Gold-Catalyzed Tandem Cycloisomerization-Halogenation of Chiral Homopropargyl Sulfonamides

Article abstract of DOI:10.1002/chem.201503891

Two new gold-catalyzed tandem cycloisomerization-halogenation reactions of chiral homopropargyl sulfonamides have been developed. Various enantioenriched 3,3-diiodopyrrolidin-2-ols and 3-fluoropyrrolidin-2-ols were obtained in moderate-to-good yields with excellent enantio- and diastereoselectivity.

Full text of DOI:10.1002/chem.201503891

DOI: 10.1002/chem.201503891
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Gold Catalysis |Hot Paper|
Gold-Catalyzed Tandem Cycloisomerization–Halogenation of
Chiral Homopropargyl Sulfonamides
Chao Shu,[a] Long Li,[a] Cang-Hai Shen,[a] Peng-Peng Ruan,[a] Chao-Yue Liu,[a] and
Long-Wu Ye*[a, b]
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Abstract: Two new gold-catalyzed tandem cycloisomeriza-
tion–halogenation reactions of chiral homopropargyl sulfo-
namides have been developed. Various enantioenriched 3,3-
diiodopyrrolidin-2-ols and 3-fluoropyrrolidin-2-ols were ob-
tained in moderate-to-good yields with excellent enantio-
and diastereoselectivity.
Introduction
Organic halides are highly useful and valuable compounds
that can be found in a large number of biologically active nat-
ural products and pharmaceutical agents.[1] In addition, they
can also serve as versatile substrates for various synthetic
transformations.[2] As a result, a range of halogenation reac-
tions have been developed to prepare these compounds,
mainly by treating substrates with elemental halogen species
or by adding reagents such as N-iodo- (NIS), N-bromo- (NBS),
or N-chlorosuccinimide (NCS).[3] However, these reactions suffer
from limited substrate scope, harsh reaction conditions, com-
petitive side reactions, and low yields. In particular, there is
a lack of efficient synthetic methods for the enantioselective
synthesis of halogenated products.[4] Therefore, the exploration
of novel approaches to halogenation that have high enantiose-
lectivity, flexibility, and good modularity is highly desirable.
Homogeneous gold catalysis has received extensive atten-
tion over the past decade, and it has enabled facile synthesis
of an incredible variety of complicated skeletons from readily
available starting materials under relatively mild reaction con-
ditions.[5,6] Our interest in this field is focused on the explora-
tion of gold-catalyzed tandem reactions and their applications
in diversity-based organic synthesis.[7] In our recent study on
gold-catalyzed cycloisomerization-initiated tandem reactions,[8]
we reported the facile and practical construction of a series of
heterocycle skeletons from readily available chiral homopro-
pargyl sulfonamides by combining chiral tert-butylsulfinimine
chemistry and gold catalysis (Scheme 1).[8a–c] Herein, we de-
scribe two novel gold-catalyzed tandem 5-endo-dig cycloiso-
merization–halogenation reactions of chiral homopropargyl
sulfonamides that use either NIS or 1-chloromethyl-4-fluoro-
1,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate) (Select-
fluor) as the halogen source and the efficient formation of vari-
ous enantioenriched 3,3-diiodopyrrolidin-2-ols 2 and 3-fluoro-
pyrrolidin-2-ols 3. Importantly, excellent diastereocontrol was
achieved in both transformations.
Scheme 1. Gold-catalyzed 5-endo-dig cycloisomerization-initiated tandem re-
actions based on chiral homopropargyl sulfonamides. PG=protecting
group; m-CPBA=meta-chloroperbenzoic acid.
Results and Discussion
Very recently, we demonstrated an efficient gold-catalyzed
anti-Markovnikov hydroamination of chiral homopropargyl sul-
fonamides that led to enantioenriched 2,3-dihydropyrroles in
excellent yields.[8a] Inspired by this result, we envisioned that
vinyl-gold intermediate A might be further trapped by electro-
philic NIS to afford the corresponding 4-iodo-2,3-dihydropyr-
role.[9] Surprisingly, when substrate 1a was treated with NIS
(1.2 equiv) under the previously optimized reaction conditions
3,3-diiodopyrrolidin-2-ol 2a was isolated in 36% yield, instead
of the anticipated product 2a’ (Scheme 2).[10,11] Notably, excel-
Scheme 2. Ts =para-toluenesulfonyl, Tf=trifluoromethanesulfonyl,
DCE=1,2-dichloroethane.
lent cis diastereoselectivity was achieved in this transformation.
We then set out to screen different conditions for this reac-
tion by using homopropargyl sulfonamide 1a as a model sub-
strate. Considering that two iodine atoms were introduced
during this process, we used NIS (2.1 equiv) to optimize the re-
action conditions. The influence of different gold catalysts with
a range of electronic and steric characteristics was investigated
first (Table 1, entries 1–7). [BrettPhosAuNTf2] showed the best
catalytic activity: the desired 3,3-diiodopyrrolidin-2-ol 2a was
obtained in 52% yield, albeit with a small amount of pyrroli-
dine byproduct 2aa, which was formed by gold-catalyzed
tandem cycloisomerization–dimerization of 1a (Table 1,
entry 6).[8b] Notably, in the absence of any gold catalyst none
[a] C. Shu, L. Li, C.-H. Shen, P.-P. Ruan, C.-Y. Liu, Prof. Dr. L.-W. Ye
State Key Laboratory of Physical Chemistry of Solid Surfaces and
The Key Laboratory for Chemical Biology of Fujian Province
College of Chemistry and Chemical Engineering
Xiamen University, Xiamen, 361005, Fujian (P. R. China)
E-mail: longwuye@xmu.edu.cn
[b] Prof. Dr. L.-W. Ye
State Key Laboratory of Organometallic Chemistry
Shanghai Institute of Organic Chemistry
Chinese Academy of Sciences, Shanghai 200032 (P. R. China)
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/chem.201503891.
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Table 1. Optimization of the reaction conditions.[a]
Table 2. (Continued)
Entry Substrate
1
Product
2
Yield
[%]
Entry
Metal catalyst
Additive [mol%]
Yield [%][b]
2a
2aa
4
5
6
1d
1e
1 f
2d 66
1
2[c]
3[c]
4
5
6
7[c]
8[c]
9[e]
10
11
12[f]
[Me3PAuNTf2]
[IPrAuNTf2]
[Ph3PAuNTf2]
[(ArO)3PAuNTf2][d]
[XPhosAuNTf2]
[BrettPhosAuNTf2]
[(4-CF3C6H4)3PAuNTf2]
AgNTf2
–
–
–
–
–
–
–
–
14
3
<1
<1
7
8
6
<1
<1
<1
<1
<1
<1
<5
<5
12
16
52
<5
<1
<1
69
30
68
2e 75
2 f 64
2g 69
–
–
[BrettPhosAuNTf2]
[BrettPhosAuNTf2]
[BrettPhosAuNTf2]
Et3N (2)
Et3N (5)
Et3N (2)
7
8
1g
1h
1i
[a] Reactions run in vials without exclusion of air or moisture; [1a]=
0.05m. [b] Estimated by 1H NMR spectroscopy by using diethyl phthalate
as internal reference. [c] Compound 2a was consumed but the reaction
gave a complicated mixture of products. [d] Ar=2,4-di-tert-butylphenyl.
[e] 90% of 1a remained unreacted. [f] The reaction was performed in
a flame-dried vial with dry DCE as the solvent and H2O (2 equiv) as an ad-
ditive.
2h 65
9
2i
2j
72
70
of the desired product 2a was formed (Table 1, entry 9).
AgNTf2 did not catalyze this transformation (Table 1, entry 8).
To our delight, the use of Et3N (2 mol%) minimized the forma-
tion of pyrrolidine 3a and led to the formation of 2a in 69%
yield (Table 1, entry 10); a similar result was obtained in the
presence of water (2 equiv) (Table 1, entry 12).[12] However, the
yield of 2a decreased significantly with an increased loading of
Et3N (Table 1, entry 11).
10
11
1j
1k
2k 73
With the optimized reaction conditions in hand, the scope
of this tandem reaction was explored (Table 2). A series of
12
13
14
1l
2l
72
Table 2. Reaction scope for the formation of 3,3-diiodopyrrolidin-2-ols
2.[a]
1m
1n
2m 60
2n 64
Entry Substrate
1
Product
2
Yield
[%]
[a] Reactions run in vials without exclusion of air or moisture; [1]=
0.05m; isolated yields are reported. [b] 99% ee, determined by HPLC on
a chiral stationary phase.
1[b]
1a
1b
1c
2a 63
2b 66
2c 68
chiral homopropargyl amides 1 (easily prepared by using Ell-
man’s tert-butylsulfinimine chemistry)[13] were suitable sub-
strates for this transformation, and the corresponding 3,3-diio-
dopyrrolidin-2-ols 2 were obtained in moderate-to-good yields.
A range of functional groups were also well tolerated, includ-
ing phenyl (Table 2, entry 3), protected hydroxy (Table 2,
entry 4), and N-phthaloyl groups (Table 2, entry 5). Aromatic
substrates bearing para-substituted electron-donating or elec-
2
3
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tron-withdrawing substituents (e.g., F, Cl, Br, Me, and OMe) on
the phenyl ring also worked well in the reaction to smoothly
yield the desired products (Table 2, entries 6–9, 11, and 12).
Moreover, even the sterically hindered substrate 1j was com-
patible with this transformation (Table 2, entry 10). Changing
the N-protecting group from N-tosyl (Ts) to N-mesyl (Ms) had
a slight effect on the reaction: 2m was formed in 60% yield
(Table 2, entry 13). Notably, with (S)-(+)-tert-butylsulfinimide-
derived homopropargyl amide 1n instead of (R)-(+)-tert-butyl-
sulfinimide-derived 1a as the substrate, the reaction proceed-
ed smoothly to afford the desired product 2n in 64% yield
with the opposite enantioselectivity to 2a (Table 2, entry 14).
In these transformations, the enantiomeric excess (ee) was well
maintained; we determined the ee of 2a as a representative
example (Table 2, entry 1). Importantly, excellent cis diastereo-
selectivity (diastereomeric ratio (d.r.)>50:1, determined by
Table 3. Reaction scope for the formation of 3-fluoropyrrolidin-2-ols 3.[a]
Entry Substrate
1
Product
3
Yield
[%]
1
1a
1b
1d
1 f
3a 61
3b 54
3c 61
3d 55
2
3
1
crude H NMR spectroscopy) was achieved in all cases. The mo-
lecular structure of 2g was further confirmed by X-ray crystal-
lography (Figure 1).[14] Thus, this protocol provides a highly effi-
4[b]
5
6
7
8
1h
1i
3e 56
3 f 60
3g 71
3h 62
1k
1l
[a] Reactions run in vials without exclusion of air and moisture; [1]=
0.05m; isolated yields are reported. [b] 99% ee, determined by HPLC on
a chiral stationary phase.
Figure 1. X-ray structure of 2g.
cient and practical route to prepare both enantiomers of 3,3-
diiodopyrrolidin-2-ols 2 by simply adjusting the starting chiral
source. Our attempts to extend the reaction to tert-butylsulfo-
nylamide 1o, tert-butylsulfinylamide 1p, 5-amino-1-yne 1q,
and internal alkyne 1r[15] only resulted in the formation of in-
separable mixtures.
Attempts to expand this chemistry to a tandem cycloisome-
rization–bromination sequence have been unsuccessful as yet.
However, interestingly, the reaction gave the corresponding
monofluorinated pyrrolidin-2-ols 3 by using Selectfluor as the
fluorination reagent. As shown in Table 3, treatment of chiral
homopropargyl amides 1 with Selectfluor (2.1 equiv) in the
presence of [BrettPhosAuNTf2] (5 mol%) and Et3N (2 mol%)
produced 3-fluoropyrrolidin-2-ols 3a–3h in 54–71% yield with
excellent diastereoselectivities (d.r.>10:1, determined by crude
Figure 2. X-ray structure of 3d.
1H NMR spectroscopy). Compound 3d was further character-
ized by X-ray crystallography (Figure 2).[14]
Pyrrolidin-2-ols 3 are potentially useful in organic synthesis
and are valuable precursors for the preparation of important
enantioenriched heterocycles. For example, 3,3-diiodopyrroli-
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din-2-ol 2a was diastereoselectively transformed into the cor-
responding azetidine 4a (73%, d.r.>10:1) without detriment
to the ee. The reaction was initiated by a Horner–Wadsworth–
Emmons olefination, which was followed by a formal NÀH in-
sertion into a carbene derived from the diiodo moiety
(Scheme 3). Furthermore, enantioenriched pyrrolidine 5a was
readily synthesized with high diastereoselectivity (d.r.>10:1)
by a Horner–Wadsworth–Emmons olefination of 3a and a sub-
sequent aza-Michael reaction (Scheme 3).[16]
Conclusion
We have developed an unexpected gold-catalyzed tandem cy-
cloisomerization–diiodination of chiral homopropargyl sulfona-
mides, which allows the efficient synthesis of highly functional-
ized enantioenriched 3,3-diiodopyrrolidin-2-ols, and thus
makes it possible to realize an alkyne tetrafunctionalization
with high diastereoselectivity. Moreover, gold-catalyzed
tandem cycloisomerization–fluorination was also been ach-
ieved with moderate-to-good yields and excellent enantio- and
diastereo-control. The use of readily available substrates,
a simple procedure, and mild reaction conditions (in particular,
no requirement to exclude moisture or air) render this method
potentially useful in organic synthesis. Further investigations
into synthetic applications of the current protocol are in prog-
ress in our laboratory.
Experimental Section
All melting points were determined without correction. 1H NMR
spectra were obtained at 400 or 500 MHz, and 13C NMR spectra
were obtained at 100 or 125 MHz. Spectra were recorded for sam-
ples in solution in CDCl3 or [D6]DMSO, and the residual protonated
solvent signal was used as an internal standard. Coupling con-
stants (J) are given in Hz.
Scheme 3. Synthetic applications.
A plausible reaction pathway to rationalize the formation of
2a and 3a was proposed (Scheme 4).[17] The reaction starts
with formation of the vinyl gold intermediate A by alkyne p
coordination and concomitant 5-endo-dig cyclization.[18] Inter-
General procedure for the preparation of 3,3-diiodopyrroli-
din-2-ols 2
NIS (141.7 mg, 0.63 mmol), Et3N (2.0 mL, 0.003 mmolmLÀ1 in DCE)
and [BrettPhosAuNTf2] (15.3 mg, 0.015 mmol) were added, in this
order, to a solution of homopropargyl amide 1 (0.30 mmol) in DCE
(4.0 mL) at RT. The reaction mixture was stirred at RT, and the reac-
tion progress was monitored by TLC; the reaction typically took
5 h. On completion, the mixture was concentrated under reduced
pressure and the residue was purified by column chromatography
on silica gel (hexanes/ethyl acetate) to afford the desired product
2.
Compound 2a: Oil (111.7 mg, 63%); [a]2D0 =À80.08 (c=1.0 in
CHCl3); 99% ee (HPLC: Chiralpak ASH column; 10:90 iPrOH/hexane;
flow rate=0.6 mLminÀ1; l=200 nm; retention time (tR)=38.96
(major), 32.82 min (minor)); 1H NMR (400 MHz, CDCl3): d=7.83 (d,
J=6.4 Hz, 2H), 7.33 (d, J=6.4 Hz, 2H), 5.73 (d, J=2.4 Hz, 1H),
3.91–3.85 (m, 1H), 3.42 (d, J=2.4 Hz, 1H), 2.94–2.84 (m, 2H), 2.43
(s, 3H), 2.08–1.98 (m, 1H), 1.69–1.61 (m, 1H), 1.32–1.99 (m, 10H),
0.90 ppm (t, J=1.6 Hz, 3H); 13C NMR (100 MHz, CDCl3): d=143.9,
135.9, 129.6, 127.7, 92.9, 61.5, 54.9, 33.8, 31.7, 29.4, 29.1, 25.2, 22.6,
21.6, 14.0, À4.1 ppm; IR (neat): n˜ =3458 (br), 2951, 2926, 2853,
1597, 1468, 1342, 1162, 1028, 814, 680, 582, 548 cmÀ1; MS (ESI): m/
z: 614 [M+Na+]; HRMS: m/z calcd for C18H27I2NNaO3S+: 613.9699
[M+Na+]; found: 613.9693.
Compound 2b: Oil (113.9 mg, 66%); [a]2D0 =À38.08 (c=1.0 in
CHCl3); 1H NMR (400 MHz, [D6]DMSO): d=7.76 (d, J=8.4 Hz, 2H),
7.42 (d, J=5.6 Hz, 1H), 7.39 (d, J=8.0 Hz, 2H), 5.67 (d, J=6.0 Hz,
1H), 3.83–3.77 (m, 1H), 2.66–2.60 (m, 1H), 2.55–2.49 (m, 1H), 2.38
(s, 3H), 1.68–1.62 (m, 2H), 1.52–1.46 (m, 2H), 1.40–1.34 (m, 1H),
1.16–1.02 (m, 2H), 1.01–0.87 (m, 1H), 0.78–0.50 ppm (m, 3H);
13C NMR (125 MHz, CDCl3): d=142.9, 137.8, 129.2, 126.8, 92.4, 64.8,
48.4, 37.2, 29.2, 26.1, 25.8, 25.5, 25.1, 20.9, 3.4 ppm; IR (neat): n˜ =
3470 (br), 2926, 2853, 1594, 1448, 1344, 1162, 1092, 814, 669, 579,
Scheme 4. Plausible mechanism for the formation of 2a and 3a.
mediate A reacts with NIS to provide vinyl iodide B, which is
further converted into the iminium intermediate C in the pres-
ence of another molecule of NIS. Finally, trace water in the re-
action system attacks intermediate C to afford the target prod-
uct 2a. However, in the presence of Selectfluor the reaction
presumably proceeded by the reaction of 2,3-dihydropyrrole D
with Selectfluor; the formation of D was clearly observed by
1H NMR spectroscopy of the reaction mixture.[19] Notably, the
observed cis stereochemistry may be the result of thermody-
namic control, which is also supported by the fact that X-ray
structures of 2g and 3d are consistent with the cis product
being sterically less congested than the alternative trans prod-
uct.
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545 cmÀ1; MS (ESI): m/z: 598 [M+Na+]; HRMS: m/z calcd for
C17H23I2NNaO3S+: 597.9386 [M+Na+]; found: 597.9415.
129.2, 128.5, 127.5, 92.8, 64.0, 58.6, 21.5, À3.5 ppm; IR (neat): n˜ =
3470 (br), 2957, 2917, 2853, 1371, 1661, 1600, 1487, 1347, 1159,
1092, 1036, 814, 671, 585, 545 cmÀ1; MS (ESI): m/z: 626 [M+Na+];
HRMS: m/z calcd for C17H16ClI2NNaO3S+: 625.8526 [M+Na+];
found: 625.8548.
Compound 2c: Oil (121.8 mg, 68%); [a]2D0 =À30.58 (c=1.0 in
1
CHCl3); H NMR (400 MHz, CDCl3): d=7.71 (d, J=8.3 Hz, 2H), 7.30–
7.16 (m, 5H), 7.12 (d, J=7.0 Hz, 2H), 5.71 (s, 1H), 3.89–3.79 (m,
2H), 2.99 (dd, J=14.0, 9.4 Hz, 1H), 2.87 (dd, J=14.0, 6.0 Hz, 1H),
2.71–2.57 (m, 1H), 2.52–2.42 (m, 1H), 2.42–2.32 (m, 4H), 2.10–
1.98 ppm (m, 1H); 13C NMR (100 MHz, CDCl3): d=143.9, 140.7,
135.0, 129.6, 128.4, 128.3, 127.8, 126.0, 92.9, 60.7, 54.7, 34.9, 31.3,
21.5, À4.6 ppm; IR (neat): n˜ =3467 (br), 3024, 2923, 2853, 1597,
Compound 2i: White solid (140.0 mg, 72%); m.p. 163–1658C;
1
[a]2D0 =À38.58 (c=1.0 in CHCl3); H NMR (400 MHz, [D6]DMSO): d=
7.81 (d, J=6.0 Hz, 1H), 7.31 (d, J=8.2 Hz, 2H), 7.26 (d, J=8.4 Hz,
2H), 7.15 (d, J=8.4 Hz, 2H), 7.12 (d, J=8.5 Hz, 2H), 5.75 (d, J=
5.7 Hz, 1H), 4.75 (dd, J=9.4, 6.3 Hz, 1H), 3.11 (dd, J=14.1, 6.3 Hz,
1H), 2.74 (dd, J=14.1, 9.6 Hz, 1H), 2.32 ppm (s, 3H); 13C NMR
(125 MHz, [D6]DMSO): d=143.3, 137.6, 137.3, 131.2, 130.5, 129.4,
127.3, 121.1, 93.2, 63.5, 57.9, 21.4, 1.6 ppm; IR (neat): n˜ =3438 (br),
2956, 2923, 2850, 1593, 1487, 1411, 1344, 1324, 1159, 1041, 1007,
946, 808, 657, 583, 543 cmÀ1; MS (ESI): m/z: 670 [M+Na+]; HRMS:
m/z calcd for C17H16BrI2NNaO3S+: 669.8021 [M+Na+]; found:
669.8048.
1496, 1454, 1339, 1159, 1092, 1025, 812, 753, 671, 579, 548 cmÀ1
;
MS (ESI): m/z: 620 [M+Na+]; HRMS: m/z calcd for C19H21I2NNaO3S+
: 619.9229 [M+Na+]; found: 620.9258.
Compound 2d: Oil (132.5 mg, 66%); [a]2D0 =À65.58 (c=0.5 in
1
CHCl3); H NMR (500 MHz, CDCl3): d=7.80 (d, J=8.2 Hz, 2H), 7.40–
7.27 (m, 7H), 5.69 (s, 1H), 4.49 (s, 2H), 3.91–3.79 (m, 1H), 3.65 (d,
J=7.8 Hz, 1H), 3.43 (t, J=6.5 Hz, 2H), 2.95–2.75 (m, 2H), 2.39 (s,
3H), 2.06–1.96 (m, 1H), 1.70–1.62 (m, 1H), 1.61–1.53 (m, 2H), 1.38–
1.26 (m, 2H), 1.24–1.14 ppm (m, 2H); 13C NMR (100 MHz, CDCl3):
d=143.9, 138.6, 135.8, 129.6, 128.3, 127.7, 127.6, 127.5, 92.9, 72.8,
70.1, 61.4, 54.8, 33.8, 29.5, 26.0, 24.9, 21.6, À4.1 ppm; IR (neat): n˜ =
3461 (br), 2926, 2854, 1597, 1451, 1348, 1163, 1093, 1026, 816, 673,
586, 550 cmÀ1; MS (ESI): m/z: 692 [M+Na+]; HRMS: m/z calcd for
C23H29I2NNaO4S+: 691.9804 [M+Na+]; found: 691.9793.
Compound 2e: Oil (153.0 mg, 75%); [a]2D0 =À64.58 (c=1.0 in
CHCl3); 1H NMR (500 MHz, CDCl3): d=7.87–7.82 (m, 2H), 7.80 (d, J=
8.3 Hz, 2H), 7.74–7.69 (m, 2H), 7.30 (d, J=8.1 Hz, 2H), 5.69 (s, 1H),
3.95–3.87 (m, 2H), 3.72–3.56 (m, 2H), 2.91 (dd, J=14.1, 9.5 Hz, 1H),
2.80 (dd, J=14.1, 6.0 Hz, 1H), 2.41 (s, 3H), 2.08–1.97 (m, 1H), 1.84–
1.74 (m, 1H), 1.71–1.55 ppm (m, 2H); 13C NMR (100 MHz, CDCl3):
d=168.3, 144.0, 135.5, 133.9, 131.9, 129.7, 127.8, 123.2, 92.9, 60.7,
54.3, 37.6, 30.5, 24.1, 21.6, À4.6 ppm; IR (neat): n˜ =3458 (br), 2923,
2856, 1773, 1706 (s), 1440, 1403, 1344, 1159, 1050, 719, 674,
585 cmÀ1; MS (ESI): m/z: 703 [M+Na+]; HRMS: m/z calcd for
C22H22I2N2NaO5S+: 702.9236 [M+Na+]; found: 702.9225.
Compound 2j: White solid (136.1 mg, 70%); m.p. 160–1628C;
1
[a]2D0 =À60.08 (c=0.4 in CHCl3); H NMR (400 MHz, CDCl3): d=7.67
(d, J=8.2 Hz, 2H), 7.55 (dd, J=7.8, 1.6 Hz, 1H), 7.48 (dd, J=7.9,
1.0 Hz, 1H), 7.25 (d, J=9.2 Hz, 2H), 7.18 (t, J=7.5 Hz, 1H), 7.09 (td,
J=7.7, 1.7 Hz, 1H), 5.90 (s, 1H), 5.38 (dd, J=9.4, 6.2 Hz, 1H), 3.73
(s, 1H), 3.22 (dd, J=14.2, 6.2 Hz, 1H), 2.93 (dd, J=14.2, 9.6 Hz, 1H),
2.39 ppm (s, 3H); 13C NMR (125 MHz, CDCl3): d=144.2, 137.4, 134.6,
132.4, 129.6, 129.4, 129.2, 128.2, 127.9, 122.3, 93.2, 63.9, 57.8, 21.6,
À5.5 ppm; IR (neat): n˜ =3455 (br), 2956, 2923, 2853, 1714, 1596,
1470, 1440, 1348, 1160, 1112, 1036, 812, 758, 671, 588, 540 cmÀ1
;
MS (ESI): m/z: 670 [M+Na+]; HRMS: m/z calcd for
C17H16BrI2NNaO3S+: 669.8021 [M+Na+]; found: 669.8023.
Compound 2k: White solid (127.7 mg, 73%); m.p. 157–1598C;
1
[a]2D0 =À40.08 (c=1.0 in CHCl3); H NMR (400 MHz, [D6]DMSO): d=
7.72 (d, J=6.1 Hz, 1H), 7.26 (d, J=8.3 Hz, 2H), 7.11 (d, J=8.1 Hz,
2H), 7.03 (d, J=8.1 Hz, 2H), 6.88 (d, J=7.9 Hz, 2H), 5.75 (d, J=
5.6 Hz, 1H), 4.72 (dd, J=9.6, 6.2 Hz, 1H), 3.05 (dd, J=14.1, 6.2 Hz,
1H), 2.75 (dd, J=14.1, 9.6 Hz, 1H), 2.30 (s, 3H), 2.21 ppm (s, 3H);
13C NMR (100 MHz, [D6]DMSO): d=143.0, 137.6, 137.2, 134.9, 129.3,
128.9, 128.3, 127.3, 93.2, 64.1, 58.2, 21.4, 21.1, 2.5 ppm; IR (neat):
n˜ =3428 (br), 2959, 2917, 2850, 1614, 1515, 1442, 1330, 1257, 1154,
1128, 1106, 1042, 828, 674, 588, 546 cmÀ1; MS (ESI): m/z: 606 [M+
Na+]; HRMS: m/z calcd for C18H19I2NNaO3S+: 605.9073 [M+Na+];
found: 605.9066.
Compound 2 f: Oil (109.3 mg, 64%); [a]2D0 =À31.08 (c=1.0 in
1
CHCl3); H NMR (500 MHz, [D6]DMSO): d=7.73 (s, 1H), 7.27 (d, J=
8.3 Hz, 2H), 7.20–7.07 (m, 7H), 5.77 (s, 1H), 4.79 (dd, J=9.6, 6.3 Hz,
1H), 3.09 (dd, J=14.0, 6.3 Hz, 1H), 2.77 (dd, J=14.1, 9.6 Hz, 1H),
2.29 ppm (s, 3H); 13C NMR (125 MHz, [D6]DMSO): d=143.1, 138.1,
137.6, 129.3, 128.4, 128.3, 127.8, 127.2, 93.2, 64.3, 58.3, 21.4,
2.3 ppm; IR (neat): n˜ =3460 (br), 2950, 2927, 2852, 1710, 1605,
1487, 1308, 1216, 1159, 1058, 830, 646, 585, 553 cmÀ1; MS (ESI): m/
z: 592 [M+Na+]; HRMS: m/z calcd for C17H17I2NNaO3S+: 591.8916
[M+Na+]; found: 591.8918.
Compound 2l: White solid (129.4 mg, 72%); m.p. 166–1688C;
1
[a]2D0 =À35.08 (c=1.0 in CHCl3); H NMR (400 MHz, CDCl3): d=7.41
(d, J=8.3 Hz, 2H), 7.15 (d, J=8.7 Hz, 2H), 7.07 (d, J=8.1 Hz, 2H),
6.66 (d, J=8.7 Hz, 2H), 6.03 (d, J=1.6 Hz, 1H), 4.90 (dd, J=8.5,
7.3 Hz, 1H), 3.83–3.78 (m, 1H), 3.76 (s, 3H), 3.06 (dd, J=7.9, 1.6 Hz,
2H), 2.34 ppm (s, 3H); 13C NMR (125 MHz, CDCl3): d=159.4, 143.1,
136.7, 129.3, 129.0, 128.9, 127.5, 113.7, 92.7, 64.3, 58.7, 55.3, 21.4,
À2.5 ppm; IR (neat): n˜ =3419 (br), 2962, 2920, 2847, 1611, 15110,
1442, 1328, 1252, 1154, 1106, 1033, 826, 671, 579, 550 cmÀ1; MS
(ESI): m/z: 622 [M+Na+]; HRMS: m/z calcd for C18H19I2NNaO4S+:
621.9022 [M+Na+]; found: 621.9045.
Compound 2g: White solid (112.7 mg, 69%); m.p. 156–1588C;
1
[a]2D0 =À26.58 (c=2.0 in CHCl3); H NMR (500 MHz, [D6]DMSO): d=
7.77 (d, J=6.2 Hz, 1H), 7.29 (d, J=8.3 Hz, 2H), 7.20 (dd, J=8.7,
5.5 Hz, 2H), 7.14 (d, J=8.0 Hz, 2H), 6.90 (t, J=8.9 Hz, 2H), 5.76 (d,
J=6.1 Hz, 1H), 4.80 (dd, J=9.5, 6.3 Hz, 1H), 3.10 (dd, J=14.1,
6.3 Hz, 1H), 2.75 (dd, J=14.5, 9.9 Hz, 1H), 2.30 ppm (s, 3H);
13C NMR (125 MHz, [D6]DMSO): d=161.9 (d, J=243.7 Hz), 143.2,
137.6, 134.3, 130.3 (d, J=8.3 Hz), 129.3, 127.2, 115.1 (d, J=21.4 Hz),
93.2, 63.5, 58.2, 21.4, 1.9 ppm; IR (neat): n˜ =3458 (br), 2959, 2928,
2852, 1708, 1605, 1509, 1338, 1226, 1159, 1038, 836, 676, 587,
Compound 2m: Oil (92.7 mg, 60%); [a]2D0 =À51.08 (c=1.0 in
CHCl3); 1H NMR (500 MHz, CDCl3): d=5.74 (s, 1H), 4.09–4.00 (m,
1H), 3.84–3.67 (m, 1H), 3.09 (s, 3H), 2.98 (dd, J=14.0, 6.0 Hz, 1H),
2.87 (dd, J=14.0, 9.3 Hz, 1H), 2.18–2.08 (m, 1H), 1.70–1.59 (m, 1H),
1.37–1.18 (m, 10H), 0.88 ppm (t, J=6.8 Hz, 3H); 13C NMR (100 MHz,
CDCl3): d=92.8, 61.3, 54.7, 42.3, 34.1, 31.7, 29.4, 29.1, 25.4, 22.5,
14.0, À2.2 ppm; IR (neat): n˜ =3461 (br), 2956, 2925, 2852, 1658,
1459, 1338, 1156, 1035, 971, 769, 660, 553 cmÀ1; MS (ESI): m/z: 538
[M+Na+]; HRMS: m/z calcd for C18H19I2NNaO4S+: 537.9386 [M+
Na+]; found: 537.9372.
545 cmÀ1
;
MS (ESI): m/z: 610 [M+Na+]; HRMS calcd for
C17H16FI2NNaO3S+: 609.8822 [M+Na+]; found: 609.8851.
Compound 2h: Oil (117.7 mg, 65%); [a]2D0 =À64.58 (c=0.5 in
1
CHCl3); H NMR (400 MHz, CDCl3): d=7.42 (d, J=8.2 Hz, 2H), 7.17
(d, J=8.4 Hz, 2H), 7.12–7.06 (m, 4H), 6.04 (s, 1H), 4.89 (dd, J=8.9,
6.8 Hz, 1H), 3.85 (s, 1H), 3.20–2.92 (m, 2H), 2.37 ppm (s, 3H);
13C NMR (100 MHz, CDCl3): d=143.7, 136.3, 135.7, 133.9, 129.3,
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(d, J=8.3 Hz, 2H), 7.29–7.19 (m, 6H), 5.74 (d, J=12.2 Hz, 1H), 4.89
(dd, J=50.6, 3.0 Hz, 1H), 4.62 (dd, J=9.8, 6.7 Hz, 1H), 3.91 (s, 1H),
2.55–2.32 (m, 1H), 2.41 (s, 3H), 2.32–2.11 ppm (m, 1H); 13C NMR
(100 MHz, CDCl3): d=144.0, 139.4, 135.2, 133.5, 129.5, 128.6, 128.4,
127.5, 93.9 (d, J=178.0 Hz), 87.9 (d, J=33.2 Hz), 62.4, 40.9 (d, J=
20.3 Hz), 21.5 ppm; IR (neat): n˜ =3480 (br), 2919, 2849, 1492, 1339,
1160, 1090, 1038, 1013, 817, 675, 598 cmÀ1; MS (ESI): m/z: 392 [M+
Na+]; HRMS: m/z calcd for C17H17ClFNNaO3S+: 392.0494 [M+Na+];
found: 392.0502.
General procedure for the preparation of 3-fluoropyrrolidin-
2-ols 3
Selectfluor (223.2 mg, 0.63 mmol), Et3N (2.0 mL, 0.003 mmolmLÀ1 in
DCE) and [BrettPhosAuNTf2] (15.3 mg, 0.015 mmol) were added, in
this order, to a solution of homopropargyl amide 1 (0.30 mmol) in
DCE (4.0 mL) at RT. The reaction mixture was stirred at 608C, and
the progress of the reaction was monitored by TLC; the reaction
typically took 15 h. On completion, the reaction mixture was con-
centrated and the residue was purified by column chromatography
on silica gel (hexanes/ethyl acetate) to afford the desired product
3.
Compound 3 f: Oil (74.5 mg, 60%); [a]2D0 =À185.08 (c=1.0 in
1
CHCl3); H NMR (400 MHz, CDCl3): d=7.59 (d, J=8.2 Hz, 2H), 7.37
(d, J=8.3 Hz, 2H), 7.27–7.17 (m, 4H), 5.74 (d, J=12.2 Hz, 1H), 4.89
(dd, J=50.5, 2.6 Hz, 1H), 4.61 (dd, J=9.8, 6.8 Hz, 1H), 4.04–3.92 (m,
2H), 2.56–2.41 (m, 1H), 2.42 (s, 3H), 2.31–2.10 ppm (m, 1H);
13C NMR (100 MHz, CDCl3): d=144.0, 139.8, 135.2 131.6, 129.5,
128.7, 127.5 121.6, 93.8 (d, J=178.1 Hz), 87.8 (d, J=33.3 Hz), 62.5,
40.9 (d, J=20.4 Hz), 21.5 ppm; IR (neat): n˜ =3472 (br), 2924, 2851,
1597, 1488, 1341, 1160, 1094, 1039, 1010, 816, 670, 598 cmÀ1; MS
(ESI): m/z: 435 [M+Na+]; HRMS: m/z calcd for C17H17BrFNNaO3S+:
435.9989 [M+Na+]; found: 435.9998.
Compound 3a: Oil (65.5 mg, 61%); [a]2D0 =À120.08 (c=1.0 in
1
CHCl3); H NMR (400 MHz, CDCl3): d=7.72 (d, J=8.3 Hz, 2H), 7.30
(d, J=8.0 Hz, 2H), 5.48 (dd, J=12.3, 2.0 Hz, 1H), 4.80 (dd, J=50.7,
3.2 Hz, 1H), 3.59 (dtt, J=12.3, 6.0, 3.0 Hz, 1H), 3.27 (s, 1H), 2.42 (s,
3H), 2.26–1.93 (m, 3H), 1.69–1.57 (m, 1H), 1.37–1.20 (m, 10H),
0.89 ppm (t, J=6.8 Hz, 3H); 13C NMR (100 MHz, CDCl3): d=143.8,
135.3, 129.6, 127.4, 93.9 (d, J=176.4 Hz), 88.3 (d, J=33.6 Hz), 59.7,
36.4, 35.9 (d, J=20.5 Hz), 31.8, 29.4, 29.2, 25.3, 22.6, 21.5,
14.0 ppm; IR (neat): n˜ =3460 (br), 2924, 2853, 1598, 1464, 1341,
1162, 1093, 1026, 814, 739, 665, 598 cmÀ1; MS (ESI): m/z: 380 [M+
Na+]; HRMS: m/z calcd for C18H28FNNaO3S+: 380.1666 [M+Na+]:
found: 380.1669.
Compound 3g: White solid (74.4 mg, 71%); m.p. 138–1408C;
1
[a]2D0 =À110.08 (c=1.0 in CHCl3); H NMR (400 MHz, CDCl3): d=7.60
(d, J=8.2 Hz, 2H), 7.23 (d, J=8.0 Hz, 4H), 7.08 (d, J=7.8 Hz, 2H),
5.70 (d, J=12.6 Hz, 1H), 4.89 (dd, J=50.6, 2.8 Hz, 1H), 4.60 (dd, J=
9.8, 6.7 Hz, 1H), 3.74 (s, 1H), 2.40 (s, 3H), 2.53–2.15 (m, 2H),
2.32 ppm (s, 3H); 13C NMR (100 MHz, CDCl3): d=143.7, 137.7, 137.4,
135.2, 129.4, 129.2 127.5, 126.8, 94.0 (d, J=177.6 Hz), 87.9 (d, J=
33.5 Hz), 62.9, 40.9 (d, J=20.2 Hz), 21.5, 21.1 ppm; IR (neat): n˜ =
3469 (br), 2923, 2853, 1597, 1515, 1340, 1159, 1094, 1039, 813, 664,
598 cmÀ1; MS (ESI): m/z: 372 [M+Na+]; HRMS: m/z calcd for
C18H20FNNaO3S+: 372.1040 [M+Na+]; found: 372.1044.
Compound 3b: White solid (55.3 mg, 54%); m.p. 126–1288C;
1
[a]2D0 =À73.58 (c=1.0 in CHCl3); H NMR (400 MHz, CDCl3): d=7.72
(d, J=8.2 Hz, 2H), 7.30 (d, J=8.1 Hz, 2H), 5.47 (d, J=12.7 Hz, 1H),
4.76 (dd, J=50.9, 3.1 Hz, 1H), 3.66–3.56 (m, 1H), 3.05–2.97 (m, 1H),
2.42 (s, 3H), 2.21–2.01 (m, 2H), 1.98–1.83 (m, 2H), 1.83–1.66 (m,
3H), 1.58 (d, J=12.4 Hz, 1H), 1.37–1.19 (m, 2H), 1.17–1.04 (m, 1H),
1.00–0.80 ppm (m, 2H); 13C NMR (100 MHz, CDCl3): d=143.8, 135.2,
129.6, 127.4, 93.9 (d, J=176.4 Hz), 88.2 (d, J=33.6 Hz), 64.1, 39.8,
30.7 (d, J=20.6 Hz), 30.4, 26.6, 26.5, 25.8, 25.2, 21.5 ppm; IR (neat):
n˜ =3468 (br), 2925, 2852, 1598, 1449, 1341, 1161, 1093, 1029, 814,
667, 598, 548 cmÀ1; MS (ESI): m/z: 364 [M+Na+]; HRMS: m/z calcd
for C17H24FNNaO3S+: 364.1353 [M+Na+]; found: 364.1357.
Compound 3h: White solid (68.0 mg, 62%); m.p. 144–1468C;
1
[a]2D0 =À135.08 (c=1.0 in CHCl3); H NMR (400 MHz, CDCl3): d=7.60
(d, J=8.3 Hz, 2H), 7.28–7.22 (m, 4H), 6.80 (d, J=8.7 Hz, 2H), 5.72
(d, J=12.5 Hz, 1H), 4.90 (dd, J=50.6, 2.9 Hz, 1H), 4.60 (dd, J=9.9,
6.6 Hz, 1H), 3.88–3.79 (m, 1H), 3.78 (s, 3H), 2.52–2.41 (m, 1H), 2.40
(s, 3H), 2.36–2.16 ppm (m, 1H); 13C NMR (100 MHz, CDCl3): d=
159.1, 143.6, 135.3, 132.6, 129.4, 128.2, 127.5, 113.8, 93.9 (d, J=
177.5 Hz), 87.8 (d, J=33.5 Hz), 62.7, 55.2, 40.9 (d, J=20.3 Hz),
21.5 ppm; IR (neat): n˜ =3478 (br), 2926, 2852, 1613, 1598, 1514,
1463, 1340, 1247, 1160, 1094, 1034, 829, 674, 597 cmÀ1; MS (ESI):
m/z: 388 [M+Na+]; HRMS: m/z calcd for C18H20FNNaO4S+:
388.0989 [M+Na+]; found: 388.0922.
Compound 3c: Oil (81.7 mg, 61%); [a]2D0 =À93.58 (c=1.0 in CHCl3);
1H NMR (400 MHz, CDCl3): d=7.71 (d, J=8.3 Hz, 2H), 7.46–7.29 (m,
5H), 7.28 (d, J=7.9 Hz, 2H), 5.47 (d, J=12.1 Hz, 1H), 4.77 (dd, J=
50.7, 3.1 Hz, 1H), 4.50 (s, 2H), 3.63–3.51 (m, 2H), 3.47 (t, J=6.5 Hz,
2H), 2.40 (s, 3H), 2.22–1.87 (m, 3H), 1.70–1.56 (m, 3H), 1.45–
1.23 ppm (m, 4H); 13C NMR (100 MHz, CDCl3): d=143.7, 138.5,
135.1, 129.5, 128.3, 127.6 127.4, 127.3, 93.8 (d, J=176.9 Hz), 88.1 (d,
J=33.1 Hz), 72.7, 70.1, 59.4, 36.2, 35.7 (d, J=20.5 Hz), 29.5, 26.0,
25.0, 21.5 ppm; IR (neat): n˜ =3471 (br), 2934, 2859, 1598, 1495,
1453, 1344, 1162, 1094, 1027, 815, 738, 699, 665, 597, 550 cmÀ1; MS
(ESI): m/z: 458 [M+Na+]; HRMS: m/z calcd for C23H30FNNaO4S+:
458.1772 [M+Na+]; found: 458.1772.
Procedure for the preparation of 4a
Anhydrous DMF (4 mL) was added to a flame-dried flask, and the
flask was purged with N2. Sodium hydride (14.4 mg, 0.36 mmol,
1.2 equiv, 60% in mineral oil) was added followed by trimethyl-
phosphoroacetate (65.5 mg, 0.36 mmol, 1.2 equiv). The mixture
was stirred for 1 h at RT then hemiaminal 2a (177.3 mg, 0.3 mmol)
in a solution of DMF (2 mL) was added. The reaction mixture was
stirred for 12 h at RT then quenched with a saturated aqueous so-
lution of NH4Cl (30 mL). The resulting solution was extracted with
EtOAc (2”30 mL) and washed with brine (2”30 mL). The com-
bined organic layers were dried over anhydrous MgSO4 and con-
centrated under reduced pressure. Compound 4a was obtained as
a clear oil (86.2 mg, 73%) after column chromatography on silica
gel.[20] [a]D20 =+72.08 (c=0.5 in CHCl3); 99% ee (HPLC: Chiralcel IC
column; 10:90 iPrOH/hexane; flow rate=0.8 mLminÀ1; l=200 nm;
tR =66.21 (major), 63.85 min (minor)); 1H NMR (400 MHz, CDCl3):
d=7.69 (d, J=8.5 Hz, 2H), 7.36 (d, J=8.5 Hz, 2H), 6.91 (dd, J=
15.6, 5.4 Hz, 1H), 6.09 (dd, J=15.6, 1.3 Hz, 1H), 4.30 (dd, J=13.2,
Compound 3d: White solid (55.3 mg, 55%); m.p. 145–1478C;
[a]2D0 =À120.08 (c=0.5 in CHCl3); 99% ee (HPLC: Chiralcel IB
column; 10:90 iPrOH/hexane; flow rate=0.6 mLminÀ1; l=200 nm;
1
tR =11.27 (major), 12.53 min (minor)); H NMR (400 MHz, CDCl3): d=
7.61 (d, J=8.1 Hz, 2H), 7.34 (d, J=6.8 Hz, 2H), 7.31–7.19 (m, 5H),
5.73 (d, J=12.4 Hz, 1H), 4.90 (dd, J=50.6, 2.7 Hz, 1H), 4.65 (dd, J=
9.8, 6.8 Hz, 1H), 3.73 (s, 1H), 2.56–2.16 ppm (m, 5H); 13C NMR
(100 MHz, CDCl3): d=143.7, 140.7, 135.3, 129.5, 128.5, 127.7, 127.5,
126.9, 94.0 (d, J=177.6 Hz), 88.0 (d, J=33.5 Hz), 63.2, 41.0 (d, J=
20.3 Hz), 21.5 ppm; IR (neat): n˜ =3473 (br), 2983, 2926, 1598, 1494,
1456, 1339, 1160, 1094, 814, 736, 597 cmÀ1; MS (ESI): m/z: 358 [M+
Na+]; HRMS: m/z calcd for C17H18FNNaO3S+: 358.0884 [M+Na+];
found: 358.0885.
Compound 3e: White solid (62.1 mg, 56%); m.p. 157–1598C;
1
[a]2D0 =À128.08 (c=1.0 in CHCl3); H NMR (400 MHz, CDCl3): d=7.60
Chem. Eur. J. 2016, 22, 2282 – 2290
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ˇ
Liang, J. Org. Chem. 2013, 78, 12018; k) L. Bedrac, J. Iskra, Adv. Synth.
7.7 Hz, 1H), 3.86–3.77 (m, 1H), 3.74 (s, 3H), 2.46 (s, 3H), 2.48–2.39
(m, 1H), 2.34–2.24 (m, 1H), 1.87–1.77 (m, 1H), 1.74–1.65 (m, 1H),
1.31–1.16 (m, 10H), 0.88 ppm (t, J=6.9 Hz, 3H); 13C NMR (125 MHz,
CDCl3): d=166.6, 146.3, 144.3, 132.7, 129.7, 128.4, 121.9, 60.7, 58.8,
51.6, 36.2, 31.7, 29.4, 29.3, 29.1, 24.1, 22.6, 21.6, 14.1 ppm; IR (neat):
n˜ =2926, 2855, 1726 (s), 1662, 1597, 1541, 1436, 1347, 1162, 1038,
987, 816, 665, 605 cmÀ1; MS (ESI): m/z: 416 [M+Na+]; HRMS: m/z
calcd for C21H31NNaO4S+: 416.1866 [M+Na+]; found: 416.1869.
Catal. 2013, 355, 1243; l) A. Kumar, P. Lohan, O. Prakash, Synth.
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S. Schetter, A. Littmann, M. Rudolph, M. Hamzic, J. Visus, F. Rominger,
W. Frey, J. W. Bats, Chem. Eur. J. 2010, 16, 956.
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Procedure for the preparation of 5a
Compound 5a was prepared according to the procedure described
above for 4a. Clear oil; 100.5 mg, 81%; [a]2D0 = +50.08 (c=0.2 in
CHCl3); 99% ee (HPLC: Chiralcel IC column; 10:90 iPrOH/hexane;
flow rate=0.6 mLminÀ1; l=200 nm; tR =32.80 (major), 26.29 min
1
(minor)); H NMR (400 MHz, CDCl3): d=7.73 (d, J=8.3 Hz, 2H), 7.31
(d, J=8.0 Hz, 2H), 4.83 (dd, J=50.8, 3.0 Hz, 1H), 4.29–4.18 (m, 1H),
3.72 (s, 3H), 3.59–3.50 (m, 1H), 2.95 (ddd, J=16.3, 4.4, 2.7 Hz, 1H),
2.42 (s, 3H), 2.37 (ddd, J=16.3, 10.8, 1.2 Hz, 1H), 2.23–2.11 (m, 2H),
1.87–1.50 (m, 2H), 1.35–1.21 (m, 10H), 0.89 ppm (t, J=6.9 Hz, 3H);
13C NMR (100 MHz, CDCl3): d=170.5, 143.7, 133.7, 129.5, 127.8, 94.1
(d, J=179.4 Hz), 64.2 (d, J=23.9 Hz), 59.6, 51.9, 39.4 (d, J=10.1 Hz),
36.6, 36.5 (d, J=21.2 Hz), 31.8, 29.4, 29.2, 25.4, 22.6, 21.5,
14.1 ppm; IR (neat): n˜ =2955, 2925, 2854, 1739 (s), 1599, 1494,
1463, 1348, 1311, 1162, 1093, 1026, 978, 815, 740, 663 cmÀ1; MS
(ESI): m/z: 436 [M+Na+]; HRMS: m/z calcd for C21H32FNNaO4S+:
436.1928 [M+Na+]; found: 436.1928.
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Acknowledgements
We are grateful for financial support from the National Natural
Science Foundation of China (No. 21102119 and 21272191), the
Natural Science Foundation of Fujian Province for Distinguish-
ed Young Scholars (No. 2015J06003), National Found for Fos-
tering Talents of Basic Science (NFFTBS, No. J1310024), the Pro-
gram for Changjiang Scholars and Innovative Research Team in
University (PCSIRT), and the XMU Training Program of Innova-
tion and Enterpreneurship for Undergraduates.
Keywords: cycloisomerization
·
gold
·
halogenation
·
heterocycles · homogeneous catalysis
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Full Paper
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reaction conditions. We found that the reaction of D with Selectfluor ef-
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Received: September 28, 2015
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Published online on January 8, 2016
Chem. Eur. J. 2016, 22, 2282 – 2290
www.chemeurj.org
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ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim