Synthesis of imides, N-acyl vinylogous carbamates and ureas, and nitriles by oxidation of amides and amines with dess-martin periodinane

Article abstract of DOI:10.1002/anie.200501853

Expanding our synthetic tool repertoire: The DMP-mediated oxidation of a range of amide substrates has been demonstrated, affording the corresponding imides and N-acyl vinylogous carbamates and ureas. Likewise, an array of benzylic and related amines have also been successfully converted into their nitrile counterparts (see scheme; DMP = Dess-Martin periodinane). (Chemical Equation Presented)

Full text of DOI:10.1002/anie.200501853

Communications
successful employment for the construction of diverse arrays
of molecular targets.[1–3] As part of our explorations into the
realm of hypervalent iodine(v) chemistry, we recently
reported a number of useful applications involving both
Dess–Martin Periodinane (DMP) and o-iodoxybenzoic acid
(IBX). Included in these discoveries are the IBX-induced
conversion of amines into imines[4] and the initiation of
cascade reactions by DMP leading to a variety of imidoqui-
nones and heterocycles from anilide precursors.[5,6] The
intelligence gathered in the course of these investigations
led us to hypothesize about additional modes of reactivity that
could perhaps be unveiled through further explorations of the
chemistry of such hypervalent iodine(v) reagents toward
other classes of heteroatom-containing substrates. These
speculations proved fruitful, and herein we report the direct
oxidation of amides into imides and N-acyl vinylogous
carbamates and ureas, the dehydrogenation of benzylic and
related amines to aromatic nitriles by DMP, and applications
thereof.
Imides are well represented in the literature, often
appearing as productive components in a variety of reactions,
ranging from condensations to alkylations and from acyla-
tions to cycloadditions.[7] This structural motif also appears in
certain natural products such as fumaramidmycin,[8] conio-
thyriomycin,[9] and SB-253514.[10] Despite several procedures
being available for their preparation, new methods for the
synthesis of imides are nevertheless of considerable impor-
tance, especially when their direct access from readily
available substrates could be secured under mild conditions.
The mechanistic rationale for the oxidation of amides to
imides with DMP is shown in Scheme 1 A. Thus, it was
anticipated that nucleophilic attack onto the iodine core of
the reagent by the amide oxygen atom with concomitant
expulsion of an acetate group may lead to intermediate I,
whose spontaneous intramolecular rearrangement was antici-
pated to result in its collapse to Ac-IBA, AcOH, and N-acyl
imine intermediate 3. The latter, highly reactive, species 3
may then be transformed into imide 6, either by addition of
H2O, with subsequent oxidation of the putative hemiaminal
with DMP (Scheme 1 A, path A), or by the incorporation of
Ac-IBX (4), to generate an intermediate of type II (Sche-
me 1 A, path B).
This hypothesis proved correct as secondary amides were
smoothly oxidized to imides by heating with DMP in a
mixture of fluorobenzene and DMSO at 80–858C. As seen by
inspection of Table 1, an extensive range of functional groups
is tolerated by this protocol, including aromatic halides,
olefins, and acetates. Particularly significant are the results in
Table 1, entries 3and 5, which demonstrate the superiority of
the present method over contemporary techniques employing
RuO4,[11] a reagent whose tolerance of the olefinic and
ethereal sites of substrates 15 and 19, respectively, would be
questionable, at best.[12] Table 1, entries 7 and 8 are also
noteworthy as they provide information regarding chemo-
selectivity preferences for the action of DMP on amide-
containing substrates. Thus, carbamates are inert to these
oxidation conditions (Table 1, entry 7), as are benzylic
positions (Table 1, entry 8). The latter observation is expected
as DMP is not, unlike IBX,[13] a willing single-electron-
Oxidations
DOI: 10.1002/anie.200501853
Synthesis of Imides, N-Acyl Vinylogous
Carbamates and Ureas, and Nitriles by Oxidation
of Amides and Amines with Dess–Martin
Periodinane**
K. C. Nicolaou* and Casey J. N. Mathison
The synthetic utility and pervasiveness of hypervalent io-
dine(v) reagents have become increasingly evident in recent
decades, as underscored by a multitude of protocols that
highlight the oxidative capabilities of l5-iodanes and their
[*] Prof. Dr. K. C. Nicolaou, C. J. N. Mathison
Department of Chemistry
The Skaggs Institute for Chemical Biology
The Scripps Research Institute
10550 North Torrey Pines Road, La Jolla, California 92037 (USA)
and
Department of Chemistry and Biochemistry
University of California, San Diego
9500 Gilman Drive, La Jolla, California 92093 (USA)
Fax: (+1)858-784-2469
E-mail: kcn@scripps.edu
[**] We thank Dr. D. H. Huang and Dr. G. Siuzdak for NMR
spectroscopic and mass spectrometric assistance, respectively.
Financial support for this work was provided by grants from the
National Institutes of Health (USA) and the Skaggs Institute for
Chemical Biology.
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Table 1: Synthesis of imides by oxidation of amides with DMP.[a]
Entry
Substrate
Product
t
Yield
[h] [%][b]
1
11
13
12 1.0 98
2
14 0.5 86
3
4
15
17
16 3.0 61
18 0.5 98
5
6
7
8
9
19
21
23
25
27
20 5.0 96[c]
22 1.0 86
24 3.5 86[d]
26 2.0 98
28 1.0 92
Scheme 1. Mechanistic rationale for the DMP-mediated oxidation of
amides (A) and b-amido esters and amides (B). Ac-IBA=1-acetoxy-
1,2-benziodoxol-3(1H)-one; Ac-IBX=1-acetoxy-1-oxide-1,2-benziodoxol-
3(1H)-one.
transfer reagent. The minimal amount of DMSO is recom-
mended for this reaction as it was found that larger amounts
of this solvent (needed to ensure dissolution of certain
substrates) proved deleterious (see Table 1, entry 5).
[a] Reactions were conducted on a 0.2–0.5 mmol scale in PhF/DMSO
(minimal amount of DMSO) at 858C with DMP (2.0 equiv), unless
otherwise noted. [b] Yield of isolated product with no chromatography
necessary. [c] Based on 42% recovery of 19. [d] DMP: 6.0 equiv. DMSO=
dimethyl sulfoxide.
The relevance and potential utility of this novel route to
imides is underscored by a facile synthesis of the ethyl ester
analogue 31 of the antibiotic fumaramidmycin (32), as
depicted in Scheme 2. Thus, coupling of monoethyl fumarate
with amine 29 and subsequent oxidation of the resulting
amide (30) with DMP led to the targeted fumaramidmycin
analogue 31 (Table 4). This endeavor was instructive, as it not
only resulted in the specific synthesis of 31 in a most
expeditious manner but also hinted at the wealth of additional
natural or designed structures that could be easily accessed
through the developed technology.
Encouraged by these results, we further postulated that
secondary amides equipped with N-b-carbonyl structural
motifs could furnish vinylogous carbamates and ureas under
suitable conditions. This speculation, which rested on the
mechanistic rationale shown in Scheme 1B, proved well
founded as demonstrated in Table 2. Thus, the reaction
conditions have been demonstrated to favor the cis-config-
ured product, likely due to the stabilization provided by the
Scheme 2. Synthesis of the ethyl ester analogue of fumaramidmycin.
Reagents and conditions: a) monoethyl fumarate (0.5 equiv), EDC
(0.6 equiv), 4-DMAP (0.05 equiv), CH2Cl2, 258C, 19 h, 73%; b) DMP
(2.0 equiv), PhF/CH2Cl2/H2O (40:20:1), 858C, 14 h, 96% (36% conver-
sion). EDC=1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydro-
chloride; 4-DMAP=4-dimethylaminopyridine.
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Table 2: Synthesis of N-acyl vinylogous carbamates and ureas by oxidation of b-amido esters and amides with DMP.[a]
Entry
1
Substrate
Product
cis/trans
Yield [%][b]
98
33
35
37
39
34
36
38
40
>25:1
2
3
4
19:1
>25:1
23:1
55[b]
67
59[c]
5
6
7
41
43
45
42
44
46
>25:1
>25:1
6:1
52
29
73
[a] Reactions were conducted on 0.1–0.3 mmol scale in PhF at 858C for 1 h with DMP (5.0 equiv). [b] Based on 45% recovery of 35. [c] Based on 41%
recovery of 39. Bn=benzyl; Bz=benzoyl; THP=tetrahydropyranyl.
intramolecular hydrogen bond present within 9 and 10
(Scheme 1B) which is reinforced by the use of a nonpolar
solvent (fluorobenzene);[14] these conditions also tolerate the
presence of phenolic acetates (Table 2, entry 3) and N,N-
dibenzylamides (Table 2, entry 5). The latter example, in
particular, along with that in Table 2, entry 6, underscores the
oxidative potential of DMP, as it represents a direct dehy-
drogenation between two amide functionalities, a task very
few reagents, if any, can smoothly achieve. Possible applica-
tions of this type of synthetic transformation include the
construction of the N-acyl vinylogous urea and carbamic acid
structural domains found in palytoxin,[15] enamidonin,[16] and
CJ-15,801,[17] as specifically highlighted in Table 2, entry 7, in
which tetrahydropyranyl derivative 45 was oxidized with
DMP to compound 46, which could, in principle, be converted
into a palytoxin-like side chain following, among other steps,
cis–trans isomerization of the alkene.[14]
To highlight the applicability of this reaction further, a
formal total synthesis of the antibiotic CJ-15,801, along with
the construction of its cis isomer, was also completed from
commercially available starting materials (Scheme 3). Thus,
allylation of b-alanine (47),[18] followed by subsequent reac-
tion of the resulting amino ester 48 with d-(À)-pantolactone
in refluxing toluene, afforded diol 49. Acetonide formation
within 49 led to 50, whose oxidation with DMP gave a mixture
of the N-acyl vinylogous carbamates 51 (cis isomer) and 52
(trans isomer) in approximately 8:1 ratio in favor of the cis
compound. While the arrival at 52 (Table 4) signals a formal
total synthesis[19] of antibiotic CJ-15,801, the major isomer 51
was converted into cis-CJ-15,801 (53) by sequential cleavage
of the acetonide (BiCl3) and allyl ester ([Pd(PPh3)4])[20]
protecting groups (Scheme 3).
As a result of the aforementioned successes, we sought to
test the reactivity of DMP on additional nitrogen-containing
substrates, namely benzylic primary amines. We were
attracted by the prospect of directly accessing nitrile com-
pounds, intermediates and products whose ubiquitous appli-
cations in synthesis are well appreciated and documented.[21]
Our reasoning for this expectation is encapsulated in
Scheme 4. Thus, it was hypothesized that aromatic amine
substrates such as 55 could associate with DMP to form
complexes such as IV with concomitant loss of AcOH,
followed by an intramolecular benzylic hydrogen abstraction
by an acetate group. This would then result in a net
dehydrogenation to afford aldimines of type 56. These
fleeting intermediates would then be expected to be either
hydrolyzed by H2O to aldehydes (e.g. 57) or oxidized a second
time by DMP to furnish nitriles (e.g. 58).
Indeed, we were pleased to discover that an assortment of
benzylic and related primary amines undergo the projected
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Table 3: Dehydrogenation of amines to nitriles.[a]
Entry
Substrate
Product
t
Yield
[min] [%]
1
59
61
60 10
95
71
2
3
62 10
64 15
63
94
4
5
6
65
67
69
66 10
68 15
70 15
77
90[b]
77
7
71
72 15
84
Scheme 3. Formal total synthesis of the antibiotic CJ-15,801 (54) and
its cis isomer 53. Reagents and conditions: a) see reference [18]; b) d-
(À)-pantolactone (1.5 equiv), NaHCO3 (5.0 equiv), PhMe, reflux, 20 h,
59% (23% of 48 was also observed by 1H NMR prior to purification of
crude mixture); c) 2-methoxypropene (10 equiv), pTsOH (0.1 equiv),
acetone, 08C, 1 h, 78%; d) DMP (5.0 equiv), PhF, 858C, 2 h, 93%
(based on 39% recovered 50, cis and trans isomers isolated in ꢀ8:1
ratio, respectively); e) BiCl3 (0.2 equiv), H2O, MeCN, 258C, 14 h, 98%;
f) [Pd(PPh3)4] (0.2 equiv), dioxane/H2O (4:1), 258C, 14 h, 87%.
Ts =p-toluenesulfonyl.
[a] Reactions were conducted on a 0.2–0.5 mmol scale in CH2Cl2 at 258C
with DMP (2.0–3.0 equiv), unless otherwise noted. [b] DMP: 5.0 equiv.
bifunctional systems (entry 5). Aside from demonstrating
considerable tolerance, this DMP dehydrogenation protocol
has proven capable of affording nitriles through the imple-
mentation of brief reaction times, without excessive amounts
of aldehyde by-products, unlike previously reported proce-
dures employing iodosobenzene[22] or IBX.[4b]
The described chemistry expands the repertoire of
reactions carried out by DMP, a versatile oxidant with ever-
increasing utility in chemical synthesis. Among the reported
examples of new reactivity for this hypervalent iodine reagent
are the one-step oxidation of secondary amides to imides and
N-acyl vinylogous carbamates or ureas, and the direct
oxidation of benzylic and related primary amines to their
nitrile counterparts. The relevance of the present new
synthetic technology to a rapid synthesis of analogues of
fumaramidmycin and antibiotic CJ-15,801 demonstrates the
mildness and applicability of some of these protocols to
chemical synthesis, and bodes well for their future utilization
in other situations.
Scheme 4. Mechanistic rationale for the oxidation of benzylic and
related amines to aromatic nitriles with DMP.
Experimental Section
General procedure (amides): Generation of imides: In a sealed tube
the amide (0.1–0.3mmol) was dissolved in fluorobenzene (0.15 m) and
several drops of wet DMSO were added (or enough to ensure
dissolution of substrate). After addition of DMP (2.0 equiv), the
mixture was heated behind a blast shield at 80–858C until the starting
material was consumed (monitored by TLC analysis). The resulting
mixture was allowed to cool and was then quenched with saturated
transformation into nitriles upon reaction with DMP at 258C
in CH2Cl2. The generality and scope of this reaction is
demonstrated in Table 3with examples of substrates contain-
ing halide (Table 3, entries 3, 4, and 6), ether (entries 1 and 3),
electron-donating (entry 1), and electron-withdrawing
(entries 4 and 6) groups, as well as isoxazoles (entry 7) and
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5995

Communications
was quenched with saturated aqueous Na2S2O3 (2 mL) and the
resulting mixture was stirred vigorously until it became clear. The
mixture was then poured into Et2O (15 mL) and the ethereal phase
was washed twice with 10% aq. Na2S2O3/aq. NaHCO3 (1:1 mixture,
15 mL) and brine (15 mL) and then dried (MgSO4). Removal of the
solvent in vacuo afforded the nitrile, which was purified by silica-gel
column chromatography.
Table 4: Selected physical properties for 31, cis-34, 52, 53, and 64.
31: Rf =0.50 (silica gel, EtOAc/hexanes 1:2); IR (film): n˜max =3282, 2981,
1
1723, 1690, 1508, 1453, 1367, 1300, 1157, 1031 cmÀ1; H NM R
(400 MHz, CDCl3): d=8.04 (br s, 1H), 7.46 (d, J=15.2 Hz, 1H), 7.38–
7.32 (m, 3H), 7.28–7.26 (m, 2H), 6.90 (d, J=15.5 Hz, 1H), 4.27 (q,
J=7.0 Hz, 2H), 3.95 (s, 2H), 1.32 ppm (t, J=7.0 Hz, 3H); 13C NM R
(125 MHz, CDCl3): d=172.1, 165.0, 164.4, 134.8, 134.3, 133.0, 129.7,
129.1, 127.8, 61.7, 44.4, 14.2 ppm; HRMS (ESI TOF): calcd for
C14H15NO4Na+ [M+Na]+: 284.0893; found: 284.0898
Received: May 27, 2005
Published online: August 26, 2005
cis-34: Rf =0.78 (silica gel, EtOAc/hexanes 1:2); IR (film): n˜max =3311,
1
1673, 1616, 1480, 1395, 1378, 1220, 1030, 802, 695 cmÀ1; H NM R
Keywords: carbamates · hypervalent iodine · imides · nitriles ·
oxidation
.
(400 MHz, CDCl3): d=11.53 (br s, 1H), 7.97–7.95 (m, 2H), 7.74 (dd,
J=8.9, 11.2 Hz, 1H), 7.61–7.57 (m, 1H), 7.52–7.49 (m, 2H), 5.26 (d,
J=9.0 Hz, 1H), 4.24 (q, J=7.4 Hz, 2H), 1.33 ppm (t, J=7.4 Hz, 3H);
13C NMR (150 MHz, CDCl3): d=169.8, 164.7, 138.9, 133.1, 132.3, 129.1,
127.9, 97.4, 60.5, 14.4 ppm; HRMS (ESI TOF): calcd for C12H13NO3Na+
[M+Na]+: 242.0788; found: 242.0782
[1] D. B. Dess, J. C. Martin, J. Org. Chem. 1983, 48, 4155.
[2] D. B. Dess, J. C. Martin, J. Am. Chem. Soc. 1991, 113, 7277.
[3] V. V. Zhdankin, P. J. Stang, Chem. Rev. 2002, 102, 2523, and
references therein.
52: Rf =0.78 (silica gel, EtOAc/hexanes 1:1); [a]3D2 =+38 (CHCl3,
c=0.13); IR (film): n˜max =3331, 2947, 1715, 1635, 1495, 1378, 1298,
1256, 1195, 1134 cmÀ1; 1H NMR (500 MHz, CDCl3): d=8.41 (br d,
J=11.9 Hz, 1H), 8.00 (dd, J=13.8, 11.9 Hz, 1H), 5.98–5.90 (m, 1H),
5.62 (d, J=13.8 Hz, 1H), 5.33 (d, J=16.5 Hz, 1H), 5.23 (d, J=10.1 Hz,
1H), 4.65–4.64 (m, 2H), 4.20 (s, 1H), 3.71 (d, J=11.9 Hz, 1H), 3.32 (d,
J=11.9 Hz, 1H), 1.52 (s, 3H), 1.45 (s, 3H), 1.05 (s, 3H), 1.00 ppm (s,
3H); 13C NMR (125 MHz, CDCl3): d=168.1, 166.9, 136.5, 132.5, 118.1,
102.8, 99.7, 77.3, 71.4, 65.0, 33.6, 29.6, 22.0, 19.0, 18.8 ppm; HRMS
(ESI TOF): calcd for C15H23NO5Na+ [M+Na]+: 320.1468; found:
320.1464
[4] a) K. C. Nicolaou, C. J. N. Mathison, T. Montagnon, Angew.
Chem. 2003, 115, 4211; Angew. Chem. Int. Ed. 2003, 42, 4077;
b) K. C. Nicolaou, C. J. N. Mathison, T. Montagnon, J. Am.
Chem. Soc. 2004, 126, 5192.
[5] a) K. C. Nicolaou, P. S. Baran, R. Kranich, Y.-L. Zhong, K.
Sugita, N. Zou, Angew. Chem. 2001, 113, 208; Angew. Chem. Int.
Ed. 2001, 40, 202; b) K. C. Nicolaou, K. Sugita, P. S. Baran, Y.-L.
Zhong, Angew. Chem. 2001, 113, 213; Angew. Chem. Int. Ed.
2001, 40, 207; c) K. C. Nicolaou, Y.-L. Zhong, P. S. Baran, K.
Sugita, Angew. Chem. 2001, 113, 2203; Angew. Chem. Int. Ed.
2001, 40, 2145; d) K. C. Nicolaou, K. Sugita, P. S. Baran, Y.-L.
Zhong, J. Am. Chem. Soc. 2002, 124, 2221.
53: [a]3D2 =+18 (MeOH, c=0.08); IR (film): n˜max =3317, 2960, 2873,
[6] a) K. C. Nicolaou, Y.-L. Zhong, P. S. Baran, Angew. Chem. 2000,
112, 63 6;Angew. Chem. Int. Ed. 2000, 39, 622; b) K. C. Nicolaou,
P. S. Baran, Y.-L. Zhong, K. Sugita, J. Am. Chem. Soc. 2002, 124,
2212.
1
1655, 1625, 1467, 1402, 1320, 1243, 1108, 1044 cmÀ1; H NM R
(500 MHz, CD3OD): d=7.37 (d, J=8.4 Hz, 1H), 5.18 (br s, 1H), 4.03 (s,
1H), 3.48 (d, J=11.0 Hz, 1H), 3.39 (d, J=11.0 Hz, 1H), 0.93 (s, 3H),
0.92 ppm (s, 3H); 13C NMR (125 MHz, CD3OD): d=174.4 (2C), 133.8,
129.9, 77.0, 70.0, 40.7, 21.4, 20.6 ppm; HRMS (ESI TOF): calcd for
[7] Representative procedures highlighting the utility of imides in
synthesis include the reported construction of various 3-
hydroxypyrroles, 1,3,4-triazines, and multifarious enantioen-
riched b-substituted imides and esters: a) for 3-hydroxypyrroles,
see: W. Flitsch, K. Hampel, M. Hohenhorst, Tetrahedron Lett.
1987, 28, 4395; b) for 1,3,4-triazines, see, for example: N.
Jagerovic, L. Hernandez-Folgado, I. Alkorta, P. Goya, M.
Navarro, A. Serrano, F. Rodriguez de Fonseca, M. T. Dannert,
A. Alsasua, M. Suardiaz, D. Pascual, M. I. Martin, J. Med. Chem.
2004, 47, 2939; c) for b-substituted imides and esters, see: C. D.
Vanderwal, E. N. Jacobsen, J. Am. Chem. Soc. 2004, 126, 14724.
[8] a) H. B. Maruyama, Y. Suhara, J. Suzuki-Watanabe, Y. Mae-
shima, N. Shimizu, M. Ogura-Hamada, H. Fujimoto, K. Takano,
J. Antibiot. 1975, 28, 636; b) Y. Suhara, H. B. Maruyama, Y.
Kotoh, Y. Miyasaka, K. Yokose, H. Shirai, K. Takano, P. Quitt, P.
Lanz, J. Antibiot. 1975, 28, 648.
[9] K. Krohn, C. Franke, P. G. Jones, H.-J. Aust, S. Draeger, B.
Shultz, Liebigs Ann. Chem. 1992, 789.
[10] J. Thirkettle, E. Alvarez, H. Boyd, M. Brown, E. Diez, J. Hueso,
S. Elson, M. Fulston, C. Gershater, M. L. Morata, P. Perez, S.
Ready, J. M. Sanchez-Pulles, R. Sheridan, A. Stefanska, S. Warr,
J. Antibiot. 2000, 53, 664.
[11] a) For the first report of a RuO4-based oxidation of an acyclic
amide, see: L. M. Berkowitz, P. N. Rylander, J. Am. Chem. Soc.
1958, 80, 6682; b) for the scope of the reaction with RuO4, see:
K. Tanaka, S. Yoshifuji, Y. Nitta, Chem. Pharm. Bull. 1987, 35,
364.
[12] V. S. Martin, J. M. Palazon, C. M. Rodriguez in Encyclopedia of
Reagents for Organic Synthesis (Ed.: L. A. Paquette), Wiley,
West Sussex, 1995, p. 4415.
À
C9H14NO5 [MÀH]À: 216.0877, found: 216.0875
64: Rf =0.68 (silica gel, EtOAc/hexanes 1:2); IR (film): n˜max =3449, 1570,
1488, 1449, 1262, 1199, 929, 765 cmÀ1; 1H NMR (500 MHz, CDCl3):
d=7.43 (dd, J=8.5, 7.4 Hz, 2H), 7.36 (t, J=8.5 Hz, 1H), 7.27–7.24 (m,
1H), 7.17 (dd, J=8.1, 0.8 Hz, 1H), 7.11–7.09 (m, 2H), 6.73 ppm (dd,
J=8.8, 0.8 Hz, 1H); 13C NMR (125 MHz, CDCl3): d=161.5, 154.7,
138.3, 134.2, 130.4, 125.7, 123.5, 120.5, 114.6, 113.3 ppm; HRMS
(ESI TOF): calcd for C13H8ClNOH+ [M+H]+: 230.0367, found: 230.0359
aqueous Na2S2O3 (2 mL) and stirred vigorously until the solution
became clear. The mixture was poured into Et2O (15 mL) and the
ethereal phase was washed twice with 10% aq. Na2S2O3/aq. NaHCO3
(1:1 mixture, 15 mL) and brine (15 mL), and then dried (MgSO4).
Removal of the solvent in vacuo afforded the imide, often pure
1
enough (by NMR spectroscopic analysis) to forgo chromatography.
Generation of N-acyl vinylogous carbamates and ureas: In a sealed
tube the amide (0.1–0.3mmol) was dissolved in fluorobenzene (0.1 m)
and DMP (5.0 equiv) was added. The mixture was heated at 80–858C
until full consumption of starting material was noted (monitored by
TLC analysis). The reaction mixture was then quenched and purified
in the same manner as for the preparation of imides described above.
General procedure (amines): The amine (0.1–0.4 mmol) was
dissolved in a small amount of CH2Cl2 and added dropwise over a
period of 5–10 min to a homogeneous mixture of DMP (2.0 equiv) in
CH2Cl2 to form a 0.15m solution with respect to the amine. The
reaction mixture was stirred at 258C until the starting material was
consumed (as observed by TLC analysis), at which time the reaction
[13] a) For the role of IBX as a single-electron-transfer oxidant in
benzylic oxidations, see: K. C. Nicolaou, P. S. Baran, Y.-L.
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Chemie
Zhong, J. Am. Chem. Soc. 2001, 123, 3183; b) See also: K. C.
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