
J. N. Harvey, J. Am. Chem. Soc. 2007, 129, 15513; h) L. S. Santos,
Eur. J. Org. Chem. 2008, 235; i) G. W. Amarante, H. M. S.
Milagre, B. G. Vaz, B. R. V. Ferreira, M. N. Eberlin, F. Coelho, J.
Org. Chem. 2009, 74, 3031; j) F. Maseras, M. N. Eberlin, F.
Coelho, Chem. Eur. J. 2009, 15, 12460; k) D. Roy, C. Patel, R. B.
Sunoj, J. Org. Chem. 2009, 74, 6936; l) L. Dong, S. Qin, Z. Su, H.
Yang, C. Hu, Org. Biomol. Chem. 2010, 8, 3985.
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Asymmetric Catalysis
S. Takizawa, T. M.-N. Nguyen,
A. Grossmann, D. Enders,
H. Sasai*
&&&& — &&&&
Enantioselective Synthesis of a-
Alkylidene-g-Butyrolactones:
Intramolecular Rauhut–Currier Reaction
Promoted by Acid/Base Organocatalysts
Teaming up: The title reaction has been
developed to deliver the product a-alky-
lidene-g-butyrolactones as single diaste-
reomers with up to 98% ee (see scheme;
Ts =4-toluenesulfonyl). The enantio-
selective process is catalyzed by 1, which
contains both Lewis base and Brønsted
acid moieties.
Angew. Chem. Int. Ed. 2012, 51, 1 – 5
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