Scheme 1. Direct Formation of Aryl Lactones via the Selective
C-H Abstraction
Table 1. Influence of Oxidants and Additives
time yield
(h)
(%)c
entry
oxidanta
additiveb
conditions
1
2
3
4
5
6
7
8
9
PIDA or PIFA none
CH2Cl2, rt
CH2Cl2, rt
CH2Cl2, rt
24 nrd
69
PIDA
PIDA
PIDA
PIDA
PIFA
HTIB
DMPh
1
KBr
7
KBre
24 65
24 ndf
24 nd
24 <5g
20 25
24 39
Bu4N+Br- CH2Cl2, rt
TMSBr
KBr
KBr
KBr
our ongoing study on hypervalent iodine(III) chemistry, we
have decided to start our survey toward utilization of the
reagents for mild and selective sp3 C-H functionalization,7
aiming at the synthesis of the important lactone compounds.
Thus, initial investigation for the direct γ-lactone formation
was carried out with simple carboxylic acid 2a. Single use
of hypervalent iodine(III) oxidantssspecifically, PhI(OAc)2
(PIDA) or PhI(OCOCF3)2 (PIFA)sdid not give the lactone
3a at all, and no conversion of 2a was observed (Table 1,
entry 1). Activation of PIDA and PIFA with a Lewis acid
such as BF3‚Et2O and TMSOTf did not afford any lactone
3a either, and instead ring oxidation of 2a occurred in these
cases giving rise to complex product mixtures. We next tried
to use other activation methods on the basis of our previous
reports,8 and thus the reaction of 2a with PIDA in the
presence of inorganic bromides8,9a,b was examined. Although
the previous method itself did not induce selective formation
of 3a, use of KBr in organic solVents dramatically altered
the situations; the reaction of 2a with the combination of
PIDA and finely powdered KBr in degassed dichloromethane
afforded lactone 3a in a good yield at room temperature
(entry 2). It should be noted that the added KBr worked as
a catalyst, since it is hardly soluble in CH2Cl2, and for the
most part was present as the precipitate throughout the
reaction. Indeed, catalytic use of KBr slightly affected the
yield of 3a (entry 3). Interestingly, only KBr was suitable
as an effective bromide source,10 and organic bromides,
CH2Cl2, rt
CH2Cl2, rt
CH2Cl2, rt
CH2Cl2, rt
CH2Cl2, rt
benzene, 50 °C 24 nr
AcOEt/H2O
(1/2), rt
KBr
none
8
80 (91)i
10 DDQj
k
11 NaBrO3
NaHSO3
18 15l
a 1.2 equiv of oxidants was used. b 1 equiv relative to 2a. c Isolated yields
based on 2a used. d nr ) no reaction. e 0.5 equiv. f nd ) not detected.
g Determined by 1H NMR observation. h DMP ) Dess-Martin periodinane.
i Isolated yield based on consumed 2a. j DDQ ) 2,3-dichloro-5,6-dicyano-
1,4-benzoquinone. k 1.2 equiv of NaHSO3 was used. l 3-Benzoylpropionic
acid was obtained as a major product.
Bu4N+Br- 9c,d or TMSBr,9e did not give the desired 3a
(entries 4 and 5). In our screening of the oxidants, we have
discovered an alternative appropriate oxidant, p-anisiodine-
(III) diacetate 1, having milder reactivity than PIDA (entries
6-9). As a comparison, we examined the oxidations using
other types of organic or inorganic oxidants, i.e., DDQ4 or
11
NaBrO3 with 2a, but no reaction or undesired ketone
formation11b was observed in these cases (entries 10 and 11).
Having established the optimum reaction conditions, we
then investigated the influence of the nature of the starting
carboxylic acids 2 on the reaction.12 Accordingly, the
γ-lactone forming reactions of para-substituted aryl butyric
acids 2b-f were examined (Table 2). As shown in entry 2,
the presence of an electron donating group allowed the
reaction to proceed to the formation of the corresponding
γ-lactone 3b in good yield. In contrast, the reaction
(6) For recent reviews: (a) Stang, P. J.; Zhdankin, V. V. Chem. ReV.
1996, 96, 1123. (b) Kita, Y.; Takada, T.; Tohma, H. Pure Appl. Chem.
1996, 68, 627. (c) Varvoglis, A. HyperValent Iodine in Organic Synthesis;
Academic Press: San Diego, CA, 1997. (d) Kitamura, T.; Fujiwara, Y.
Org. Prep. Proced. Int. 1997, 29, 409. (e) Ochiai, M. In Chemistry in
HyperValent Compounds; Akiba, K., Ed.; Wiley-VCH: New York, 1999;
Chapter 12. (f) Zhdankin, V. V.; Stang, P. J. Chem. ReV. 2002, 102, 2523.
(g) HyperValent Iodine Chemistry; Wirth, T., Ed.; Springer-Verlag: Berlin,
Germany, 2003. (h) Moriarty, R. M. J. Org. Chem. 2005, 70, 2893. (i)
Wirth, T. Angew. Chem., Int. Ed. 2005, 44, 3656.
(7) Benzylic azidation of phenyl ethers with phenyliodine bis(trifluoro-
acetate): Kita, Y.; Tohma, H.; Takada, T.; Mitoh, S.; Fujita, S.; Gyoten,
M. Synlett 1994, 427.
(8) Generation and detection of active iodine(III)-Br species in water
by the combination of PIDA or iodosobenzene with KBr, see: (a) Tohma,
H.; Takizawa, S.; Maegawa, T.; Kita, Y. Angew. Chem., Int. Ed. 2000, 39,
1306. (b) Tohma, H.; Maegawa, T.; Takizawa, S.; Kita, Y. AdV. Synth.
Catal. 2002, 344, 328.
(10) In Group 1 alkali metal bromide, yield of 2a decreased in order
with KBr > NaBr . LiBr. LiBr induced remarkable bromination at both
aromatic and benzyl carbons.
(11) (a) Hayat, S.; Atta-ur-Rahman; Choudhary, M. I.; Khan, K. M.;
Bayer, E. Tetrahedron Lett. 2001, 42, 1647. (b) Kikuchi, D.; Sakaguchi,
S.; Ishii, Y. J. Org. Chem. 1998, 63, 6023.
(12) Representative experimental procedure: In a flame-dried two-
necked round-bottomed flask, under nitrogen, the iodine(III) reagent 1 (211
mg, 0.6 mmol) was added to a stirred suspension of 4-pheyl butyric acid
2a (82 mg, 0.5 mmol) and KBr (60 mg, 0.5 mmol) in dry CH2Cl2 (5 mL)
then the mixture was vigorously stirred for 8 h at 30 °C. After checking
the reaction completion by TLC, saturated aq NaHCO3 was added to the
mixture, which was then stirred for an additional 5 min. The organic layer
was separated, washed with saturated aq NaHCO3and dilute aq sodium
thiosulfate, and dried over anhydrous Na2SO4. After removal of the solvents,
the residue was subjected to silica gel column chromatography (eluents:
n-hexane/AcOEt) to give the γ-phenyl γ-butyrolactone 3a (65 mg, 80%)
as a white powder. Unreacted 2a (9.8 mg, 12%) was recovered from the
combined aqueous phase by extraction of dichloromethane after acidifying
the solution.
(9) Iodine(III) oxidations in the presence of bromide. LiBr or NaBr: (a)
Braddock, D. C.; Cansell, G.; Hermitage, S. A. Synlett 2004, 461. (b)
Karade, N. N.; Shirodkar, S. G.; Dhoot, B. M.; Waghmare, P. B. J. Chem.
Res. 2005, 274. Ammonium bromide: (c) Hashem, M. A.; Jung, A.; Ries,
M.; Kirschning, A. Synlett 1998, 195. (d) Brunjes, M.; Sourkouni-Argirusi,
G.; Kirschning, A. AdV. Synth. Catal. 2003, 345, 635. TMSBr: (e) Evans,
P. A.; Brandt, T. A. J. Org. Chem. 1997, 62, 5321.
3130
Org. Lett., Vol. 9, No. 16, 2007