Enzyme- and Ruthenium-Catalyzed Enantioselective Transformation of α-Allenic Alcohols into 2,3-Dihydrofurans

Article abstract of DOI:10.1002/anie.201601505

An efficient one-pot method for the enzyme- and ruthenium-catalyzed enantioselective transformation of α-allenic alcohols into 2,3-dihydrofurans has been developed. The method involves an enzymatic kinetic resolution and a subsequent ruthenium-catalyzed c

Full text of DOI:10.1002/anie.201601505

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International Edition: DOI: 10.1002/anie.201601505
German Edition: DOI: 10.1002/ange.201601505
Asymmetric Catalysis
Enzyme- and Ruthenium-Catalyzed Enantioselective Transformation
of a-Allenic Alcohols into 2,3-Dihydrofurans
Bin Yang+, Can Zhu+, Youai Qiu, and Jan-E. Bäckvall*
Abstract: An efficient one-pot method for the enzyme- and
ruthenium-catalyzed enantioselective transformation of a-
allenic alcohols into 2,3-dihydrofurans has been developed.
The method involves an enzymatic kinetic resolution and
a subsequent ruthenium-catalyzed cycloisomerization, which
provides 2,3-dihydrofurans with excellent enantioselectivity
(up to > 99% ee). A ruthenium carbene species was proposed
as a key intermediate in the cycloisomerization.
A
llenes, a class of compounds with a unique substructure of
two cumulative carbon–carbon double bonds, have been
proven to be powerful building blocks for the construction of
complicated skeletons.[1,2] Thus, much attention has been
focused on the transition metal-catalyzed cyclization of
allenes[3–5] with a nucleophilic functionality to synthesize
a variety of potentially useful heterocycles.[6–10] For example,
a-allenic alcohols with a stereogenic center provide ready
access to chiral oxocycles. In the past few decades, a number
of methods have been reported for the synthesis of chiral a-
allenic alcohols.[7,10,11] However, these methods either require
stoichiometric chiral reagents or a complicated chiral ligand,
the multiple-step synthesis of which would limit their practical
application. Therefore, new methodologies for efficient
access to optically pure a-allenic alcohols with broad com-
patibility and excellent enantioselectivity are still highly
desired.
Figure 1. Kazlauskas rule for the enzymatic kinetic resolution of
secondary alcohols.
enzymatic kinetic resolution of chiral a-allenic alcohols is still
a
problem.[14] Furthermore, dynamic kinetic resolution
(DKR), which could overcome the theoretical maximum
yield of 50% of KR, would enable the desired enantiomer to
be obtained in up to 100% yield by coupling of the KR with
a suitable racemization reaction (Scheme 1).[15] However, we
were surprised to find that the racemization catalyst C1
(Scheme 2) did not racemize allenic alcohols, but instead
promoted their cyclization in an unexpected way. On the basis
of this observation, we developed a one-pot process for the
enantioselective synthesis of 2-substituted 2,3-dihydrofurans
with the highest ee values observed for these compounds
among all existing methods.
Enzymatic kinetic resolution (KR)[12] of racemates is an
efficient and powerful method to produce enantiomerically
enriched compounds.[13a] Enzymatic KR would give excellent
enantioselectivity for those substrates that conform to the
Kazlauskas rule[13b] (Figure 1a), such as aryl-substituted
propargylic alcohols (Figure 1b). However, enzymatic trans-
formations of a-allenic alcohols are still challenging, as the
allene unit did not fit well as the medium-sized group into the
active site of typical lipases, thus leading to low enantio-
selectivity (Figure 1c).[11] Therefore, synthetically efficient
We screened a series of biocatalysts for the enantioselec-
tive transacylation of allenic alcohols 1 in organic solvents
(for details, see Table S1 in the Supporting Information).
CALA gave relatively low enantioselectivity and a low
[*] B. Yang,[+] Dr. C. Zhu,[+] Dr. Y. Qiu, Prof. Dr. J.-E. Bäckvall
Department of Organic Chemistry, Arrhenius Laboratory
Stockholm University
10691 Stockholm (Sweden)
E-mail: jeb@organ.su.se
[+] These authors contributed equally to this work.
Supporting information for this article can be found under:
http://dx.doi.org/10.1002/anie.201601505.
ꢀ 2016 The Authors. Published by Wiley-VCH Verlag GmbH & Co.
KGaA. This is an open access article under the terms of the Creative
Commons Attribution Non-Commercial NoDerivs License, which
permits use and distribution in any medium, provided the original
work is properly cited, the use is non-commercial, and no
modifications or adaptations are made.
Scheme 1. Envisioned dynamic kinetic resolution (DKR) of a-allenic
alcohols and observed outcome.
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Table 1: Ruthenium-catalyzed cycloisomerization of (rac)-1.[a]
reaction rate. By control of the reaction time and temperature
with substrate 1a, the CALB family (CALB wild type and
a CALB mutant[16]) afforded moderate E values (ranging
from 32 to 44 depending on the variant and the solid support).
To our delight, lipase PS on different solid supports displayed
excellent enantioselectivity; IL1-PS (IL1-supported lipase
PS) showed the best enantioselectivity and highest reaction
rate. After this preliminary screening (see Table S1) we next
investigated the substrate scope for the enzymatic kinetic
resolution under the optimal reaction conditions. Although
the E values were low for the two starting materials (rac)-1c
and (rac)-1l (with 2-methoxyphenyl and cyclohexyl R sub-
stituents), probably owing to steric hindrance, IL1-PS showed
excellent enantioselectivity for a wide range of substrates, in
which the allene was tolerated as the medium-sized group
(see Table S2). The calculated E values for these substrates
ranged from 100 to 780.
Entry
R
t [h]
Yield of 2 [%][b]
1
2
3
4
5
6
7
8
9
Ph
1.5
1.5
1.5
1.5
1.5
2
2
2
4
4
83 ((rac)-2a)
85 ((rac)-2b)
88 ((rac)-2c)
91 ((rac)-2d)
77 ((rac)-2e)
93 ((rac)-2 f)
92 ((rac)-2g)
84 ((rac)-2h)
85 ((rac)-2i)
95 ((rac)-2j)
90 ((rac)-2k)
90 ((rac)-2l)
4-Me-C6H4
2-MeO-C6H4
3-MeO-C6H4
4-MeO-C6H4
4-Br-C6H4
4-Cl-C6H4
4-F-C6H4
4-CF3-C6H4
2-Np
10
11
12
Bn
cyclohexyl
1.5
1.5
[a] The starting alcohol (rac)-1 (0.5 mmol) was dissolved toluene (1 mL)
in the presence of the Shvo catalyst C1 (2 mol%). [b] Yield of the isolated
product. Bn=benzyl, Np=naphthyl.
With a high E value, both the allenic alcohol and the
allenic acetate can be obtained with high ee values in the KR.
The KR of (rac)-1 f under optimal conditions gave (S)-1 f with
99.9% ee in 43% yield and (R)-3 f with 95.2% ee in 47%
yield within 8 h [Eq. (1)].
We next set out to optimize the reaction conditions for the
ruthenium-catalyzed cyclization with C1 by using (rac)-1a as
the substrate (for details, see Table S3). Toluene, THF, DCE,
acetone, dioxane, MeOH, and MeCN were tested as the
solvent, and all gave (rac)-2a as a single product. The best
result was found with toluene, which afforded (rac)-2a in
83% yield (Table 1, entry 1). The reaction still proceeded well
with a catalyst loading of 2 mol%.
Under the optimal reaction conditions, we next inves-
tigated the scope of the cycloisomerization of allenic alcohols
(rac)-1. A range of substituted 1-aryl buta-2,3-dien-1-ols were
examined: Derivatives substituted with p-Me, o-MeO, m-
MeO, p-MeO, p-Br, p-Cl, and p-F groups all reacted smoothly
to afford the corresponding products (rac)-2b–h as the only
product in excellent yields (Table 1, entries 2–8). However,
substrates bearing an electron-deficient substituent, such as p-
CF3 (substrate (rac)-1i) and 2-naphthyl (substrate (rac)-1j),
required a longer reaction time (4 h vs. 1.5 h; Table 1,
entries 9 and 10). The cycloisomerization reaction also
proceeded well to give 2k and 2l in excellent yields when
the R substituent was an alkyl group, such as benzyl (substrate
(rac)-1k) or cyclohexyl (substrate (rac)-1l).
Having established this highly enantioselective KR
method, we attempted to develop a DKR method by
combining the KR with the Shvo catalyst (C1).[17,18] On the
basis of previous research within our research group on the
dynamic kinetic resolution (DKR)[15] of secondary alcohols, in
which biocatalysts are combined with a transition-metal
catalyst, we tested racemization catalysts C1 and C2
(Scheme 2) with 1-phenylbuta-2,3-dien-1-ol ((rac)-1a) as the
We next studied the cyclization of optically pure (S)-1a.
Since catalyst C1 is utilized as a racemization catalyst in the
DKR of secondary alcohols and primary amines, a drop in the
ee value may occur during the cyclization. When optically
pure (S)-1a (obtained by KR with IL1-PS) was treated with
catalyst C1 (5 mol%) at 708C for 16 h, (S)-2a was obtained
with 97.3% ee [Eq. (2)]. This result indicates that the cyclo-
isomerization is about two orders of magnitude faster than
racemization, which means that the configuration of the
Scheme 2. Ruthenium-based racemization catalysts.
standard substrate. When (rac)-1a was treated with catalyst
C1, isopropenyl acetate, and IL1-PS in the presence of
Na2CO3 in toluene at 708C overnight, the desired product was
not observed. Surprisingly, the cyclized product 2a (see
Table 1) was obtained in 83% yield as a single product. In
contrast, catalyst C2 was inactive toward the allenic alcohol
(rac)-1a.
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can be isolated from its diastereomers, was produced in 65%
yield without loss of optical purity (97.5% ee). Compound 4
can be used in the synthesis of optically pure (À)-3-
deoxyisoaltholactone, the enantiomer of a natural product,
by an existing method.[19]
We further studied the mechanism of this ruthenium-
catalyzed cycloisomerization. It was first investigated whether
2,5-dihydrofuran 5 could be an intermediate in this reaction
(Scheme 5). Compound 5, synthesized by a known method,[20]
Scheme 5. Reaction to test whether 5 could be an intermediate in the
ruthenium-catalyzed reaction.
Scheme 3. Scope of the KR/cycloisomerization one-pot reaction. A
solution of (rac)-1 (0.5 mmol) in dry toluene (1 mL) was mixed with
IL1-PS (10.0 mg) and dry Na2CO3 (26.3 mg) in a reaction vial, and the
resulting mixture was stirred for 5 min. Isopropenyl acetate (110 mL,
1 mmol, 2 equiv) was then added, and the reaction mixture was stirred
at 508C. After 12–16 h, the Shvo catalyst C1 (2 mol%) was added to
the solution, and stirring was continued for another 4 h at 708C. The
ee values of the products were determined by GC analysis on a chiral
stationary phase (see the Supporting Information for details).
was heated to 708C for 4 h in the presence of catalyst C1
(2 mol%) in toluene. Surprisingly, instead of 2 f, an unsatu-
rated ketone 6 was formed in quantitative yield. This
observation suggests that 5 is not an intermediate in the
catalytic cycle.
In an effort to gain deeper insight into the reaction
mechanism, we performed deuterium-labeling experiments.
The reaction was carried out with [D1]1 f as the starting
material in the presence of catalyst C1 (2 mol%) in toluene at
708C for 2 h (Scheme 6a). Compound 2 fa was formed with
stereogenic center will be maintained in the C1-catalyzed
cyclization.
With these results in hand, we designed an enantioselec-
tive one-pot synthesis of 2,3-dihydrofurans by combining the
enzymatic kinetic resolution with C1-catalyzed cycloisomeri-
zation (Scheme 3). To our delight, for substrates with good
E values in KR, the cycloisomerization products (S)-2 were
obtained in 37–45% yield with excellent asymmetric induc-
tion (97.5–99.9% ee). Furthermore, even substrate (rac)-1c,
which underwent slow KR with low selectivity, was converted
into (S)-2c in 29% yield with 99.6% ee with a longer reaction
time.
To demonstrate the synthetic utility of the products, we
conducted an epoxide-formation–opening reaction to intro-
duce two new chiral centers (Scheme 4). Compound 4, which
Scheme 4. Formal synthesis of (À)-3-deoxyisoaltholactone from
(S)-2a. mCPBA=m-chloroperbenzoic acid.
Scheme 6. Transformation of deuterium-labeled allenic alcohols.
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full conversion with a combined amount of 0.7 deuterium
In conclusion, we have developed a novel synthesis of 2-
atoms in the position of the two allylic hydrogen atoms X1 +
X2 and 19% deuterium incorporation at the vinylic position
X3. A cyclization reaction of [D2]1 f was carried out under the
same reaction conditions to give 2 fb. To our surprise, a very
similar deuterium distribution at the allylic position (X1 + X2)
and vinylic position X3 was observed (Scheme 6b). The only
difference was that instead of 0% deuterium incorporation at
the vinylic position X4 as in 2 fa, 100% deuterium incorpo-
ration was found at the X4 position of 2 fb. The reaction of
[D3]1 f (Scheme 6c) afforded product 2 fc, which had about
twice the amount of deuterium in positions X1 + X2 and X3 as
compared to the previous products 2 fa and 2 fb.
substituted 2,3-dihydrofurans from readily available allenic
alcohols through a ruthenium-catalyzed cycloisomerization.
On the basis of this transformation, a one-pot enantioselec-
tive process combining KR and cycloisomerization was
established. Oxygen-containing heterocycles were synthe-
sized under mild reaction conditions with good functional-
group tolerance. The products obtained can be further
transformed into a variety of important derivatives. This
method should be attractive for the pharmaceutical industry.
A ruthenium carbene int-4 is proposed as a key intermediate
of the cyclization.
On the basis of the deuterium-labeling experiments, we
propose a possible mechanism for the cycloisomerization of
substituted 2,3-allen-1-ols (Scheme 7; see Scheme S2 in the
Acknowledgments
Financial support from the European Research Council
(ERC AdG 247014), the Swedish Research Council (621-
2013-4653), the Berzelii Center EXSELENT, and the Knut
and Alice Wallenberg Foundation is gratefully acknowledged.
Keywords: allenic alcohols · asymmetric catalysis ·
cycloisomerization · kinetic resolution · ruthenium
How to cite: Angew. Chem. Int. Ed. 2016, 55, 5568–5572
Angew. Chem. 2016, 128, 5658–5662
[1] a) H. F. Schuster, G. M. Coppola, Allenes in Organic Synthesis,
Wiley, New York, 1984; b) S. Patai, The Chemistry of Ketenes,
Allenes, and Related Compounds, Part 1, Wiley, New York, 1980.
[2] For reviews, see: a) C. S. Adams, C. D. Weatherly, E. G. Burke,
J. M. Schomaker, Chem. Soc. Rev. 2014, 43, 3136; b) T. Lechel, F.
Pfrengle, H.-U. Reissig, R. Zimmer, ChemCatChem 2013, 5,
2100; c) R. Zimmer, C. U. Dinesh, E. Nandanan, F. A. Khan,
Chem. Rev. 2000, 100, 3067; d) J. A. Marshall, Chem. Rev. 2000,
100, 3163; e) X. Lu, C. Zhang, Z. Xu, Acc. Chem. Res. 2001, 34,
535; f) R. W. Bates, V. Satcharoen, Chem. Soc. Rev. 2002, 31, 12;
g) J. Ye, S. Ma, Org. Chem. Front. 2014, 1, 1210; h) L.-L. Wei, H.
Xiong, R. P. Hsung, Acc. Chem. Res. 2003, 36, 773; i) P. Rivera-
Fuentes, F. Diederich, Angew. Chem. Int. Ed. 2012, 51, 2818;
Angew. Chem. 2012, 124, 2872; j) S. Ma, Acc. Chem. Res. 2009,
42, 1679; k) B. Alcaide, P. Almendros, C. Aragoncillo, Chem.
Soc. Rev. 2010, 39, 783; l) S. Ma, Aldrichimica Acta 2007, 40, 91;
m) M. Jeganmohan, C.-H. Cheng, Chem. Commun. 2008, 3101;
n) A. S. K. Hashmi, Angew. Chem. Int. Ed. 2000, 39, 3590;
Angew. Chem. 2000, 112, 3737; o) L. K. Sydnes, Chem. Rev. 2003,
103, 1133; p) A. Hoffmann-Rçder, N. Krause, Angew. Chem. Int.
Ed. 2002, 41, 2933; Angew. Chem. 2002, 114, 3057; q) C. Aubert,
L. Fensterbank, P. Garcia, M. Malacria, A. Simonneau, Chem.
Rev. 2011, 111, 1954; r) N. Krause, C. Winter, Chem. Rev. 2011,
111, 1994; s) F. López, J. L. MascareÇas, Chem. Eur. J. 2011, 17,
418; t) S. Yu, S. Ma, Angew. Chem. Int. Ed. 2012, 51, 3074;
Angew. Chem. 2012, 124, 3128; u) S. Yu, S. Ma, Chem. Commun.
2011, 47, 5384; v) S. Ma, Acc. Chem. Res. 2003, 36, 701; w) J. Ye,
S. Ma, Acc. Chem. Res. 2014, 47, 989; x) S. Ma, Chem. Rev. 2005,
105, 2829.
Scheme 7. Proposed mechanism for the ruthenium-catalyzed cycloiso-
merization of allenic alcohols. For monomeric [Ru] and [Ru]À species,
see the Supporting Information.
Supporting Information for details about the nature of the
metal complexes involved). Catalyst C1 is known to split into
two monomeric species on heating in solution (see the
=
Supporting Information). Coordination of the terminal C C
bond of 1 to Ru would form int-1, and subsequent ring closure
of int-1 would give a vinyl–ruthenium intermediate int-2.
Rearrangement of int-2 would give the key intermediate
ruthenium carbene int-3. Protonation of int-3 to give int-4 and
subsequent deprotonation at the CH2O position would
produce int-5. The reaction of int-4 to give int-5 is believed
to be irreversible, since the cyclization of [D2]1 f to 2 fb
(Scheme 6b) led to 100% deuterium incorporation at the
vinylic position X4. The equilibrium between int-4 and int-3
will lead to the observed deuterium content in the allylic
(X1 + X2) position of the product, which reflects the D+/H+
ratio in the solvent.[21] The much lower deuterium content in
the vinylic position X3 is due to a kinetic isotope effect (kH/kD)
in the protonation of int-5, since this step is irreversible.
[3] For Ag, see: M. Harmata, Silver in Organic Chemistry, Wiley,
New York, 2010.
[4] For Pd, see: a) J. Piera, K. Närhi, J.-E. Bäckvall, Angew. Chem.
Int. Ed. 2006, 45, 6914; Angew. Chem. 2006, 118, 7068;
b) A. K. Š. Persson, J.-E. Bäckvall, Angew. Chem. Int. Ed.
2010, 49, 4624; Angew. Chem. 2010, 122, 4728; c) Y. Deng, T.
Bartholomeyzik, J.-E. Bäckvall, Angew. Chem. Int. Ed. 2013, 52,
6283; Angew. Chem. 2013, 125, 6403; d) C. Zhu, B. Yang, T.
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Jiang, J.-E. Bäckvall, Angew. Chem. Int. Ed. 2015, 54, 9066;
Angew. Chem. 2015, 127, 9194; e) C. Zhu, X. Zhang, X. Lian, S.
Ma, Angew. Chem. Int. Ed. 2012, 51, 7817; Angew. Chem. 2012,
124, 7937; f) C. Zhu, S. Ma, Org. Lett. 2013, 15, 2782; g) C. Zhu,
S. Ma, Org. Lett. 2014, 16, 1542; h) C. Zhu, S. Ma, Adv. Synth.
Catal. 2014, 356, 3897; i) C. Zhu, S. Ma, Angew. Chem. Int. Ed.
2014, 53, 13532; Angew. Chem. 2014, 126, 13750; j) C. Zhu, B.
Yang, J.-E. Bäckvall, J. Am. Chem. Soc. 2015, 137, 11868; k) C.
Zhu, B. Yang, Y. Qiu, J.-E. Bäckvall, Chem. Eur. J. 2016, 22, 2939.
[5] For Au, see: a) D. J. Gorin, F. D. Toste, Nature 2007, 446, 395;
b) Y. Qiu, D. Ma, C. Fu, S. Ma, Tetrahedron 2013, 69, 6305; c) Y.
Qiu, J. Zhou, J. Li, C. Fu, Y. Guo, H. Wang, S. Ma, Chem. Eur. J.
2015, 21, 15939.
[6] S. Ma, S. Zhao, J. Am. Chem. Soc. 1999, 121, 7943.
[7] a) Y. Wang, K. Zhang, R. Hong, J. Am. Chem. Soc. 2012, 134,
4096; b) S. Ma, W. Gao, J. Org. Chem. 2002, 67, 6104.
[8] a) E. Yoneda, T. Kaneko, S. Zhang, K. Onitsuka, S. Takahashi,
Org. Lett. 2000, 2, 441; b) E. Yoneda, S. Zhang, D. Zhao, K.
Onitsuka, S. Takahashi, J. Org. Chem. 2003, 68, 8571.
[9] A. S. Dudnik, A. W. Sromek, M. Rubina, J. T. Kim, A. V. Kelꢀin,
V. Gevorgyan, J. Am. Chem. Soc. 2008, 130, 1440.
[10] a) G. P. Boldrini, L. Lodi, E. Tagliavini, C. Tarasco, C. Trombini,
A. Umani-Ronchi, J. Org. Chem. 1987, 52, 5447; b) E. J. Corey,
C.-M. Yu, D.-H. Lee, J. Am. Chem. Soc. 1990, 112, 878; c) H. C.
Brown, U. R. Khire, G. J. Narla, Org. Chem. 1995, 60, 8130;
d) K. Iseki, Y. Kuroki, Y. Kobayashi, Tetrahedron: Asymmetry
1998, 9, 2889; e) M. Nakajima, M. Saito, S. Hashimoto,
Tetrahedron: Asymmetry 2002, 13, 2449; f) C.-M. Yu, S.-K.
Yoon, K. Baek, J.-Y. Lee, Angew. Chem. Int. Ed. 1998, 37, 2392;
Angew. Chem. 1998, 110, 2504; g) M. Inoue, M. Nakada, Angew.
Chem. Int. Ed. 2006, 45, 252; Angew. Chem. 2006, 118, 258; h) G.
Xia, H. Yamamoto, J. Am. Chem. Soc. 2007, 129, 496.
[11] D. Xu, Z. Li, S. Ma, Chin. J. Org. Chem. 2004, 22, 310.
[12] M. Breuer, K. Ditrich, T. Habicher, B. Hauer, M. Kesseler, R.
Stürmer, T. Zelinski, Angew. Chem. Int. Ed. 2004, 43, 788;
Angew. Chem. 2004, 116, 806.
[13] a) U. T. Bornscheuer, R. J. Kazlauskas in Hydrolases in Organic
Synthesis: Regio- and Stereoselective Biotransformations, 1st ed.,
Wiley-VCH, Weinheim, 1999, pp. 65 – 129; b) R. J. Kazlauskas,
A. Weissfloh, A. T. Rappaport, J. Org. Chem. 1991, 56, 2656.
[14] After the completion of this study, a KR of allenic alcohols was
reported that gave good enantioselectivity in 1 – 5 days: W. Li, Z.
Lin, L. Chen, X. Tian, Y. Wang, S.-H Huang, R. Hong,
Tetrahedron Lett. 2016, 57, 603.
[15] O. Verho, J.-E. Bäckvall, J. Am. Chem. Soc. 2015, 137, 3996.
[16] B. Yang, R. Lihammar, J.-E. Bäckvall, Chem. Eur. J. 2014, 20,
13517.
[17] a) Y. Blum, Y. Shvo, Isr. J. Chem. 1984, 24, 144; b) Y. Shvo, D.
Czarkie, Y. Rahamim, D. F. Chodosh, J. Am. Chem. Soc. 1986,
108, 7400.
[18] a) R. Karvembu, R. Prabhakaran, K. Natarajan, Coord. Chem.
Rev. 2005, 249, 911; b) B. L. Conley, M. K. Pennington-Boggio,
E. Boz, T. J. Williams, Chem. Rev. 2010, 110, 2294; c) J. S. M.
Samec, J. E. Bäckvall, Encyclopedia of Reagents for Organic
Synthesis, 2nd ed., Wiley Interscience, 2009.
[19] S. P. Fearnley, P. Lory, Tetrahedron Lett. 2014, 55, 5207.
[20] G. Leandri, H. Monti, M. Bertrand, Tetrahedron 1974, 30, 289.
[21] The protonation of int-3 is reversible and therefore there will be
only an equilibrium deuterium isotope effect, which is very
small.
Received: February 11, 2016
Published online: March 23, 2016
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