there isnoreport describing the utilization of a hypervalent
iodine reagent acting as a coupling reagent in the conden-
sation of carboxylic acids with alcohols or amines. Herein,
in connection with our ongoing research programs on
chemistry of hypervalent iodine reagents,7 we report that a
hypervalent iodine(III) reagent iodosodilactone (1, Figure 1)
can function as an efficient coupling reagent to promote the
direct esterification including macrolactonization, direct
amidation, and peptide coupling without racemization. An
advantage with the use of 1 is that it can be easily regenerated
from the reaction mixture.
equiv of PPh3 in toluene under reflux for 1 h, which was
one of the optimal reaction conditions. Another experi-
ment showed that the reaction also proceeded very well in
chloroform (for details of the optimization, see Table S1,
Supporting Information). Two conventional hypervalent
iodine(III) reagents PIDA and phenyliodine ditrifluoroa-
cetate (PIFA) were also tested; however, the desired ester
5aa was only isolated in 27% and 17% yield, respectively.
The ready regeneration of 1 could be achieved after the
esterification between 3a (7 mmol) and 4a (5 mmol)
promoted by 1 (6 mmol). Upon quenching of the reaction
with saturated aq NaHCO3, the aqueous layer was col-
lected and acidfied, followed by direct oxidation with aq
NaOCl, and could yield 1 in 94% yield without the loss of
reactivity.7a
To investigate the scope of the reaction, a variety of
alcohols were examined under optimal reaction condi-
tions (Scheme 1). The desired esters can be obtained in
good to excellent yields regardless of primary alcohols
(5aaꢀae) or secondary alcohol (5af) with 3a. Sterically
hindered secondary alcohol L-menthol also performed
well and yielded the corresponding optically pure ester
product 5ag with retention of configuration around the
alkoxy carbon. Even the tertiary alcohol 2-methyl-1-
phenylpropan-2-ol could be converted to the corre-
sponding ester 5ah, although it is less reactive than
others. Moreover, the esterification of p- or m-nitrophe-
nol could take place and the corresponding ester pro-
ducts were produced in good yields (5ai and 5aj). Both
aliphatic and aromatic carboxylic acids were employed
and provided desired esters in good to excellent yields
with 4a (5baꢀfa). Multiple CꢀC bond could be well
tolerated under the present conditions (5ad and 5ae).
When N-Bz-proline was treated with 4a, N-benzoylpro-
linate 5ga was produced in 91% yield. Small amounts of
byproduct from the condensation of 2 with 4a were
observed in two examples (5da and 5ea). In a preliminary
experiment, we tested the macrolactonization of HO-
(CH2)11CO2H using 1 (2.0 equiv), DMAP (2.4 equiv),
and PPh3 (2.0 equiv) in toluene under reflux; however,
only a trace amount of 12-dodecanolide (5h) was
obtained (for details, see Table S2, Supporting
Information). Inspired by Keck macrolactonization,3f
the proton source compound pyridinium chloride was
added together with the use of pyridine instead of
DMAP, the desired product 5h was produced in 56%
yield. Under the optimal conditions, a series of hydroxy
acids, HO(CH2)nCO2H (n = 11, 14, 15) were utilized in
the macrolactonization. As indicated in Scheme 1, the
desired lactones (5hꢀj) were formed in good to excellent
yields, and a tendency was apparent that the longer
carbon chain in the hydroxy acids would result in the
better efficiency of macrolactonization. Notably, macro-
lactonization of (R)-(þ)-ricinoleic acid provided 5k
with complete retention of the configuration around the
alkoxy carbon, which has commercial importance in the
fragrance industry.
Figure 1. ORTEP drawing (the thermal ellipsoids drawn at the
50% probability level) of 1 and its synthetic precursor 2.
Compound 1 can be quantitatively prepared from the
commercially available 2-iodoisophthalic acid (2) by oxi-
dation with sodium hypochlorite (NaOCl) in aqueous
hydrochloric acid according to our reported procedure7a
instead of the literature protocol involving the use of
peracetic acid.8a The single crystal of 1 was first obtained
from DMSO, and its X-ray crystallographic analysis
showed a structure of overall planar shape unlike other
usually employed aryl-λ3-iodanes such as phenyliodine
diacetate (PIDA) with a typical T-shape structure. Com-
pound 1 is neither air nor moisture sensitive and can be
stored for several months at room temperature without
any detectable decomposition.
The study of the chemical reactivity of 1 was then carried
out. Compound 1 was found to be able to promote the
esterification between n-hexanoic acid (3a, 1.4 equiv) and
2-phenylethanol (4a, 1.0 mmol) in 91% yield together with
1.2 equiv of 4-dimethylaminopyridine (DMAP) and 1.0
(5) Dess, D. B.; Martin, J. C. J. Org. Chem. 1983, 48, 4155–4156.
(6) For selected reviews and books on hypervalent iodine reagents,
see: (a) Varvoglis, A. Hypervalent Iodine in Organic Synthesis; Academic
Press: London, 1997. (b) Zhdankin, V. V.; Stang, P. J. Chem. Rev. 2002, 102,
2523–2584. (c) Topics in Current Chemistry; Wirth, T., Ed.; Springer:
Berlin, 2003; p 224. (d) Wirth, T. Angew. Chem., Int. Ed. 2005, 44, 3656–
3665. (e) Zhdankin, V. V.; Stang, P. J. Chem. Rev. 2008, 108, 5299–5358.
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(f) Zhdankin, V. V. ARKIVOC 2009, 1, 1–62. (g) Brand, J. P.; Gonzalez,
D. F.; Nicolai, S.; Waser, J. Chem. Commun. 2011, 47, 102–115.
(h) Merritt, E. A.; Olofsson, B. Synthesis 2011, 517–538.
(7) (a) Zhao, X.-F.; Zhang, C. Synthesis 2007, 551–557. (b) Li, X.-Q.;
Zhao, X.-F.; Zhang, C. Synthesis 2008, 2589–2593. (c) Li, X.-Q.; Zhang,
C. Synthesis 2009, 1163–1169. (d) Yu, J.; Zhang, C. Synthesis 2009,
2324–2328. (e) Li, X.-Q.; Wang, W.-K.; Zhang, C. Adv. Synth. Catal.
2009, 351, 2342–2350. (f) Yu, J.; Tian, J.; Zhang, C. Adv. Synth. Catal.
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Adv. Synth. Catal. 2010, 352, 2588–2598. (h) Cui, L.-Q.; Liu, K.; Zhang, C.
Org. Biomol. Chem. 2011, 9, 2258–2265. (i) Cui, L.-Q.; Dong, Z.-L.; Liu, K.;
Zhang, C. Org. Lett. 2011, 13, 6488–6491. (j) Yu, J.; Cui, J.; Hou, X.-S.; Liu,
S.-S.; Gao, W.-C.; Jiang, S.; Tian, J.; Zhang, C. Tetrahedron: Asymmetry
2011, 22, 2039–2055. (k) Yu, J.; Liu, S.-S.; Cui, J.; Hou, X.-S.; Zhang, C.
Org. Lett. 2012, 14, 832–835.
To explore the mechanism, an experiment using 18O-
labeled 3-phenylpropanol (90% 18O incorporation) was
(8) (a) Agosta, W. C. Tetrahedron Lett. 1965, 6, 2681–2685.
(b) Banks, D. F. Chem. Rev. 1966, 66, 243–266.
Org. Lett., Vol. 14, No. 12, 2012
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