Oxidation of alcohols to carbonyl compounds with diisopropyl azodicarboxylate catalyzed by nitroxyl radicals

Article abstract of DOI:10.1021/jo300088b

A nitroxyl-radical-catalyzed oxidation of alcohols using diisopropyl azodicarboxylate (DIAD) as the terminal oxidantis reported. A variety of primary and secondary alcohols including aliphatic, benzylic, and allylic alcohols are efficiently oxidized to their corresponding aldehydes and ketones without overoxidation to carboxylic acid. 1,2-Diols are oxidized to hydroxyl ketones or diketones depending on the amount of DIAD used.

Full text of DOI:10.1021/jo300088b

Note
pubs.acs.org/joc
Oxidation of Alcohols to Carbonyl Compounds with Diisopropyl
Azodicarboxylate Catalyzed by Nitroxyl Radicals
Masaki Hayashi,‡ Masatoshi Shibuya,† and Yoshiharu Iwabuchi*,†
†Department of Organic Chemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, 6-3 Aobayama, Sendai
980-8578, Japan
‡Process Technology Research Laboratories, Daiichi Sankyo Co., Ltd., 1-12-1 Shinomiya, Hiratsuka, Kanagawa 254-0014, Japan
S
* Supporting Information
ABSTRACT: A nitroxyl-radical-catalyzed oxidation of alcohols
using diisopropyl azodicarboxylate (DIAD) as the terminal oxidant
is reported. A variety of primary and secondary alcohols
including aliphatic, benzylic, and allylic alcohols are efficiently
oxidized to their corresponding aldehydes and ketones
without overoxidation to carboxylic acid. 1,2-Diols are oxidized
to hydroxyl ketones or diketones depending on the amount of
DIAD used.
he oxidation of alcohols to their corresponding carbonyl
compounds is one of the most fundamental trans-
formations in organic synthesis, and numerous methods have
been developed.1 In recent years, a stable class of nitroxyl
radicals, as exemplified by 2,2,6,6-tetramethyl piperidinyl 1-oxyl
[TEMPO (1); Figure 1], have been extensively used as a
We report herein an AZADO-catalyzed oxidation method using
diisopropyl azodicarboxylate (DIAD) as the terminal oxidant.
Dialkyl azodicarboxylates, as exemplified by DIAD and
diethyl azodicarboxylate (DEAD), are useful reagents in organic
synthesis, especially as a Mitsunobu reagent.5,6 They are also
versatile for promoting some particular transformations
including alcohol oxidation, azo-ene reaction, and hetero-
Diels−Alder reaction.7,8 Alcohol oxidation by DEAD was first
reported by Yoneda et al. in 1966 with a limited number of
examples.7d Recently, alcohol oxidation by a combination of
DEAD and a Lewis acid has been reported.8 Some primary and
secondary alcohols have been oxidized to their corresponding
carbonyl compounds by this method; unfortunately, the
method could not be applied to allylic or propargylic alcohols
because of unwanted side reactions. The oxidation of
hydroxylamines to nitroso compounds by DEAD under low
temperatures has also been reported.7b Inspired by this report,
we envisioned that dialkyl azodicarboxylate is a potential
oxidant for converting a nitroxyl radical into its corresponding
oxoammonium ion, which is a selective and efficient oxidant for
alcohols.
We first investigated the use of dialkyl azodicarboxylate as a
mild bulk oxidant for AZADO-catalyzed alcohol oxidation. The
initial experiment was carried out using ABNO as the catalyst
and DIAD as the bulk oxidant (Table 1).
We first treated 4-phenyl-2-butanol (5) with 1 mol % ABNO
and 1.2 equiv of DIAD in CH2Cl2 at room temperature; almost
no oxidation was observed even after 48 h (entry 1). We tested
some additives and found that the reaction proceeds in the
presence of acetic acid (entry 2).9 The result of the control
experiment carried out in the absence of ABNO indicated that
ABNO mediates this oxidation (entry 3). The reaction rate and
T
Figure 1. Structures of TEMPO and AZADOs.
catalyst for alcohol oxidation in a wide range of chemistry.2,3
Typically, TEMPO-based oxidations are carried out in the
presence of a catalytic amount of TEMPO and a stoichiometric
amount of bulk oxidants. Positive halogen source reagents such
as NaOCl3l are often used as bulk oxidants for TEMPO-based
oxidations. Although they are useful reagents from a practical
viewpoint, they often suffer from the undesirable halogenation
of electron-rich moieties such as double bonds and aromatic
rings. To prevent these side reactions, bis(acetoxy)iodobenzene
(BAIB) is often used as a mild bulk oxidant.3j
We have recently disclosed that 2-azaadamantane-, 9-
azanoradamantane-, and 9-azabicyclo[3.3.1]nonane-type nitroxyl
radicals (AZADOs; AZADO (2),4a,f Nor-AZADO (3),4c and
ABNO (4);4d Figure 1), which form a less-hindered class of
nitroxyl radicals, exhibit significantly enhanced reactivity
compared with TEMPO.4 They exhibit extremely high activities
toward a wide range of alcohols, including structurally hindered
secondary alcohols that cannot be efficiently oxidized by TEMPO.
With our continued interest in AZADOs-based oxidation, we have
searched for a mild terminal oxidant that allows for a chemo-
selective oxidation of alcohols with electron-rich functionalities.
Received: January 17, 2012
Published: February 21, 2012
© 2012 American Chemical Society
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Note
Table 1. Investigation of Reaction Conditions
Table 3. Scope of the Nor-AZADO/DIAD/AcOH System
ABNO
a
entry
(mol %) additive (equiv) CH2Cl2 (M) time (h) yield (%)
1
2
3
4
5
6
7
1
1
0.5
0.5
0.5
1.0
1.0
1.0
1.0
48
48
48
48
48
48
24
trace
80
1
AcOH (1)
AcOH (1)
AcOH (1)
AcOH (0.1)
AcOH (2)
AcOH(1)
1
1
1
3
88
25
86
88
a
The reactions were carried out with DIAD (1.2 equiv) at room
temperature.
yield were enhanced by increasing the concentration and the
catalyst loading amount (entries 4, 7).
We next compared the catalytic efficiencies of some nitroxyl
radicals in this system (Table 2). Nor-AZADO and AZADO
Table 2. Comparison of Catalytic Efficiency of Nitroxyl
a
Radicals
yield (%)
catalyst loading
(mol %)
ABNO
AZADO
Nor-AZADO
TEMPO
1(24 h)
1
3
88 (48 h)
88 (24 h)
81(24 h)
96 (24 h)
97 (24 h)
99 (24 h)
a
The reactions were carried out with DIAD (1.2 equiv) and AcOH
(1 equiv) in CH2Cl2 (1 M) at room temperature.
gave comparable results with a loading amount of 3 mol % and
showed superior catalytic efficiency compared to ABNO. Note
that TEMPO did not work as a catalyst in this system. The
difference between Nor-AZADO and AZADO became
apparent when the catalyst loading amount was decreased to
1 mol %; the reaction was completed within 24 h with 1 mol %
Nor-AZADO to give 6 in excellent yield, whereas the oxidation
using 1 mol % AZADO was not completed. We also tested azo-
compounds other than DIAD, such as diphenyl azodicarboxyl-
ate (DPAD), 1,1′-(azodicarbonyl) dipiperidine (ADD), azodi-
calboxamide, azobenzene, and 2,2′-azopyridene, and none of
them worked effectively.10
Having identified the optimum reaction conditions, we
explored the substrate applicability to the oxidation system
using Nor-AZADO as the catalyst (Table 3). A variety of
alcohols were efficiently oxidized to their corresponding
carbonyl compounds with 1−10 mol % catalyst. Aliphatic and
benzylic secondary alcohols, including a sugar derivative (9), an
N-protected amine (10), a nucleoside derivative (18), and a
pyridine derivative (20), were effectively oxidized (entries 1−7,
19, 22, 23). Relatively acid-labile isopropylidene and TBS-
protecting group remained after the reaction (entries 6, 19).
Primary alcohols were also oxidized to their corresponding
aldehydes in high yield without overoxidation to carboxylic
acids (entries 8−17, 24, 25). Note that 4-thiomethylbenzyl
a
The reactions were carried out with DIAD (1 equiv) and AcOH
b
(1 equiv) in CH2Cl2 (1 M) unless otherwise noted. 1.1 equiv of DIAD
was used. 2 equiv of DIAD was used. 2 equiv of AcOH was used.
c
d
alcohol (17) having a sulfide group was oxidized chemo-
selectively to its corresponding aldehyde (34) (entry 17).
We also tested some substrates containing amine functionalities.
In the case of 3-quinuclidinol (19), its corresponding ketone was
obtained in high yield, although 10 mol % catalyst was needed
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Note
(entry 21). However, the reaction failed to proceed in the cases of
other aminoalcohols such as 22 and 23 (entries 26, 27).
We then tested double- and triple-bond-containing substrates
and diols (Table 4). A variety of double-and triple-bond-
oxidation proceeded smoothly in the presence of acetic acid
with AZADOH to give 6 in high yield. These results indicate
that AZADO is not oxidized into an oxoammonium ion, which
is an active oxidant of typical nitroxyl-radical-catalyzed alcohol
oxidation, by DIAD in the absence of acetic acid. Thus, the
oxoammonium salt was thought to be generated by an acid-
catalyzed disproportionation of the nitroxyl radical.2f,12,13
We conducted the oxidation of 5 with stoichiometric amount
of AZADO and acetic acid in the absence of DIAD, wherein 6
was obtained in 40% yield, indicating that about half the
amount of the active oxoammonium salt was generated from
AZADO by acid disproportionation (Scheme 2).
Table 4. Scope of the Nor-AZADO/DIAD/AcOH System
Scheme 2. Oxidation with Nitroxyl Radical and Acetic Acid
On the basis of the above observations, we propose a
possible reaction pathway (Figure 2). Two molecules of
a
The reactions were carried out with DIAD (1 equiv) and AcOH
b
(1 equiv) in CH2Cl2 (1 M) unless otherwise noted. 1.2 equiv of DIAD
was used. 1.1 equiv of DIAD was used. 2 equiv of DIAD was used.
c
d
containing alcohols were oxidized in high yield at room
temperature (entries 1−6). Note that 1,2-diol was oxidized to a
hydroxyl ketone or a diketone depending on the amount of
DIAD used (entries 7−9).11 Primary alcohol was oxidized
selectively over secondary alcohol in the case of the diol 49,
which has both primary and secondary alcohols (entry 10).
To shed light on the reaction pathway, we conducted the
following experiments (Scheme 1). We first treated 5 with
Figure 2. Proposed reaction pathway for alcohol oxidation with
DIAD/AcOH/AZADOs.
AZADO were disproportionated to give AZADOH and an
oxoammonium salt with the aid of acetic acid. The
oxoammonium salt thus generated oxidizes an alcohol to give
its corresponding carbonyl compound and AZADOH.
AZADOH is then converted to AZADO by DIAD to establish
the catalytic cycle.
Scheme 1. Oxidation with Hydroxyl Amine
In conclusion, we have demonstrated that a combination of
AZADOs, DIAD, and acetic acid is an efficient system for
alcohol oxidation. The described procedure is simple, mild, and
applicable to a variety of alcohols including 1,2-diol. This mild
system would find good use in the alcohol oxidation of a variety
of substrates that cannot tolerate strong oxidants.
EXPERIMENTAL SECTION
■
General Experimental Procedures. The reagents were pur-
chased from commercial sources and used without further purification,
unless otherwise stated. Reactions were monitored by thin-layer
chromatography (TLC) carried out on 0.25 mm Merck silica gel plates
(60F-254). Column chromatograpy was performed using silica gel 60
(particle size, 0.063−0.210 mm). The eluents employed are reported
as volume:volume percentages.
AZADOH and DIAD in the absence of acetic acid; almost no
alcohol oxidation was observed after 48 h, but AZADOH was
oxidized to a nitroxyl radical, AZADO. In contrast, alcohol
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Note
Chemical shift (δ) is reported in parts per million (ppm) downfield
relative to tetramethylsilane (TMS) or CDCl3 (77.10 ppm). Coupling
constants (J) are reported in Hz. Multiplicities are reported using the
following abbreviations: s, singlet; d. doublet; t, triplet; q, quartet; m,
multiplet; br, broad.
2,4,5-Trimethylbenzaldehyde (32). 1H NMR (400 MHz,
CDCl3): δ 10.57 (s, 1H), 6.90 (s, 2H), 2.60 (s, 6H), 2.32 (s, 3H).
13C NMR (100 MHz, CDCl3): δ 192.9, 143.8, 141.4, 130.5, 130.0,
21.4, 20.5. IR (neat, cm−1): 1686. MS m/z: 148 (M+), 148 (100%).
HRMS (EI) calcd for C10H12O: 148.0888, found 148.0878.
1
Representative Procedure for Oxidation of Alcohols. A
solution of 4-phenyl-2-butanol (5) (97.7 mg, 0.651 mmol), Nor-
AZADO (90.0 μg, 0.00651 mmol), acetic acid (37.0 μL, 0.651 mmol),
and DIAD (0.128 mL, 0.651 mmol) in CH2Cl2 (0.65 mL) was refluxed
with stirring for 8 h. Saturated NaHCO3 (2 mL) was added and
extracted with CH2Cl2. The organic layer was dried over Na2SO4 and
concentrated under reduced pressure. The residue was purified by
silica gel column chromatography [hexane/Et2O (4:1 v/v)] to afford
2-phenyl-butan-2-one (6) (95.1 mg, 0.642 mmol, 99%) as a colorless oil.
p-Bromobenzaldehyde (33). H NMR (400 MHz, CDCl3): δ
9.98 (s, 1H), 7.75 (d, J = 8.7 Hz, 1H), 7.69 (d, J = 8.2 Hz, 1H). 13C
NMR (100 MHz, CDCl3): δ 191.0, 135.1, 132.4, 130.9, 129.8. IR
(neat, cm−1): 1688, 1066. MS m/z: 184 (M+), 185 (100%). HRMS
(EI) calcd for C7H5BrO: 183.9524, found 183.9523.
p-(Methylthio)benzaldehyde (34). 1H NMR (400 MHz,
CDCl3): δ 9.92 (s, 1H), 7.77 (d, J = 8.7 Hz, 2H), 7.33 (d, J = 8.2
Hz, 2H), 2.54 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 191.2, 147.9,
133.0, 130.0, 125.2, 14.7. IR (neat, cm−1): 1695. MS m/z: 152 (M+),
152 (100%). HRMS (EI) calcd for C8H8OS: 152.0296, found
152.0290.
1
4-Phenylbutan-2-one (6). H NMR (400 MHz, CDCl3): δ 7.28
(m, 2H), 7.22−7.16 (m, 3H), 2.89 (t, J = 7.5 Hz, 2H), 2.75 (m, 2H),
(t, J = 7.5 Hz, 2H), 2.14 (s, 3H). 13C NMR (100 MHz, CDCl3): δ
207.8, 140.9, 128.4, 128.2, 126.0, 45.1, 30.0, 29.6. IR (neat, cm−1):
1717. MS m/z: 148 (M+), 148 (100%). HRMS (EI) calcd for
C10H12O: 148.0888, found 148.0873.
9-(2′,5′-Bis-O-(tert-butyldimethylsilyl)-β-D-erythro-pentofuran-
1
3-ulosyl)-9H-adenine (35). H NMR (400 MHz, CDCl3): δ 8.36 (s,
1H), 8.14 (s, 1H), 6.13 (d, J = 8.2 Hz, 1H), 5.85 (br s, 2H), 4.94 (d,
J = 8.2 Hz, 1H), 4.29 (br s, 1H), 3.97 (m, 2H), 0.92 (s, 9H), 0.72 (s,
9H), 0.10 (s, 3H), 0.07 (s, 3H), −0.02 (s, 3H), −0.20 (s, 3H). 13C
NMR (100 MHz, CDCl3): δ 208.6, 155.5, 153.4, 150.4, 138.5, 119.8,
85.0, 82.4, 77.8, 62.4, 25.8, 25.3, 18.2, 18.0, −4.8, −5.5, −5.6, −5.7. IR
(neat, cm−1): 1788, 1647, 1595, 1577. MS m/z: 436 (M+ − tBu), 301
(100%). HRMS (EI) calcd for C22H39N5O4Si2: 493.2541, found
493.2511.
1
Menthone (24). H NMR (400 MHz, CDCl3): δ 2.35 (ddd, J =
12.8, 3.7, 2.3 Hz, 1H), 2.18−1.81 (m, 6H), 1.43−1.29 (m, 2H), 1.01
(d, J = 6.3 Hz, 3H), 0.91 (d, J = 6.8 Hz, 3H), 0.85 (d, J = 6.8 Hz, 3H).
13C NMR (100 MHz, CDCl3): δ 212.3, 55.8, 50.8, 35.4, 33.9, 27.8,
25.8, 22.2, 21.2, 18.6. IR (neat, cm−1): 1711. MS m/z: 154 (M+), 112
(100%). HRMS (EI) calcd for C10H18O: 154.1358, found 154.1343.
2,2-Dimethyl-1-phenylpropan-1-one (25). 1H NMR (400
MHz, CDCl3): δ 7.68 (d, J = 7.3 Hz, 2H), 7.48−7.38 (m, 3H), 1.35
(s, 9H). 13C NMR (100 MHz, CDCl3): δ 209.2, 138.6, 130.7, 128.0,
127.8, 44.1, 28.0. IR (neat, cm−1): 1676. MS m/z: 162 (M+), 105
(100%). HRMS (EI) calcd for C11H14O: 162.1045, found 162.1050.
1,2:4,5-Di-O-isopropylidene-β-D-erythro-2,3-hexadiulo-2,6-
1
3-Quinoclidinone (36). H NMR (400 MHz, CDCl3): δ 3.30 (s,
2H), 3.07−2.89 (m, 4H), 2.46 (quin, J = 3.0 Hz, 1H), 2.03−1.98 (m,
4H). 13C NMR (100 MHz, CDCl3): δ 219.6, 62.8, 46.9, 39.6, 25.6. IR
(neat, cm−1): 1725. MS m/z 125 (M+), 97 (100%). HRMS (EI) calcd
for C7H11NO: 125.0841, found 125.0834.
2-Acetylpyridine (37). 1H NMR (400 MHz, CDCl3): δ 8.69
(br d, J = 4.1 Hz, 1H), 8.05 (d, J = 8.0 Hz, 1H), 7.84 (td, J = 7.7,
1.7 Hz, 1H), 7.49−7.30 (m, 1H), 2.73 (s, 3H). 13C NMR (100 MHz,
CDCl3): δ 200.0, 153.6, 148.9, 136.8, 127.0, 121.6, 25.7. IR (neat,
cm−1): 1700; EI-MS m/z: 121 (M+), 79 (100%). HRMS (EI) calcd for
C7H7NO: 121.0528, found 121.0529.
1
pyranose (26). H NMR (400 MHz, CDCl3): δ 4.73 (d, J = 5.6 Hz,
1H), 4.61 (d, J = 9.4 Hz, 1H), 4.53(m, 1H), 4.39 (dd, J = 13.5, 2.2 Hz,
1H), 4.12 (d, J = 13.5 Hz, 1H), 4.00 (d, J = 9.4 Hz, 1H), 1.55 (s, 3H),
1.47 (s, 3H), 1.40 (s, 6H). 13C NMR (100 MHz, CDCl3): δ 196.9,
113.8, 110.6, 104.1, 77.9, 75.9, 70.0, 60.1, 27.1, 26.5, 26.0, 26.0. IR
(neat, cm−1): 1749. MS m/z: 259 (M+ + H), 114 (100%). HRMS (EI)
calcd for C12H19O6: 259.1182 (M+ + H), found 259.1164.
2-Thiophencarboxyaldehyde (38). 1H NMR (400 MHz,
CDCl3): δ 9.96 (d, J = 1.0 Hz, 1H), 7.80−7.77 (m, 2H), 7.22 (dd,
J = 4.8, 3.9 Hz, 1H), 2.54 (s, 3H). 13C NMR (100 MHz, CDCl3): δ
182.9, 144.1, 136.2, 135.1, 128.3. IR (neat, cm−1): 1672, 1419, 729.
MS m/z: 112 (M+), 112 (100%). HRMS (CI) calcd for C5H5OS:
113.0061 (M+ + H), found 113.0066.
1
trans-4-Carbobenzyloxiaminocyclohexanone (27). H NMR
(400 MHz, CDCl3): δ 7.37−7.31 (m, 5H), 5.12 (s, 2H), 4.75 (br s,
1H), 3.99 (br s, 1H), 2.45−2.40 (m, 4H), 2.28−2.24 (m, 2H), 1.75−
1.59 (m, 2H). 13C NMR (100 MHz, CDCl3): δ 209.5, 155.6, 136.3,
128.5, 128.2, 128.1, 66.8, 47.9, 38.8, 32.1. IR (neat, cm−1): 1704, 1530.
MS m/z: 247 (M+), 91 (100%). HRMS (EI) calcd for C14H17NO3:
247.1208, found 247.1206.
1
Cinnamylaldehyde (50). H NMR (400 MHz, CDCl3): δ 9.72
(d, J = 7.8 Hz, 1H), 7.59−7.56 (m, 2H), 7.49−7.42 (m, 4H), 6.74 (dd,
J = 15.9, 7.7 Hz, 2H). 13C NMR (100 MHz, CDCl3): δ 193.7, 152.7,
134.0, 131.2, 129.1, 128.6, 128.5. IR (CHCl3, cm−1): 1681. MS m/z:
132 (M+), 131 (100%). HRMS (EI) calcd for C9H8O: 132.0575,
found 132.0558.
4-Phenylbutanal (28). 1H NMR (400 MHz, CDCl3): δ 9.74
(d, J = 1.5 Hz, 1H), 7.30−7.15 (m, 5H), 2.65 (t, J = 7.7 Hz, 2H), 2.43
(dt, J = 7.2, 1.5 Hz, 2H), 1.95 (tt, J = 7.7, 7.2 Hz, 2H). 13C NMR (100
MHz, CDCl3): δ 202.2, 141.2, 128.4, 128.3, 126.0, 43.1, 34.9, 23.6. IR
(neat, cm−1): 1724. MS m/z: 148 (M+), 104 (100%). HRMS (EI)
calcd for C10H12O: 148.0888, found 148.0873.
1
2-Octenal (51). H NMR (400 MHz, CDCl3): δ 9.51 (d, J = 7.7
Hz, 1H), 6.85 (dt, J = 15.5, 6.8 Hz, 1H), 6.12 (ddt, J = 15.5, 7.7, 1.4
Hz, 1H), 2.36−2.31 (m, 2H), 1.55−1.28 (m, 2H), 1.37−1.30 (m, 4H),
0.92−0.89 (m, 3H). 13C NMR (100 MHz, CDCl3): δ 194.1, 158.9,
133.0, 32.7, 31.3, 27.5, 22.4, 13.9. IR (neat, cm−1): 1693, 1637. MS m/
z: 116 (M+), 70 (100%). HRMS (EI) calcd for C8H14O: 126.1045,
found 126.1050.
p-Nirobenzaldehyde (29). 1H NMR (400 MHz, CDCl3): δ 10.16
(s, 1H), 8.40 (dd, J = 8.8, 1.8 Hz, 2H), 8.08 (dd, J = 8.8, 1.8 Hz, 2H).
13C NMR (100 MHz, CDCl3): δ 192.3, 150.6, 140.1, 130.6, 124.2. IR
(neat, cm−1): 1709, 1537. MS m/z: 131 (M+), 151 (100%). HRMS
(EI) calcd for C7H5NO3: 151.0269, found 151.0253.
1
9-Decenal (52). H NMR (400 MHz, CDCl3): δ 9.77 (d, J = 1.9
Hz, 1H), 5.86−5.75 (m, 1H), 5.02−4.92 (m, 2H), 2.42 (dt, J = 7.2, 1.9
Hz, 2H), 2.04 (tt, J = 7.7, 7.2 Hz, 2H), 1.65−1.61 (m, 2H), 1.40−1.32
(m, 8H). 13C NMR (100 MHz, CDCl3): δ 202.8, 139.0, 114.2, 43.9,
33.7, 29.2, 29.1, 28.8, 28.8, 22.0. IR (neat, cm−1): 1727, 1640. MS m/z:
154 (M+), 68 (100%). HRMS (EI) calcd for C10H18O: 154.1358,
found 154.1369.
1
p-Methoxybenzaldehyde (30). H NMR (400 MHz, CDCl3): δ
9.89 (s, 1H), 7.84 (d, J = 8.7 Hz, 2H), 7.01 (d, J = 8.4 Hz, 2H), 3.89
(s, 3H). 13C NMR (100 MHz, CDCl3): δ 190.7, 164.6, 131.9, 129.9,
114.3, 55.5. IR (neat, cm−1): 1684. MS m/z: 136 (M+), 135 (100%).
HRMS (EI) calcd for C8H8O2: 136.0524, found 136.0526.
2,4-Dimethoxybenzaldehyde (31). 1H NMR (400 MHz,
CDCl3): δ 10.30 (s, 1H), 7.82 (d, J = 8.7 Hz, 1H), 6.55 (dd, J =
8.4, 2.9 Hz, 1H), 6.45 (d, J = 2.9 Hz, 1H), 3.91 (s, 3H), 3.88 (s, 3H).
13C NMR (100 MHz, CDCl3): δ 188.3, 166.2, 163.6, 130.7, 119.1,
105.7, 97.9, 55.6, 55.6. IR (neat, cm−1): 1670, 1266. MS m/z: 166
(M+), 166 (100%). HRMS (EI) calcd for C9H10O3: 166.0630, found
166.0625.
1
trans-3,7-Dimethyl-2,6-octadienal (53). H NMR (400 MHz,
CDCl3): δ 9.99 (d, J = 7.7 Hz, 1H), 5.88 (d, J = 8.2 Hz, 1H), 5.07
(m, 1H), 2.25−2.19 (m, 4H), 2.17 (s, 3H), 1.69 (s, 3H), 1.61 (s, 3H).
13C NMR (100 MHz, CDCl3): δ 191.2, 163.7, 132.9, 127.4, 122.5,
40.6, 25.7, 25.6, 17.7, 17.5. IR (neat, cm−1): 1675, 1632, 1611. MS
m/z: 152 (M+), 69 (100%). HRMS (EI) calcd for C10H16O: 152.1201,
found 152.1199.
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Note
1
3-Cyclohexene-1-carboxaldehyde (54). H NMR (400 MHz,
CDCl3): δ 9.70 (d, J = 0.97 Hz, 1H), 5.74−5.68 (m, 2H), 2.55−2.48
(m, 1H), 2.25−2.23 (m, 2H), 2.13−2.08 (m, 2H), 2.03−1.96 (m, 1H),
1.72−1.62 (m, 1H). 13C NMR (100 MHz, CDCl3): δ 204.4, 127.2,
124.7, 46.0, 24.3, 23.7, 22.1. IR (neat, cm−1): 1729, 1652. MS m/z: 110
(M+), 79 (100%). HRMS (EI) calcd for C7H10O: 110.0732, found
110.0725.
Y.; Liang, X. Chem.Eur. J. 2008, 14, 2679−2685. (d) Lei, M.; Hu,
R.-J.; Wang, R.-G. Tetrahedron 2006, 62, 8928−8932. (e) Liu, R.;
Liang, X.; Dong, C.; Hu, X. J. Am. Chem. Soc. 2004, 126, 4112−4113.
(f) Luca, L. D.; Giacomelli, G.; Masala, S.; Porcheddu, A. J. Org. Chem.
2003, 68, 4999−5001. (g) Miller, R. A.; Hoerrner, R. S. Org. Lett.
2003, 5, 285−287. (h) Luca, L. D.; Giacomelli, G.; Porcheddu., A. Org.
Lett. 2001, 3, 3041−3043. (i) Bolm, C.; Magnus, A. S.; Hildebrand,
J. P. Org. Lett. 2000, 2, 1173−1175. (j) De Mico, A.; Margarita, R.;
Parlanti, L.; Vescovi, A.; Piancatelli, G. J. Org. Chem. 1997, 62, 6974−
6977. (k) Einhorn, J.; Einhorn, C.; Ratajczak, F.; Pierre, J.-L. J. Org.
Chem. 1996, 61, 7452−7454. (l) Anelli, P. L.; Banfi, S.; Montanari, F.;
Quici, S. J. Org. Chem. 1989, 54, 2970−2972.
(4) AZADO is commercially available. Nor-AZADO and ABNO are
not commercially available but can be synthesized in several steps from
commercially available materials. (a) Shibuya, M.; Sasano, Y.;
Tomizawa, M.; Hamada, T.; Kozawa, M.; Nagahama, N.; Iwabuchi,
Y. Synthesis 2011, 3418−3425. (b) Shibuya, M.; Osada, Y.; Sasano, Y.;
Tomizawa, M.; Iwabuchi, Y. J. Am. Chem. Soc. 2011, 133, 6497−6500.
(c) Hayashi, M.; Sasano, Y.; Nagasawa, S.; Shibuya, M.; Iwabuchi, Y.
Chem. Phram. Bull. 2011, 59, 1570−1573. (d) Shibuya, M.; Tomizawa,
M.; Sasano, Y.; Iwabuchi, Y. J. Org. Chem. 2009, 74, 4619−4622.
(e) Shibuya, M.; Sato, T.; Tomizawa, M.; Iwabuchi, Y. Chem. Commun.
2009, 1739−1741. (f) Shibuya, M.; Tomizawa, M.; Suzuki, I.;
Iwabuchi, Y. J. Am. Chem. Soc. 2006, 128, 8412−8413.
1
Phenylpropynal (55). H NMR (400 MHz, CDCl3): δ 9.43 (s,
1H), 7.62−7.59 (m, 2H), 7.51−7.47 (m, 1H), 7.43−7.39 (m, 2H). 13C
NMR (100 MHz, CDCl3): δ 176.7, 133.3, 131.3, 128.7, 119.5, 95.1,
88.4. IR (neat, cm−1): 2188, 1660, 759. MS m/z: 130 (M+), 130
(100%). HRMS (EI) calcd for C9H6O: 130.0419, found 130.0405.
Benzoine (56). 1H NMR (400 MHz, CDCl3): δ 7.93−5.54
(m, 2H), 7.52−7.40 (m, 1H), 7.38−7.23 (m, 7H), 5.95 (d, J = 6.3 Hz,
1H), 4.55 (d, J = 6.3 Hz, 1H). 13C NMR (100 MHz, CDCl3): δ 198.9,
139.0, 133.8, 133.5, 129.1, 129.1, 128.6, 128.5, 127.7, 76.2. IR (neat,
cm−1): 3414, 1679. MS m/z: 212 (M+), 105 (100%). HRMS (EI)
calcd for C14H121O2: 212.0837, found 212.0829.
Benzil (57). H NMR (400 MHz, CDCl3): δ 7.99−7.96 (m, 4H),
7.68−7.63 (m, 2H), 7.53−7.49 (t, J = 7.7 Hz, 4H). 13C NMR (100
MHz, CDCl3): δ 194.5, 134.9, 133.0, 129.9, 129.0. IR (CHCl3, cm−1):
1660. MS m/z: 210 (M+), 105 (100%). HRMS (EI) calcd for
C14H10O2: 210.0681, found 210.0679.
1
5,6-Dodecandion (58). H NMR (400 MHz, CDCl3): δ 2.75−
2.71 (m, 4H), 1.60−1.53 (m, 4H), 1.37−1.29 (m, 8H), 0.93−0.86 (m,
6H). 13C NMR (100 MHz, CDCl3): δ 200.2, 200.2, 36.1, 35.8, 31.5,
28.8, 25.1, 23.0, 22.4, 22.3, 24.0, 13.8. IR (CHCl3, cm−1): 1711. MS m/
z: 199 (M+ + H), 199 (100%). HRMS (EI) calcd for C12H23O2:
199.1698 (M+ + H), found 199.1700.
(5) (a) Mitsunobu, O.; Yamada, M. Bull. Chem. Soc. Jpn. 1967, 40,
2380−2382. (b) Mitsunobu, O.; Yamada, M.; Mukaiyama, T. Bull.
Chem. Soc. Jpn. 1967, 40, 935−939.
(6) For a recent review on the Mitsunobu reaction, see: Swamy, K.
C. K.; Kumar, N. N. B.; Balaraman., E.; Kumar, K. V. P. P. Chem. Rev.
2009, 109, 2551−2651.
1
3-Hydroxy-2,2,4-trimethylpentanal (59). H NMR (400 MHz,
CDCl3): δ 9.62 (s, 1H), 3.55 (dd, J = 5.1, 4.1 Hz, 1H), 2.07 (br d, J =
5.4 Hz, 1H), 1.92−1.84 (m, 1H), 1.12 (d, J = 4.4 Hz, 6H), 0.97 (d, J =
6.8 Hz, 3H), 0.90 (d, J = 6.8 Hz, 3H). 13C NMR (100 MHz, CDCl3):
δ 206.7, 80.3, 50.5, 29.9, 21.7, 19.8, 18.6, 17.2. IR (neat, cm−1): 3479,
1714. MS m/z: 145 (M+ + H), 72 (100%). HRMS (EI) calcd for
C8H17O2: 145.1229 (M+ + H), found 145.1204.
(7) (a) Narasaka, K.; Morikawa, A.; Saigo, K.; Mukaiyama, T. Bull.
Chem. Soc. Jpn. 1977, 50, 2773−2776. (b) Taylor, E. C.; Yoneda, F.
Chem. Commun. 1967, 199−200. (c) Yoneda, F.; Suzuki, K.; Nitta, Y.
J. Org. Chem. 1967, 32, 727−729. (d) Yoneda, F.; Suzuki, K.; Nitta, Y.
J. Am. Chem. Soc. 1966, 88, 2328−2329.
́
(8) Cao, H. T.; Gree, R. Tetrahedron Lett. 2009, 50, 1493−1494.
(9) We also tested other stronger acids such as trifluoroacetic acid
and methansulfonic acid. They were found to be less effective,
resulting in lower yields.
ASSOCIATED CONTENT
* Supporting Information
■
S
(10) The reaction proceeded only when DPAD was used; however,
the yield was low (20%) because of unwanted side reactions.
(11) We tested the oxidation of 47 by Nor-AZADO (1 mol%) and
BAIB (1.5 equiv) in CH2Cl2 at room temperature. This reaction posed
an oxidative cleavage of 1,2-diol and afforded benzaldehyde in 60%
yield. For examples of oxidative cleavage of 1,2-diol by hypervalent
iodine, see: (a) Mu, R.; Liu, Z.; Yang, Z.; Liu, Z.; Wu, L.; Liu, Z.-L.
Adv. Synth. Catal. 2005, 347, 1333−1336. (b) Barton, D. H. R.;
Godfrey, C. R. A.; Morzycki, J. W.; Motherwell, W. B.; Stobie, A.
Tetrahedron Lett. 1982, 23, 957−960.
Copy of NMR spectra This material is available free of charge
via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: iwabuchi@mail.pharm.tohoku.ac.jp.
Notes
The authors declare no competing financial interest.
(12) (a) Golubev, V. A.; Zhdanov, R. I.; Gida, V. M.; E. Rozantsev, E.
G. Russ. Chem. Bull 1971, 20, 768−770. (b) Ma, Z.; Bobbitt, J. M
J. Org. Chem. 1991, 56, 6110−6114.
(13) We observed the generation of oxoammonium ion and hydroxyl
amine by acid-catalyzed disproportionation of AZADO by ESI-MS
measurement (see Supporting Information).
ACKNOWLEDGMENTS
■
This work was partly supported by a Grant-in-Aid for Scientific
Research (B) (No. 21390001) and by a Grant-in-Aid for Young
Scientists (A) (No. 23689001) from the Japan Society for the
Promotion of Science (JSPS).
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