Selectfluor-mediated mild oxidative halogenation and thiocyanation of 1-aryl-allenes with TMSX (X = Cl, Br, I, NCS) and NH4SCN

Article abstract of DOI:10.1016/j.tetlet.2014.02.110

Presence of TMSX (X = Cl, Br, I) unleashes the oxidative character of Selectfluor and provides a mild dihalogenation method for 1-arylallenes. Preference for 2,3-addition was observed with TMSCl in MeCN irrespective of the nature of the substituent on the aryl moiety, whereas 1,2-addition was preferred in [BMIM][BF₄]. With TMSBr and TMSI only products corresponding to 2,3-addition were observed. Reactions carried out with TMSBr in IL solvents gave the corresponding monobromoalkenes as a major product along with the isomeric dibromo-alkenes. Reaction with NH₄SCN provided convenient access to dithiocyanate derivatives. The same products were formed via TMS-NCS/Selectfluor. Formation of common products via TMSNCS and NH ₄SCN points to the formation and interplay of SCN⁺/ NCS⁺ as incipient electrophiles.

Full text of DOI:10.1016/j.tetlet.2014.02.110

Tetrahedron Letters 55 (2014) 2401–2405
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Tetrahedron Letters
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Selectfluor-mediated mild oxidative halogenation and thiocyanation
of 1-aryl-allenes with TMSX (X = Cl, Br, I, NCS) and NH4SCN
a
b
Kenneth K. Laali a, , Ganesh C. Nandi , Scott D. Bunge
⇑
a Department of Chemistry, University of North Florida, 1 UNF Drive, Jacksonville, FL 32224, United States
b Department of Chemistry and Biochemistry, Kent State University, Kent, OH 44242, United States
a r t i c l e i n f o
a b s t r a c t
Article history:
Presence of TMSX (X = Cl, Br, I) unleashes the oxidative character of Selectfluor and provides a mild dihalo-
genation method for 1-arylallenes. Preference for 2,3-addition was observed with TMSCl in MeCN irre-
spective of the nature of the substituent on the aryl moiety, whereas 1,2-addition was preferred in
[BMIM][BF4]. With TMSBr and TMSI only products corresponding to 2,3-addition were observed. Reac-
tions carried out with TMSBr in IL solvents gave the corresponding monobromoalkenes as a major prod-
uct along with the isomeric dibromo-alkenes. Reaction with NH4SCN provided convenient access to
dithiocyanate derivatives. The same products were formed via TMS-NCS/Selectfluor. Formation of com-
mon products via TMSNCS and NH4SCN points to the formation and interplay of SCN+/NCS+ as incipient
electrophiles.
Received 12 February 2014
Revised 25 February 2014
Accepted 26 February 2014
Available online 6 March 2014
Keywords:
1-Arylallenes
TMSX
Selectfluor
Ó 2014 Elsevier Ltd. All rights reserved.
Dihalogenation
Dithiocyanation
MeCN versus IL
In a recent study1 we reported on the reaction of 1-aryl-allenes
with propargylic alcohols in the presence of metallic triflates and
TMSX (X = Cl, Br, N3) and formation of isomeric enzymes by attack
of propargyl cation at the central carbon of allenes and subsequent
trapping of the resulting allyl cations with TMSX. Inspired by a re-
port on fluorohydroxylation of aryl-allenes with Selectfluor in
MeCN/H2O,2 we sought to develop a fluorohalogenation approach
for allenes employing TMSX/Selectfluor, but product analysis with
TMSCl/Selectfluor showed no fluorine incorporation, instead iso-
meric dichloroalkenes were formed. We report here on the efficacy
of this Selectfluor-mediated approach for dihalofunctionalization
and dithiocyanation of 1-aryl-allenes.
Whereas Selectfluor is widely employed for fluoro functionaliza-
tion of organic compounds,3,4 its ability to act as mediator and cat-
alyst for oxidative transformations without fluorination is
relatively less explored. Generation of electrophile equivalents
Cl+, Br+, SCN+, and NO+2 mediated by Selectfluor and their in situ
reactions with aromatics, and bromination of representative al-
kenes with Selectfluor/KBr have previously been reported.5a,b
Selectfluor-mediated thiocyanation of representative heteroarenes
and ketones with NH4SCN have also been demonstrated,6a,b and
the progress in Selectfluor-mediated synthesis has been reviewed.7
More recently, oxyarylation of alkenes8a and hydroxylation of
arenes8bwere reported by a combined use of transition metals
and Selectfluor.
Reactions of 1-aryl-allenes 1a–1d with TMSX (X = Cl, Br, I)
(2 equiv) were investigated at room temperature in the presence
of 1 equiv of Selectfluor. Acetonitrile and imidazolium-ILs were se-
lected as solvents for this study because Selectfluor can be dissolved
in these media.4a,7a Reaction with TMSCl resulted in the formation
of isomeric dichloroalkenes 2 and 3 as major and 4 as minor prod-
ucts, in combined isolated yields ranging from 55% to 78%
(Scheme 1 and Table 1).9 Product ratios observed for 1a in the pres-
ent study using TMSCl/Selectfluor differ from those reported using
TMSCl/[PhCH2NMe3][Cl]/KMnO4, where the dichloroalkene 4a was
a major product (2a:3a:4a = 3:1:6).10 In an early study of halogena-
tion of aryl-allenes with X2 (Cl2, Br2, IBr)11 the 1,2-addition prod-
ucts were found to be major in MeOH at 0 °C, and 2,3-addition
was predominant (>0 °C) in nonpolar media (CS2, CH2Cl2, CCl4).
Rearrangement of the 1,2-adducts to 2,3-adducts was observed
in an NMR tube experiment on increasing temperature (À70 °C
to >0 °C).
Products formed with TMSCl/Selectfluor implies oxidative trans-
formation of ClÀ to >Cl+,12 followed by an electrophilic attack at the
central carbon of the allenyl moiety generating an incipient haloal-
lyl cation, and nucleophilic trapping by ClÀ at the unsubstituted
and substituted termini of the haloallyl moiety.13 The observed
product distributions (Table 1) indicate a clear preference for
nucleophilic attack at the less substituted terminus of the allylic
moiety leading to 2,3-addition, but there is no clear correlation
⇑
Corresponding author. Tel.: +1 904 620 1503; fax: +1 904 620 3535.
E-mail address: kenneth.laali@UNF.edu (K.K. Laali).
http://dx.doi.org/10.1016/j.tetlet.2014.02.110
0040-4039/Ó 2014 Elsevier Ltd. All rights reserved.

2402
K. K. Laali et al. / Tetrahedron Letters 55 (2014) 2401–2405
H
H
H
H
H
Cl
Cl
H
Cl
Cl
Selectfluor (1.0 eq.)
H
+
+
Cl
Cl
R
TMSCl (2.0 eq.)
Acetonitrile
R
R
4
3
2
R
R = H; 1a
R = Me; 1b
1c
2a
2b
2c
2d
3a
3b
3c
3d
4a
4b
4c
4d
R = H
R = Me
R = F
25 oC, 5h
R = F;
R = Cl; 1d
R = Cl
Scheme 1. Oxidative dichlorination of 1-aryl-allenes with TMSCl/Selectfluor in MeCN.
Table 1
Table 2
Yields and product distributions in oxidative dichlorination of 1-aryl-allenes with
Yields and product distributions in oxidative dichlorination of 1-aryl-allenes with
TMSCl/Selectfluor in MeCN
TMSCl/Selectfluor in [BMIM][BF4]
Entry
Allene
Yielda (%)
2b:3c:4c
Entry
Allene
Yielda (%)
2:3:4:5
1
2
3
4
1a
1b
1c
1d
68
55
70
78
44:40:16
53:47:0
40:33:27
27:30:33
1
2
3
4
1a
1b
1c
1d
55
52
58
61
13:19:68:0
25:13:26:26
16:17:51:16
16 16:66:0
a
b
c
a
Total isolated yield.
Isolated yield.
Total yield of crude reaction mixture; product ratios were estimated by NMR.
Compounds 3 and 4 were isolated as a mixture and NMR ratios were used to
determine their respective isolated yields.
H
H
H
H
H
Br
2.0 equiv TMSBr
1.0 equiv Selectfluor
Br
Br
+
Br
with regard to substituent effects (1a–1d). Interestingly when the
same reactions were carried out in [BMIM][BF4] as solvent signifi-
cantly increased formation of the dichloroalkenes 4 was observed,
and in addition the monochloroalkene 5 was formed as a minor
product with allenes 1b and 1c (Scheme 2 and Table 2). Increased
formation of compound 4 may be attributed to differences in ion-
pairing and solvation effect between IL and MeCN, and increased
haloallylic cation character in the IL solvent.14
R
Acetonitrile
7
6
R
RT, 20-30 min
R
R = H; 1a; R = Me; 1b
R = F; 1c; R = Cl; 1d
Scheme 3. Oxidative dibromination of allenes with TMSBr/Selectfluor in MeCN.
Table 3
Focusing on oxidative bromination, 1-aryl-allenes 1a–1d were
reacted with TMSBr/Selectfluor in MeCN to give the isomeric dib-
romoalkenes 6 and 7 in roughly 1:1 ratio, and typically in better
than 70% combined yields (Scheme 3 and Table 3). In this case
the 1,2-addition products were not detected. A different product
distribution was observed in [BMIM][BF4] as solvent. Apart from
isomeric 6 and 7 the corresponding monobromoalkene 8 was
formed as major product (Scheme 4 and Table 4). The cinnamyl
bromides 8 were quickly transformed into cinnamyl alcohols
during silica-gel chromatography. Products 8 and 5 correspond to
formal addition of HX, and were only observed when ILs were used
as solvent. Formation of 8 as a major product was also observed in
[BMIM][PF6] and [BMIM][NTf2] in control experiments using
aryl-allene 1a. Product ratios (6b:7b:8b) in [BMIM][PF6] and in
[BMIM][NTf2] were 9:7:85 and 3:2:95, respectively. Competing
formation of 8 may be attributed to possible presence of H3O+ or
HBF4 in [BMIM][BF4] but this seems less likely given that the same
results were observed in two other freshly prepared ILs and it
seems more plausible that HX originated from hydrolysis of TMSX
by adventitious moisture.
Yields and product distributions in oxidative dibromination of 1-aryl-allenes with
TMSBr/Selectfluor in MeCN
Entry
Allene
Yielda (%)
6
7
1
2
3
4
1a
2a
3a
4a
34 (6a)
31 (6b)
34 (6c)
35 (6d)
37 (7a)
27 (7b)
38 (7c)
38 (7d)
a
Isolated yield.
Moving onto oxidative iodination, 1-aryl-allenes 1a–1d reacted
with TMSI/Selectfluor in MeCN to give the isomeric di-iodoalkenes
9 and 10 in 1:1 ratio in respectable isolated yields (Scheme 5a and
Table 5a). Interconversion of the diiodo isomers 9 and 10 was ob-
served during silica gel chromatography. These isomers also
underwent aerial oxidation to the alcohol 11 and the aldehyde
12 (Scheme 5b).
There have been only limited earlier studies on Selectfluor-med-
iated thiocyanation,6a,b,7b and the potential of this method for
H
H
H
H
H
H
Cl
Cl
H
Cl
Cl
Cl
Selectfluor (1.0 eq.)
H
+
+
+
H
Cl
Cl
TMSCl (2.0 eq.)
[BMIM][BF4]
25 oC, 48h
R
R
R
5
4
3
R
2
R
1a
2a
2b
2c
2d
3a
3b
3c
3d
4a
4b
4c
4d
5a
5b
5c
5d
R = H;
R = H
R = Me
R = F
R = Me; 1b
R = F; 1c
1d
R = Cl;
R = Cl
Scheme 2. Oxidative dichlorination of 1-aryl-allenes with TMSCl/Selectfluor in [BMIM][BF4].

K. K. Laali et al. / Tetrahedron Letters 55 (2014) 2401–2405
2403
H
H
H
H
H
Br
TMSBr (2.0 eq.)
Br
Br
Br
Selectfluor (1.0 eq.)
+
R
+
R
Br
7
8
[BMIM][BF4]
R
6
RT, 20-30 min
R
R = H; 1a
R = H
6a
7a
7b
7c
7d
8a
8b
8c
8d
R = Me; 1b
R = F; 1c
R = Cl; 1d
R = Me 6b
R = F
6c
6d
R = Cl
Scheme 4. Oxidative dibromination of 1-aryl allenes with TMSBr/Selectfluor in [BMIM][BF4].
Table 4
oxidative dithiocyanation of allenes has not been explored. Reac-
tion of 1-aryl-allenes 1a–1d with NH4SCN/Selectfluor in MeCN at
room temperature resulted in slow formation of two isomeric
2,3-disubstituted derivatives in relatively modest isolated yields
(only trace amounts in the cases of 1d). Prolonged mixing at room
temperature followed by stirring at 50 °C did not improve the con-
versions. Further studies, aided in particular by differences in their
13C NMR and IR spectra (Supplemental data) showed that whereas
the major isomer was the dithiocyanate derivative 13, the minor
Yields and product distributions in oxidative dibromination of 1-aryl-allenes with
TMSBr/Selectfluor in [BMIM][BF4]
Entry
Allene
Yielda (%)
6:7:8
1
2
3
4
1a
1b
1c
1d
94
95
98
93
9:12:79
4:3:93
2:2:96
18:18:64
a
Total yield of crude reaction mixture; product ratios were determined by NMR.
isomer was
a mixed NCS/SCN disubstituted compound 14
(Scheme 6 and Table 6). Relative stereochemistry of 13 as E and
14 as Z was decided based on NOE data.
H
H
I
Surprisingly, the same products were formed when allenes 1a–
1d were allowed to react with TMS-NCS/Selectfluor (Scheme 7 and
Table 7). The TMS-NCS reactions proved more efficient and re-
sulted in better isolated yields. It is noteworthy that similar to
reactions with TMSBr and TMSI a product corresponding to nucle-
ophilic attack by SCN- at the substituted terminus of the allylic
moiety was not observed. Crystals suitable for X-ray analysis were
obtained from 13b and 13c from CH2Cl2/hexane at À20 °C. Thermal
ellipsoid plots for 13b and 13C (Figs. 1a and 1b) confirm the E con-
figuration at the double-bond, in agreement with the NOE-based
correlations.9 Unfortunately the SCN/NCS derivatives 14b, 14c,
and 14d were oils and would not crystallize. Compound 14a was
obtained as solid but did not produce good crystals.
I
I
H
H
H
TMSI (2.0 eq.)
+
Selectfluor (1.0 eq.)
I
R
R
9
10
Acetonitrile
25 oC, 3 mins
R = H; 9a
R = Me; 9b
R = F; 9c
R = Cl; 9d
10a
10b
10c
10d
R = H; 1a
R = Me; 1b
R = F; 1c
R = Cl; 1d
R
Scheme 5a. Oxidative diiodination of 1-aryl-allenes with TMSI/Selectfluor in MeCN.
Table 5a
Yields and product distributions in oxidative diiodination of 1-aryl-allenes with TMSI/
Selectfluor in MeCN
Table 6
Entry
Allene (1)
Yielda (%)
9:10
Yields and product distributions in reaction of 1-arylallenes with NH4SCN/Selectfluor
1
2
3
4
1a
1b
1c
1d
68
63
70
67
1:1
1:1
54:46
56:44
Entry
Allene
Yielda (%)
13
14
1
2
3
4
1a
2a
3a
4a
27
26
22
tr
11
19
8
a
Isolated yields for 9+10; isomers ratios from NMR.
tr
a
Isolated yield; tr: trace.
H
H
H
OH
H
I
CHO
I
I
Air
+
+
I
I
I
R
R
R
11
12
R
9
10
Scheme 5b. Aerial oxidation of the diiodo compounds.
H
H
SCN
H
H
H
SCN
SCN
NH4SCN (2.0 equiv)
+
Selectfluor (1.0 equiv)
MeCN, r.t, 48 h
NCS
R
R
14
13
R = H;
R = Me;
R = F;
13a
13b
13c
14a
14b
14c
R = H; 1a
R
1b
R = Me;
R = F; 1c
R = Cl; 1d
R = Cl;
(gave only traces of 13 and 14)
Scheme 6. Reaction of 1-arylallenes with NH4SCN/Selectfluor.

2404
K. K. Laali et al. / Tetrahedron Letters 55 (2014) 2401–2405
H
H
SCN
H
H
H
SCN
SCN
TMSNCS (2.0 equiv)
+
Selectfluor (1.0 equiv)
MeCN, r.t, 5h
NCS
R
R
14
13
R = H;
13a
14a
14b
14c
14d
R = H; 1a
R = Me; 1b
R = F; 1c
R = Cl; 1d
R = Me; 13b
R
R = F;
13c
13d
R = Cl;
Scheme 7. Reaction of 1-arylallenes with TMS-NCS/Selectfluor.
Table 7
Cl
Yields and product distributions in reaction of 1-arylallenes with TMSNCS/Selectfluor
Cl
Cl
Cl
N
2BF4
Entry
Allene
Yielda (%)
N
N
N
F
After ?
2X
N
N
H
13
14
before
1
2
3
4
1a
1b
1c
1d
41
39
40
29
22
19
23
15
(i)
(iii)
(ii)
Scheme 8. Insight into the structure of ‘spent’ Selectfluor.
a
Isolated yield.
1-arylallenes in the presence of TMSX (X = Cl, Br, I, NCS) and NH4-
SCN is demonstrated. The observed products may be rationalized
by electrophilic attack of ‘X+’ and ‘SCN+’ at the central carbon of al-
lenes to form incipient allylic cations that are preferentially
quenched at the unsubstituted (less sterically crowded) terminus
of the allylic moiety to furnish the 2,3-adducts. The 1,2-addition
products were only observed with TMSCl. These products in-
creased when [BMIM][BF4] was used as solvent. Quenching at the
substituted terminus of the allylic moiety and/or halonium ion for-
mation could account for the 1,2-adducts. The observed regioselec-
tivity differences in MeCN and in IL may be due to differences in
solvation and ion pairing effects. Formation of common dithiocya-
nate derivatives 13 and 14 via TMSNCS/Selectfluor and NH4SCN/
Selectfluor implies the formation and interplay of SCN+/NCS+ as
incipient electrophiles. Comparative NMR study suggests that
‘spent’ Selectfluor is an N-protonated dication salt.15 Further studies
Finally in an effort to understand how Selectfluor is transformed
in these reactions (Scheme 8 and Supplementary data) NMR spec-
tra of ‘spent’ Selectfluor (the solid formed in the reaction upon addi-
tion of TMSX and collected after completion of the reaction) (see
Supplemental file) were compared with: (a) an authentic sample
of Selectfluor (i); (b) an authentic sample of the monocation salt
(ii) synthesized by refluxing DABCO in CH2Cl2; and (c) the dication
(iii) generated by protonation of (ii) with TFAH (X = CF3COÀ2 ). Based
on this comparison (Suppl. data) it may be concluded that
Selectfluor (i) is transformed into dication salt iii (the source of
H+ is likely hydrolysis of TMSX).
In summary the potential of Selectfluor to act as mediator and
oxidant for mild dihalogenation and dithiocyanation of
Figure 1a. Thermal ellipsoid plot for 13b.
Figure 1b. Thermal ellipsoid plot for 13c.

K. K. Laali et al. / Tetrahedron Letters 55 (2014) 2401–2405
2405
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Lett. 2002, 43, 6573–6575; (d) Heravi, M. R. P. J. Fluorine Chem. 2008, 129, 217–
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2002, 67, 4487–4493; (b) Ye, C.; Shreeve, J. M. J. Org. Chem. 2004, 69, 8561–
8563.
aimed at gaining deeper understanding of the mechanistic aspects
of these transformations are called for.16
Acknowledgment
We thank the University of North Florida for research support.
6. (a) Yadav, J. S.; Reddy, B. V. S.; Reddy, Y. J. Chem. Lett. 2008, 37, 652–653; (b)
Wu, D.; Yang, X.; Yang, L.; Wu J. Chem. Sci. 2012, 124, 901–905.
7. (a) Stavber, S.; Zupan, M. Acta. Chim. Slov. 2005, 52, 13–26; (b) Stavber, S.
Molecules 2011, 16, 6432–6464.
8. (a) Ball, L. T.; Green, M.; Lloyd-Jones, G. C.; Russell, C. A. Org. Lett. 2010, 12,
4724–4727; (b) Yang, Y.; Lin, Y.; Rao, Y. Org. Lett. 2012, 14, 2874–2877.
9. The E and Z assignments were based on magnitude of allylic coupling and were
verified in selected cases by NOE (see Experimental).
10. Boyes, A. L.; Wild, M. Tetrahedron Lett. 1998, 39, 6725–6728.
11. Okuyama, T.; Ohashi, K.; Izawa, K.; Fueno, T. J. Org. Chem. 1974, 39, 2255–2258.
12. The E1/2 (V, SCE) for Selectfluor is 0.33 (see Ref. 7a) as compared to À1.33 for ClÀ
to >Cl2.
13. It is conceivable that the 1,2-adduct is also formed via a cyclic halonium ion (as
suggested in Ref. 11).
Supplementary data
Supplementary data (experimental section and selected 1H,
13C{1H}, and 19F (as applicable) NMR and IR spectra for the prod-
ucts. CCDC 954949-954950 contains the supplementary crystallo-
graphic data for this paper. These data can be obtained free of
charge from The Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif) associated with this article
can be found, in the online version, at http://dx.doi.org/10.1016/
j.tetlet.2014.02.110.
14. Alternatively this could stem from increased lifetime of the halonium ion
intermediate in IL solvent.
References and notes
15. These observations imply that recycling and reuse of Selectfluor may be feasible
in large scale operations by recovery of the dication salt (iii) and subsequent
deprotonation/N-fluorination.
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16. Reaction of 1c with Selectfluor/TMSCl was performed in an NMR scale
experiment in CD3CN in an effort to determine if 4C is formed first and
subsequently rearranges to 3c/2c. Signals due to all 3 products were detected
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