Chemical

Science
View Article Online
EDGE ARTICLE View Journal | View Issue

Rhodium-catalyzed regioselective opening of vinyl

epoxides with Et3N$3HF reagent – formation of
allylic fluorohydrins†
Cite this: Chem. Sci., 2014, 5, 291

Qi Zhang and Hien M. Nguyen*

A highly regioselective rhodium-catalyzed ring-opening of vinyl epoxides with Et3N$3HF reagent to form
Published on 03 October 2013. Downloaded on 14/05/2016 00:48:16.

Received 11th July 2013

Accepted 30th September 2013
DOI: 10.1039/c3sc51949j
www.rsc.org/chemicalscience
branched allylic fluorohydrins is described. The reaction occurs at room temperature under ambient air
and relies on RhCOD2BF4 as an effective catalyst, providing the desired 1,2-addition allylic fluorohydrins
in moderate to good yields with excellent levels of regioselectivity. Mechanistic studies demonstrate that
the regioselective ring-opening of enantiopure vinyl epoxide occurs with inversion of stereochemistry.

excellent selectivity (Scheme 1a).6 In an effort to expand the

Introduction
The many important roles that uorine-containing compounds
play in pharmaceuticals, agrochemicals, medical imaging, and
high-performance materials have made the synthesis of this
class of molecules a major focus in recent years.1 Consequently,
practical and elegant methods have been developed for the
construction of aryl–F and alkyl–F bonds.2,3 In contrast, the
synthesis of allylic uorides remains relatively underdevel-
oped.4 In recent years, a few examples of the transition-metal-
catalyzed uorination of allylic electrophiles with uoride ions
have been reported for the regio- and enantioselective prepa-
ration of allylic uoride products.5 We recently reported that
[IrClCOD]2 is an effective catalyst for the regioselective uori-
nation of allylic trichloroacetimidates with Et3N$3HF, providing
secondary and tertiary allylic uorides with good yields and
capabilities of our uorination method, we sought the devel-
opment of a variant proceeding via the opening of vinyl epox-
ides, as depicted in Scheme 1b.
Vinyl epoxides are commonly used building blocks for the
synthesis of biologically active targets.7 They are quite reactive
in the presence of transition-metal catalysts.8 Palladium is most
frequently used to promote the ring-opening of vinyl epoxides
with a wide variety of nucleophiles, leading to 1,4-addition
products due to the electron-decient nature of the vinyl
epoxide oxygen.9 The 1,2-addition products can be achieved by
choice of the ligand and co-catalysts.10 Rhodium has also been
reported as an effective catalyst for the ring-opening of vinyl
epoxides with both anilines and alcohols to provide trans-1,2-
amino alcohols or alkoxy alcohols, respectively, in good yield
and with high levels of diastereo- and regio-selectivity.11 Even
though the transition-metal-catalyzed asymmetric ring-opening
of terminal epoxides1e,12 and oxabicyclic olens13 using the
nucleophilic uoride ion has been developed, to the best of our
knowledge there are no reports on the transition-metal-cata-
lyzed regioselective ring-opening of vinyl epoxides with nucle-
ophilic uoride reagents.14

Results and discussion

Scheme 1 Transition-metal-catalyzed fluorination.
University of Iowa, Department of Chemistry, Iowa City, IA 52242, USA. E-mail:
hien-nguyen@uiowa.edu
† Electronic supplementary information (ESI) available: Experimental procedures,
characterization data for all new compounds. CCDC 964273. For ESI and
crystallographic data in CIF or other electronic format see DOI:
10.1039/c3sc51949j
Initial studies focused on establishing the regioselectivity of the
opening of vinyl epoxide 1 with Et3N$3HF reagent (Table 1).
Using our optimized conditions for the iridium-catalyzed uo-
rination of allylic trichloroacetimidates,6 we began our investi-
gation with 2.5 mol% [IrCl(COD)]2 (entry 1) in Et2O at room
temperature. The 1,2-addition allylic uorohydrin 2A was
obtained in 37% NMR yield. A number of rhodium(I) catalysts
were then investigated. RhCOD2BF4 (entry 4) produced the best
result to provide an 88% NMR yield of 2A.15 We subsequently
screened a number of solvents, and THF (entry 7) provided 2A
with the highest NMR yield (92%). In all cases with rhodium

This journal is © The Royal Society of Chemistry 2014 Chem. Sci., 2014, 5, 291–296 | 291
 View Article Online

Chemical Science Edge Article

Table 1 Studies with ring-opening of vinyl epoxidea

Entry Catalyst Loading (mol%) F source Solvent Time (h) NMR yield 2Ab (%) Isolated yield 2c (%)

1 [IrCl(COD)]2 2.5 Et3N$3HF Et2O 2 37

2 [RhCl(COD)]2 2.5 Et3N$3HF Et2O 2 55
3 RhCOD2OTf 5 Et3N$3HF Et2O 0.5 70
4 RhCOD2BF4 5 Et3N$3HF Et2O 0.5 88
5 RhCOD2BF4 5 Et3N$3HF MTBE 0.5 71
6 RhCOD2BF4 5 Et3N$3HF CH2Cl2 0.5 79
7 RhCOD2BF4 5 Et3N$3HF THF 0.5 92
Published on 03 October 2013. Downloaded on 14/05/2016 00:48:16.

8 None 0 Et3N$3HF Et2O 18 23

9 None 0 Et3N$3HF THF 18 35
10 RhCOD2BF4 5 Pyridine$HF THF 14 12
11 RhCOD2BF4 5 CsF THF 18 0
12 RhCOD2BF4 5 TBAT THF 18 0
13 RhCOD2BF4 5 AgF THF 18 0
14 RhCOD2BF4 5 KF THF 18 0
15 RhCOD2BF4 5 Et3N$3HF Et2O 0.5 89 (88)d 79 (76)d
a
All reactions were conducted with 0.2 mmol of vinyl epoxide 1. b The NMR yield of allylic uorohydrin 2A was determined by 19F NMR analysis of
the crude reaction mixture using PhCF3 as an internal standard. c For full analyses, crude product 2A was then transformed into the isolable allylic
4-uorobenzoate 2 and the isolated yield was determined. d The reaction was performed with 10 mmol of vinyl epoxide 1.

catalysts, the ring-opening of 1 proceeded to completion within
30 min, and the undesired 1,4-addition product was not
observed. A control experiment (entries 8 and 9) was performed
without the catalyst, and a 23–35% NMR yield of allylic uo-
rohydrin 2A was observed aer 18 h.16 Olah’s reagent performed
poorly under rhodium conditions (entry 10) with only 12%
conversion aer the reaction had been stirring for 14 h. Other
nucleophilic uoride sources (CsF, TBAT, AgF, and KF) showed
no reactivity (entries 11–14). For full analysis and isolated yield
determination, crude uorohydrin 2A was treated with 4-uo-
robenzoyl chloride (entry 15), and the corresponding allylic
uoride 2 was isolated in 79% yield over two steps.17 To
demonstrate the reproducibility and scalability of this reaction,
10 mmol of epoxide 1 (entry 15) was subjected to similar
conditions: uoride product 2 was obtained in 76% yield, which
is comparable to the use of 0.2 mmol of substrate 1.
With the optimized conditions in hand, we proceeded to
explore the scope and limitation of the rhodium-catalyzed
regioselective ring-opening of vinyl epoxides (Table 2). We
discovered that ve- and seven-membered ring vinyl epoxides
performed poorly under the same reaction protocol. We
reasoned that acyclic vinyl epoxides possessing greater confor-
mational exibility may undergo ring-opening in the presence
of RhCOD2BF4 and Et3N$3HF reagent. To our excitement,
various acylic vinyl epoxide substrates 3–13 (Table 2) proceeded
smoothly under rhodium conditions. Because most epoxide
substrates are too volatile for isolation, all allylic uorohydrins
14A–24A were converted into the 4-uoro-benzoate derivatives
14–24 for full analyses and isolated yield calculation. Overall,
the reactivity of the vinyl epoxides is dependent on both the
steric and electronic nature of the substituents at the C(1)- and
C(2)-position of the allyl moiety. For instance, the presence of
the methyl group at the C(2)-position of vinyl epoxides 3 and 4
(Table 2, entries 1 and 2) provided allylic uorides 14 and 15 in
60% and 62% yield, respectively, compared to their epoxide
counterparts 5–8 (43–58%, entries 3–6). We discovered that
vinyl epoxides containing the C(1)-electron-donating groups
(e.g. 4-methoxy-phenyl) only resulted in decomposition. In
contrast, electron-withdrawing substituents at the C(1)-position
of vinyl epoxides 4–7 (entries 2–5) provided allylic uorohydrins
15A–18A in 50–76% NMR yield (43–62% of their isolable uo-
ride derivatives). On the other hand, increasing the steric
hindrance at the C(2)-position (entry 7) requires a signicantly
longer reaction time (10 h vs. 1 h) and allylic uoride 20 was
isolated in 59% yield. Vinyl epoxide 10 (entry 8) bearing the
primary alkyl functionality also performed adequately to
provide the allylic uorohydrin 21A in 61% NMR yield.
The success of butadiene monoepoxide 11 (Table 2, entry 9)
to form uorohydrin 22A (50% NMR yield) and its isolable
uoride 22 (44–49%) led to our studies of isoprene monoep-
oxide 12 (entry 10) and C(2)-substituted methyl substrate 13
(entry 11). The reactions were fast (0.5 h) and proceeded with
complete regioselectivity, providing tertiary allylic uorohy-
drins 23A and 24A, respectively, in good NMR yields (65–80%).
As expected, the more hindered vinyl epoxide 13 provided allylic
uorohydrin 24A in lower yield than that of substrate 12. These
results are consistent with what has been observed when
comparing the ring-opening of vinyl epoxide 3 (entry 1) to that
of the more hindered 9 (entry 7), where the NMR yield is 82% vs.
73%.

292 | Chem. Sci., 2014, 5, 291–296 This journal is © The Royal Society of Chemistry 2014
 View Article Online

Edge Article Chemical Science

Table 2 Survey of secondary and tertiary vinyl epoxidesa

Allylic uorides
Entry Vinyl epoxides Time (h) Allylic uorohydrins NMR yielda isolated yield

1 3: R ¼ H 1 14A (82%)d 14 (60%)b

2 4: R ¼ Cl 1 15A (76%)d 15 (62%)c
Published on 03 October 2013. Downloaded on 14/05/2016 00:48:16.

3 5: R ¼ 4-Cl 1 16A (64%) 16 (46%)b

4 6: R ¼ 3-Br 1 17A (63%) 17 (43%)c
5 7: R ¼ 4-CF3 4 18A (50%) 18 (46%)b
6 8: R ¼H 1 19A (69%) 19 (58%)b

7 10 20A (73%)e 20 (59%)b

8 3 21A (61%) f 21 (48%)b

9 1 22A (50%) 22 (49%)b

22A (50%) 22 (44%)c

10 12: R ¼ H 0.5 23A (80%) 23 (70%)b

11 13: R ¼ Me 0.5 24A (65%) 24 (56%)b
a
NMR yields of allylic uorohydrins 14A–24A were determined by 19F NMR analysis of the reaction mixture using PhCF3 as an internal standard.
b
Reactions were performed using 0.2 mmol of vinyl epoxides. c Reactions were performed using 0.5 mmol of vinyl epoxides. d An 11 : 1 mixture of
1,2-addition products 14A and 15A and their undesired 1,4-addition products was observed. e A 6 : 1 mixture of 1,2-addition product 20A and its
undesired 1,4-addition product was observed. f A 1.7 : 1 mixture of 1,2-addition product 21A and undesired 1,4-addition product was observed.

With the ability to access a number of allylic uorohydrins in
moderate to good yields and with excellent regioselectivity, we
next sought to establish the utility of this method by trans-
forming tertiary allylic uorohydrins into the tertiary alkyl
uorides 25 and 26 (Scheme 2), which could be potentially used
as structural motifs of anticancer ether phospholipid
compounds.18 One-pot regioselective ring-opening of vinyl
epoxides 12 and 13 followed by hydrogenation and benzoylation
furnished tertiary uorides 25 and 26 in 52% and 50% yield,
respectively.
To determine if Lewis acid behavior alone was responsible
for reactivity with RhCOD2BF4, we conducted control experi-
ments with cyclohexyl epoxide 27 and styrene oxide 28 (Scheme
3) under the same rhodium conditions. No products were
observed aer 18 h, suggesting that RhCOD2BF4 is likely not
acting as a Lewis acid and the presence of an alkene unit is
required for the reaction to occur. These results are consistent
with previously reported results for the rhodium-catalyzed
regioselective ring-opening of vinyl epoxides with alcohols and
anilines.11

Scheme 2 Conversion of allylic fluorohydrins into tertiary alkyl

fluorides. Scheme 3 Control experiments.

This journal is © The Royal Society of Chemistry 2014 Chem. Sci., 2014, 5, 291–296 | 293

Chemical Science
Scheme 4 Stereospecific ring-opening of vinyl epoxides.
Published on 03 October 2013. Downloaded on 14/05/2016 00:48:16.
Scheme 5 Derivatization of fluoride 22 for X-ray analysis.
Scheme 6 Proposed mechanism for rhodium-catalyzed ring-opening
of vinyl epoxides lacking the C(1)-substituent.
To gain some mechanistic insight, enantiopure epoxide (S)-
11 was subjected to standard rhodium conditions (Scheme 4a).
Allylic uoride 22 was isolated in 43% yield with 69% ee. When
the ring opening of (S)-11 was conducted in the absence of the
catalyst, 22 was isolated in only 14% yield, albeit with a higher
enantioselectivity (80% ee).14b,19,20 On the other hand, opening
of enantiopure epoxide (R)-8 containing the C(1)-phenyl group,
with and without the rhodium catalyst (Scheme 4b), resulted in
signicant racemization of allylic uoride 19 (10–13% ee).
To establish the absolute stereochemistry of the allylic
uoride product, 22 was subjected to cross-metathesis with 4-
bromo-styrene 29 (Scheme 5). The major enantiomer of diene
product 30 (67% ee) was shown by X-ray crystallographic anal-
ysis to be R-congured.20 Collectively, the data illustrates that
the rhodium-catalyzed regioselective opening of vinyl epoxide
with Et3N$3HF proceeds with inversion of stereochemical
conguration.21 This is opposite to what has been reported for
palladium-catalyzed allylic uorination.5a,f
Based on the results obtained in Schemes 4 and 5, we
propose the following mechanistic rationale for the regiose-
lective ring-opening of vinyl epoxides lacking the C(1)-func-
tional group.22 The rhodium catalyst rst coordinates to the
olen of (S)-11 to form rhodium–alkene complex 31 (Scheme 6).
294 | Chem. Sci., 2014, 5, 291–296
View Article Online
Edge Article
Subsequent ionization of 31 provides the p-allylrhodium
intermediate 32.23 We hypothesize that hydrogen uoride may
rst attack the rhodium center of 32 to form the corresponding
uoride–rhodium complex 33. Fluoride is widely regarded as a
hard nucleophile,24 which has been known to bind to the metal
center of the allyl–metal complex in allylic substitution.25
Protonation of the alkoxide followed by reductive elimination
and benzoylation affords the corresponding (R)-allylic uoride
22 with retention of stereochemistry, which is conrmed by X-
ray crystallographic analysis.20 To rationalize the excellent levels
of regioselectivity for the 1,2-addition products, we hypothesize
that the uoride ion selectively attacks the more substituted
allyl position of 34. Because (R)-22 was generated in 69% ee
(Scheme 4a), we propose that nucleophilic attack by uoride
onto the p-allylrhodium complex 32 (Scheme 6) must occur
faster than isomerization of complex 32 to its corresponding
ent-32. Alternatively, the erosion of enantioselectivity observed
in product 22 could arise if the allylic uorohydrin intermediate
is undergoing a degenerate substitution reaction with the
Et3N$3HF reagent.26
Conclusions
We have developed a rhodium-catalyzed methodology that
efficiently facilitates the regioselective ring-opening of a variety
of vinyl epoxides with Et3N$3HF to provide the corresponding
1,2-addition allylic uorohydrins in moderate to good yields
and with excellent regioselectivity. Mechanistic studies show
that the opening of vinyl epoxides occurs with inversion of
conguration. The operationally simple, mild, and rapid
conditions make this method an attractive strategy for the
incorporation of uorine-18 ion into the allyl moiety of vinyl
epoxides. Application of the ring-opening of vinyl epoxide
procedure to the preparation of uorine-18 radiotracers will be
reported in due course.
Acknowledgements
We thank the University of Iowa for nancial support and Dr
Dale Swenson for X-ray crystallographic analysis. Q.Z. also
thanks the University of Iowa for the Graduate Research
Fellowship.
Notes and references
1 (a) K. Müller, C. Faeh and F. Diederich, Science, 2007, 317,
1881; (b) V. Gouverneur, Science, 2009, 325, 1630; (c)
X.-L. Qui, X.-H. Xu and F.-L. Qing, Tetrahedron, 2010, 66,
789; (d) T. Furuya, A. S. Kamlet and T. Ritter, Nature, 2011,
473, 470; (e) C. Hollingworth and V. Gouverneur, Chem.
Commun., 2012, 48, 2929.
2 Representative examples of non-radioactive aryl–uorine
bonds: (a) D. V. Yandulov and N. T. Tran, J. Am. Chem.
Soc., 2007, 129, 1342; (b) D. A. Watson, M. Su,
G. Teverovskiy, Y. Zhang, J. Garcı́a-Fortanet, T. Kinzel and
S. L. Buchwald, Science, 2009, 325, 1661; (c) N. D. Ball and
M. S. Sanford, J. Am. Chem. Soc., 2009, 131, 3796; (d)
This journal is © The Royal Society of Chemistry 2014

Edge Article
X. Wang, T.-S. Mei and J.-Q. Yu, J. Am. Chem. Soc., 2009, 131,
7520; (e) T. Furuya, A. E. Strom and T. Ritter, J. Am. Chem.
Soc., 2009, 131, 1662; (f) P. Tang, T. Furuya and T. Ritter, J.
Am. Chem. Soc., 2010, 132, 12150; (g) P. Tang, W. Wang
and T. Ritter, J. Am. Chem. Soc., 2011, 133, 11482; (h) T. Xu,
X. Mu, H. Peng and G. Liu, Angew. Chem., Int. Ed., 2011,
50, 8176; (i) P. S. Fier and Hartwig, J. Am. Chem. Soc., 2012,
134, 10795; (j) T. Truong, K. Klimovica and O. Daugulis, J.
Am. Chem. Soc., 2013, 135, 9342; (k) P. S. Fier, J. Luo and
J. F. Hartwig, J. Am. Chem. Soc., 2013, 135, 2552.
3 Representative examples of non-radioactive alkyl–uorine
bonds: (a) D. D. Steiner, N. Mase and C. F. Barbas, Angew.
Chem., Int. Ed., 2005, 44, 3706; (b) M. Marigo,
D. Fielenbach, A. Braunton, A. Kjærsgaard and
K. A. Jørgensen, Angew. Chem., Int. Ed., 2005, 44, 3703; (c)
Published on 03 October 2013. Downloaded on 14/05/2016 00:48:16.
H. Jiang, A. Falcicchio, K. L. Jensen, M. W. Paixão,
S. Bertelsen and K. A. Jørgensen, J. Am. Chem. Soc., 2009,
131, 7153; (d) T. Wu, J. Yin and G. Liu, J. Am. Chem. Soc.,
2009, 131, 16354; (e) J. Erb, D. H. Paull, T. Dudding,
L. Belding and T. Lectka, J. Am. Chem. Soc., 2011, 133,
7536; (f) P. Kwiatkowski, T. D. Beeson, J. C. Conrad and
D. W. C. MacMillan, J. Am. Chem. Soc., 2011, 133, 1738; (g)
V. Rauniyar, A. D. Lackner, G. L. Hamilton and F. D. Toste,
Science, 2011, 334, 1681; (h) R. J. Phillips, K. Hiramatsu
and F. D. Toste, J. Am. Chem. Soc., 2012, 134, 8376; (i)
N. A. Cochrane, H. Nguyen and M. R. Gagne, J. Am. Chem.
Soc., 2013, 135, 628; (j) F. Sladojevich, S. I. Arlow, P. Tang
and T. Ritter, J. Am. Chem. Soc., 2013, 135, 2470.
4 (a) M. C. Pacheco, S. Purser and V. Gouverneur, Chem. Rev.,
2008, 108, 1943; (b) S. Thibaudeau and V. Gouverneur, Org.
Lett., 2003, 5, 4891; (c) B. Greedy, J. M. Paris, T. Vidal and
V. Gouverneur, Angew. Chem., Int. Ed., 2003, 42, 3291; (d)
S. Thibaudeau, R. Fuller and V. Gouverneur, Org. Biomol.
Chem., 2004, 2, 1110; (e) S. Boldon, J. E. Moore and
V. Gouverneur, Chem. Commun., 2008, 3622.
5 (a) M. H. Katcher and A. G. Doyle, J. Am. Chem. Soc., 2010,
132, 17402; (b) M. H. Katcher, A. Sha and A. G. Doyle, J.
Am. Chem. Soc., 2011, 133, 15902; (c) C. Hollingworth,
A. Hazari, M. N. Hopkinson, M. Tredwell, E. Benedetto,
M. Huiban, A. D. Gee, J. M. Brown and V. Gouverneur,
Angew. Chem., Int. Ed., 2011, 50, 2613; (d) A. M. Lauer and
J. Wu, Org. Lett., 2012, 14, 5138; (e) E. Benedetto,
M. Tredwell, C. Hollingworth, T. Khotavivattana,
J. M. Brown and V. Gouverneur, Chem. Sci., 2013, 4, 89; (f)
C. Xue, X. Jiang, C. Fu and S. Ma, Chem. Commun., 2013,
49, 5651; (g) M.-G. Braun, M. H. Katcher and A. G. Doyle,
Chem. Sci., 2013, 4, 1216.
6 J. J. Topczewski, T. J. Tewson and H. M. Nguyen, J. Am. Chem.
Soc., 2011, 133, 19318.
7 Comprehensive Organic Synthesis, ed. B. M. Trost and I.
Fleming, Pergamon Press, New York, 1991, vol. 6.
8 B. M. Trost and M. L. Crawley, Chem. Rev., 2003, 103,
2921.
9 (a) J. Tsuji, H. Kataoka and Y. Kobaysahi, Tetrahedron Lett.,
1981, 22, 2575; (b) B. M. Trost and G. A. Molander, J. Am.
Chem. Soc., 1981, 103, 5969; (c) B. M. Trost and S. R. Angle,
J. Am. Chem. Soc., 1985, 107, 6123.
This journal is © The Royal Society of Chemistry 2014
View Article Online
Chemical Science
10 Several representative examples, see: (a) B. M. Trost and
A. Tenaglia, Tetrahedron Lett., 1988, 29, 2931; (b)
B. M. Trost, E. J. McEachern and F. D. Toste, J. Am. Chem.
Soc., 1998, 120, 12702–12703; (c) B. M. Trost and
E. J. McEachern, J. Am. Chem. Soc., 1999, 121, 8649–8650;
(d) X.-Q. Yu, F. Yoshimura, F. Ito, M. Sasaki, A. Hirai,
K. Tanino and M. Miyashita, Angew. Chem., Int. Ed., 2008,
47, 750–754.
11 K. Fagnou and M. Lautens, Org. Lett., 2000, 2, 2319.
12 (a) S. Bruns and G. Haufe, J. Fluorine Chem., 2000, 104,
247; (b) G. Haufe, S. Bruns and M. Runge, J. Fluorine
Chem., 2001, 112, 55; (c) G. Hauge and S. Bruns, Adv.
Synth. Catal., 2002, 344, 165; (d) J. A. Kalow and
A. G. Doyle, J. Am. Chem. Soc., 2010, 132, 3268; (e)
J. A. Kalow and A. G. Doyle, J. Am. Chem. Soc., 2011, 133,
16001.
13 J. Zhu, G. C. Tsui and M. Lautens, Angew. Chem., Int. Ed.,
2012, 51, 12353.
14 There are two examples of regioselective opening of vinyl
epoxides with triethylamine trihydrouoride in the
absence of the metal catalyst, see: (a) A. Hedhli and
A. Baklouti, J. Fluorine Chem., 1995, 70, 141; (b) L. Hunter,
D. O’Hagan and A. M. Z. Sawin, J. Am. Chem. Soc., 2006,
128, 16422–16423.
15 To conrm the relative stereochemistry of 2A, it was
converted into allylic benzoate, which underwent
hydrogenation to afford the trans-1,2-uoride whose
relative stereochemistry was conrmed by 1H NMR and
COSY analyses. See ESI† for details.
16 Heating the reaction to 40  C and 60  C in THF resulted in
37% and 30% NMR yield, respectively.
17 Although THF provides uorohydrin 2A in higher NMR
yield than Et2O, use of Et2O as a solvent in rhodium-
catalyzed ring-opening of vinyl epoxide 1 resulted in a
biphasic mixture. This phase separation eliminates the
need for an aqueous workup, and the crude product 2A
was extracted from a biphasic mixture and subsequently
treated with 4-urobenzoyl chloride to form isolable
allylic uoride 2.
18 (a) R. Bittman, N. M. Witzke, T.-C. Lee, M. L. Blank and
F. Snyder, J. Lipid Res., 1987, 28, 733–738; (b) G. Haufe
and A. Burchardt, Eur. J. Org. Chem., 2001, 4501–
4507; (c) A. Burchardt, T. Takahashi, Y. Takeuchi and
G. Haufe, J. Org. Chem., 2001, 66, 2078–2084; (d)
R. Bittman, H.-S. Byun, K. C. Reddy, P. Samadder and
G. Arthur, J. Med. Chem., 1997, 40, 1391–1395.
19 It is known that regioselective opening of enantiopure vinyl
epoxide 11 provided allylic uorohydrin with opposite
stereochemistry.14a
20 See the ESI† for details.
21 This result is consistent with what has been reported for the
rhodium-catalyzed regioselective opening of vinyl epoxides
with alcohols and anilines.11
22 Based on the result obtained with epoxide R-(8) in
Scheme 4b, we hypothesized that vinyl epoxides bearing
the C(1)-substituted group are likely to occur via SN1
mechanism.
Chem. Sci., 2014, 5, 291–296 | 295
 View Article Online

Chemical Science Edge Article

23 For an alternative enylrhodium intermediate, see: P. A. Evans
and J. D. Nelson, J. Am. Chem. Soc., 1998, 120, 5581.
24 R. G. Parr and R. G. Pearson, J. Am. Chem. Soc., 1983, 105,
7512–7516.
Published on 03 October 2013. Downloaded on 14/05/2016 00:48:16.
25 B. M. Trost, T. Zhang and J. D. Sieber, Chem. Sci., 2010, 1,
427.
26 A. Hazari, V. Gouverneur and J. M. Brown, Angew. Chem., Int.
Ed., 2009, 48, 1296.

296 | Chem. Sci., 2014, 5, 291–296 This journal is © The Royal Society of Chemistry 2014