The anionic thia-Fries rearrangement of aryl triflates

Article abstract of DOI:10.1039/b210648e

Aryl triflates undergo LDA-mediated rearrangement to generate o-hydroxyaryl trifluoromethylsulfones. In some cases, partitioning between rearrangement and aryne generation can be controlled.

Full text of DOI:10.1039/b210648e

The anionic thia-Fries rearrangement of aryl triflates
Jonathan P. H. Charmant,a Alan M. Dykeb and Guy C. Lloyd-Jones*b
a Structural Chemistry Laboratory, School of Chemistry, Cantock’s Close, Bristol, UK
b Bristol Centre for Organometallic Catalysis, Cantock’s Close, Bristol, UK.
E-mail: guy.lloyd-jones@bris.ac.uk; Fax: 44 117 929 861; Tel: 44 117 928 8165
Received (in Cambridge, UK) 30th October 2002, Accepted 17th December 2002
First published as an Advance Article on the web 14th January 2003
Aryl triflates undergo LDA-mediated rearrangement to
generate o-hydroxyaryl trifluoromethylsulfones. In some
cases, partitioning between rearrangement and aryne gen-
eration can be controlled.
In contrast to double defunctionalisation methods to arynes
from o-Z-Ar-X,1 the base-mediated elimination of ‘HX’ from
Scheme 1 Anionic thia-Fries rearrangement of triflate 1.
haloarenes (Ar-X) requires only a single functional group and
has been explored extensively.2 The use of pseudohalides was
pioneered by Fleming who generated benzynes from aryl
benzenesulfonates with the sterically hindered base Li-TMP.3
However, the yields in these reactions were compromised by
ortho-metallation of the benzene sulfonyl chloride derived
ring.† Subsequently, Scott and Wickham4 introduced the use of
aryl triflates5 which cannot undergo such side reactions.
Employing LDA, generated in situ by reaction of BuLi (2
equiv.) with an excess of N,N-diisopropylamine (DIPA) in THF
or DME as solvent, aryl triflates underwent elimination and
gave anilines in good yield by trapping, in situ,6 with DIPA.4,7
Herein, we report that aryl triflates also undergo a competing
anionic thia-Fries rearrangement. To the best of our knowledge
this is unprecedented,8 however, it may have been overlooked
since such reactions are normally quenched with water and the
base-soluble phenolic components not extracted or ana-
lysed.4,7
We recently attempted a Pd-catalysed cross-coupling of
1-chloro-2-naphthalene triflate 19 with a pyridyl zinc halide,
generated in situ using LDA/ZnCl2.10 A side product of the
reaction was ultimately identified as 2, the product of a thia-
Fries rearrangement of 1. Further experiments revealed that
LDA mediates rearrangement and under simpler conditions (1.0
equiv. LDA, THF, 278 °C to RT) 2 is obtained from 1 in 64%
yield after aqueous work-up, Scheme 1, Table entry 1.
LiHMDS gave 2 in lower yield (48%) and other bases such as
Li-TMP, sec-BuLi/TMEDA or BuLi were not effective.
Confirmation that a thia-Fries rearrangement occurs was
obtained by single crystal X-ray diffraction of 4‡ Scheme 2.
In light of the work of Scott and Wickham,4,7 we were
curious that naphthyne derived aniline-type products were not
obtained from 1, as might be expected. We therefore tested
other aryl triflates under analogous conditions, Table 1 (except
entries 4, 5 and 9).
Table 1 Elimination versus anionic thia-Fries rearrangement of aryl
triflates
ArOTf
Entry Ar =
Yielda
(%)
Mole fractionb
ArN(i-Pr)2 o-Ar(OH)Tf
ArOH ArH
1-Cl-2-naphthyl
(1)
1-Br-2-naphthyl 49
2-Cl-phenyl (5) 80
2-Cl-phenyl (5) 65d
2-Cl-phenyl (5) 59e
3-Cl-phenyl
4-Cl-phenyl
2-naphthyl (8)
2-naphthyl (8)
1-naphthyl
phenyl
4-biphenyl
4-tolyl
2-anisyl
3-anisyl
4-anisyl
c
c
c
c
c
c
c
c
c
c
c
c
c
c
c
c
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
64
—
—
—
1.00 (2)
1.00
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
c
c
1.00 (6)
c
c
c
Scheme 2 The single crystal X-ray structure (protons omitted for clarity) of
the 2,2A-dihydroxy-3,3A-disulfone 4, the product of a double anionic thia-
Fries rearrangement of 2,2A-bis triflate 3.
1.00 (7)d
—
—
—
c
—
1.00
0.31
85
72
67
74i
46
68
56
59
95
60
99
0.69f
0.64g
0.36
—
c
1.00h (9)
—
—
c
c
A clear differentiation was found between those substrates
bearing an electron withdrawing group ortho to the triflate
(entries 1–3) which exclusively undergo anionic thia-Fries
rearrangement and those with an electron donating group
(entries 13–16) which exclusively undergo benzyne genera-
tion.
0.59i (9) 0.41e (10)
—
c
1.00j
1.00
—
—
—
—
—
—
—
—
c
c
c
c
c
c
c
c
c
—
0.71k
1.00l
1.00m
1.00n
1.00n
—
0.29
c
c
c
—
—
c
c
—
—
The conditions employed differ substantially from those
developed by Scott and Wickham where 2 equiv. LDA was
employed in the presence of a large excess of DIPA (10–140
equiv.). The latter was present to ensure rapid capture of the
aryne and thereby avoid arene co-products.4 What emerges
from our study is that both DIPA and THF also have a profound
influence at an earlier stage of reaction. The effect of THF is
evident with substrates that bear electron withdrawing groups
and tend to rearrange. For example, o-chlorophenyl triflate (5)
undergoes rearrangement to give sulfone (6) as the exclusive
non-polymeric product when reacted with LDA in THF (entry
3) but gives the mono and bis-anilines (7, 65%), with no trace of
6 when DIPA is employed as solvent. (Table 1, entry 4; Scheme
3).4 However, when the same reaction is conducted in DIPA
c
c
—
—
c
c
—
—
a Reaction conditions (except for entries 4, 5 and 9): 1.04 DIPA + 1.00 BuLi
in THF at 278 °C to RT (1h) then cooled to 278 °C, ArOTf added, reaction
warmed to RT over 10 mins. then stirred o/n and quenched with water.
Combined yield of pure materials separated by column chromatography on
silica-gel. b Based on isolated yields. In no case, except entry 5, was
substrate (ArOTf) recovered unreacted. Material balance: polymers. c 53%
(not detected by tlc analysis). d DIPA as solvent (125 equiv.) with 2.0 LDA;
product m-chloro aniline/1,3-bis-aniline (7/3). e Triflate 5 heated to 240 °C
(microwave) in DMF for 10 min. Material balance unreacted 5. f m-Chloro
h
aniline/1,3-bis-aniline (3/1). g m/p 28/72. a/b 16/84. i 1.10 equiv. BuLi
employed. j a/b 28/72. k m/p 55/45. l m/p 37/63. m > 98% m isomer. n m/p
27/73.
380
CHEM. COMMUN., 2003, 380–381
This journal is © The Royal Society of Chemistry 2003

containing as little as 4% THF, rearrangement to 6 competes
extensively (40%).
readily undergo an anionic thia-Fries rearrangement on reaction
with LDA in the presence of THF to give o-hydroxyaryl
trifluoromethylsulfones rather than generating arynes. The
analogous thermal process does not proceed readily. The ready
orthometallation of arylsulfones make the rearrangement prod-
ucts of interest for further elaboration. With substrates that
undergo partitioning between both processes, conducting the
reaction under conditions in which the concentration of excess
DIPA is low favours the anionic thia-Fries rearrangement. The
mechanism by which the (formal) elimination of LiOTf and
competing anionic thia-Fries rearrangement occur is the subject
of an ongoing isotopic labelling, kinetic and computational
study which will be reported in full in due course.17
Scheme 3 Conditions: i, LDA, THF 278 °C to RT then H2O; ii, LDA, DIPA
278 °C to RT then H2O.
The effect of DIPA becomes evident with substrates that are
more delicately balanced with respect to elimination versus
rearrangement. It should be noted that in reactions without
excess DIPA (most entries in Table), there are two complicating
factors. Firstly, aniline formation from the aryne consumes
DIPA. Secondly, aryl deprotonation by LDA (in principle)
generates DIPA. For example, 2-naphthyl triflate (8) gives N,N-
diisopropyl-1/2-naphthylamines (9) as the exclusive non-
polymeric products when reacted with 1.0 equiv. LDA in THF
(67% total yield, Table 1, entry 8). However, addition of 10
mol% BuLi (Table, entry 9), which can deprotonate liberated
DIPA, results in the anionic thia-Fries rearrangement competing
significantly (30% isolated yield of 10, Scheme 4.).§
AMD thanks the EPSRC for support. GCL-J gratefully
acknowledges the RSC for unrestricted funding through the
Hickinbottom Fellowship. We thank Dr J. N. Harvey and
Professor T. C. Gallagher for valuable discussion.
Notes and references
† Di-and tri-benzothiophen dioxides are generated by single or double
insertion of benzyne then cyclisation with loss of PhOLi.
‡ Sequential addition of LDA (2 3 1 equiv., 278 °C to RT) results in step-
wise rearrangement, via [2-(OLi)-3-(CF3SO2)-2A-(OTf)-1,1A-binaphtha-
lene], to give 4 as the only non-polymeric product. Simultaneous twofold
addition gives mixtures.
§ Larger excesses of BuLi result in competing reactions. With 100 mol%
BuLi, naphthalene (30%) is the sole non-polymeric product.
¶ For example, triflate 1 reacts with 10 mol% LDA and 90 mol% BuLi to
give 1/2 in a 90/10 ratio.
∑ Whether aryne generation proceeds via ortho-metallation (E1cb-like) or
direct elimination (E2-like) is the subject of ongoing study.
** In DMF solution, careful heating to 235–240 °C by microwave resulted
in o-chlorophenol. In all cases heating above 250 °C resulted in
decomposition to an uncharacterisable tar.
1 For leading references see: P. C. Buxton, M. Fensome, H. Heaney and
K. G. Mason, Tetrahedron, 1995, 51, 2959.
2 For leading references see: M. Uchiyama, T. Miyoshi, Y. Kajihara, T.
Sakamoto, Y. Otani, T. Ohwada and Y. Kondo, J. Am. Chem. Soc.,
2002, 124, 8514.
Scheme
4 The effect of catalytic BuLi on the anionic thia-Fries
rearrangement of triflate 8 and the contrasting regioselectivity of the
thermal thia-Fries rearrangement of tosylate 11.
3 I. Fleming and M. Talat, J. Chem. Soc., Perkin Trans 1, 1976, 1577.
4 P. P. Wickham, K. H. Hazen, H. Guo, G. Jones, K. H. Reuter and W. J.
Scott, J. Org. Chem., 1991, 56, 2045.
Conducting the same reaction (10 mol% BuLi) in the
presence of the aryne trap diphenylisobenzofuran (which
bypasses the depletion of liberated DIPA) results in quantitative
aryne generation (99% isolated yield of the 1,2- and 2,3-naph-
thyne cycloadducts) and no thia-Fries product 10. BuLi alone is
not effective (triflate 8 is recovered together with varying
quantities of 2-naphthol) and catalytic quantities of DIPA with
1.0 equiv. BuLi do not suffice,¶ perhaps because the DIPA
complexes the lithium o-sulfonyl phenoxide rearrangement
product. Overall the results strongly implicate DIPA in
mediating elimination or inhibiting rearrangement.∑
5 (a) For earlier use of aryl triflates as aryne pre-cursors see: Y.
Himeshima, T. Sonoda and H. Kobayashi, Chem. Lett., 1983, 1211; (b)
K. Shankaran and V. Snieckus, Tetrahedron Lett., 1984, 25, 2827.
6 Heteroaryl lithium species were also employed as in situ traps: K. H.
Reuter and W. J. Scott, J. Org. Chem., 1993, 58, 4722.
7 P. P. Wickham, K. H. Reuter, D. Senanayake, H. Guo, M. Zalesky and
W. J. Scott, Tetrahedron Lett., 1993, 34, 7521.
8 The reaction is somewhat related to the Closson-Hellwinkel rearrange-
ment of biarylsulfonamides, which requires lithiation of both aromatic
rings—see J. J. Eisch, Y. Qian and C. S. Chiu, J. Org. Chem., 1996, 61,
1392.
9 J. P. H. Charmant, I. A. Fallis, N. J. Hunt, G. C. Lloyd-Jones, M. Murray
and T. Nowak, J. Chem. Soc., Dalton Trans, 2000, 1723.
10 G. Karig, N. Thasana and T. Gallagher, Synlett, 2002, 808.
11 The photo-thia Fries rearrangement has been reported: K. Pitchumani,
M. C. D. Manickam and C. Srinivasan, Indian J. Chem., Sect B, 1993,
32, 1074.
12 For analogous processes see: M. E. Jung and T. I. Lazarova,
Tetrahedron Lett., 1996, 37, 7; G. A. Benson, P. J. Maughan, D. P.
Shelly and W. J. Spillane, Tetrahedron Lett., 2001, 42, 8729; F. M.
Moghaddam, M. G. Dekamin and M. Ghaffarzadeh, Tetrahedron Lett.,
2001, 42, 8119.
The thermal11 thia-Fries rearrangement of diaryl sulfo-
nates,12 which gives both ortho and para isomers, is promoted
by Brønsted and by Lewis acids, e.g. HF,13 AlCl3,14 acidic
clays,15 and dry supports (AlCl3/ZnCl2/silica-gel).16 The an-
ionic thia-Fries rearrangement proceeds under markedly differ-
ent conditions (low temperature basic medium) and un-
doubtedly proceeds via a different mechanism, giving only the
ortho-rearranged product. Furthermore, the two processes can
be regio-complementary, for example 2-naphthyl triflate (8)
gives the 3-sulfonyl isomer (10) whereas under the microwave/
acidic conditions, 2-naphthyl tosylate (11) gives the 1-sulfonyl
isomer (12), Scheme 4.16 In stark contrast to anionic conditions
(Table 1 entry 3), o-chlorophenyl triflate (5) fails to rearrange
on heating (oil bath or microwave) neat, in solution (Table 1,
entry 5) or on a Lewis acidic support **
13 J. H. Simon, S. Archer and D. I. Randall, J. Am. Chem. Soc., 1940, 62,
485.
14 V. Baliah and M. Uma, Rec. Trav. Chim. Pays-Bas, 1961, 80, 139.
15 C. Venkatachalapathy and K. Pitchumani, Tetrahedron, 1997, 53,
17171.
16 F. M. Moghaddam and M. G. Dakamin, Tetrahedron Lett., 2000, 41,
3479.
In summary, aryl triflates bearing moderately electron
withdrawing substituents, especially at an ortho-position,
17 A. M. Dyke, J. N. Harvey, A. J. Hester and G. C. Lloyd-Jones,
unpublished results.
CHEM. COMMUN., 2003, 380–381
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