Intramolecular Büchner reaction and oxidative aromatization with SeO2 or O2

Article abstract of DOI:10.1248/cpb.c19-00243

Intramolecular Büchner reaction of 1-diazo-5-phenylpentan-2-ones followed by oxidation with SeO₂ or O₂ in the presence of silica gel regioselectively gave 8-formyl-1-tetralones or one-carbon-lacking 1-tetralones, respectively.

Full text of DOI:10.1248/cpb.c19-00243

Vol. 67, No. 7
Chem. Pharm. Bull. 67, 729–732 (2019)
729
Note
Intramolecular Büchner Reaction and Oxidative Aromatization with
SeO2 or O2
Shunya Morita, Tomoyuki Yoshimura, and Jun-ichi Matsuo*
Division of Pharmaceutical Sciences, Graduate School of Medical Sciences, Kanazawa University; Kakuma-machi,
Kanazawa, Ishikawa 920–1192, Japan.
Received March 15, 2019; accepted April 7, 2019
Intramolecular Büchner reaction of 1-diazo-5-phenylpentan-2-ones followed by oxidation with SeO2 or
O2 in the presence of silica gel regioselectively gave 8-formyl-1-tetralones or one-carbon-lacking 1-tetralones,
respectively.
Key words Büchner reaction; cycloheptatriene; oxidative aromatization; selenium dioxide; dioxygen
on 2a′ are shown in Table 1.
Oxidation of CHT 2a and a conjugated CHT 2a′ with CAN
Introduction
Intra- or intermolecular addition of diazo compounds with
aromatic compounds gave cycloheptatrienes (CHTs) and nor- did not provide either 8a or 9a and gave a complex mixture
caradienes by cyclopropanation and reversible electrocyclic (entries 1 and 2). Aromatic compounds 8a and 9a were not
ring opening (Büchner reaction).1,2) Recently, CHTs have been detected in a crude product by oxidation of 2a with PIFA17)
utilized in organic synthesis as a source of carbene species by (entry 3), while oxidation of 2a′ with PIFA gave 8a (4%), 9a
Au-catalyzed retro-Büchner reaction.3–9) For broadening the (4%), and 6-formyl-1-tetralone (18%) (entry 4).20)
21)
synthetic utility of CHTs, we envisioned that the combination
Treatment of a crude 2a with three equivalents of SeO2
of Büchner reaction of 1 and aromatization of CHT 2 or an at room temperature (r.t.) for 1d gave an aldehyde 8a in 60%
isomerized CHT 3 would provide a new methodology for syn- yield along with a trace amount of 9a (entry 5). Oxidation of
thesis of substituted arenes 4 (Chart 1). Besides retro-Büchner the crude 2a with 1.1eq of SeO2 at r.t. for 1.5d gave 8a in a
reaction, oxidative aromatization of CHTs has been reported lower (32%) yield. When the same oxidation was carried out
to date.10) For example, sensitized photooxidation of CHT in refluxing CH2Cl2 by using 1.1eq of SeO2 for 1d, 8a was
with O211,12) gave benzaldehyde in a trace amount.13,14) Oxida- obtained in 38% yield. Thus, three equivalents of SeO2 were
tion of excess CHT with chromium trioxide in acetic acid
gave benzaldehyde in 19.5% yield.15) Ceric ammonium nitrate
(CAN) oxidized CHT to afford benzaldehyde (80%), benzene
(18%), and carbon monoxide.16) Also, treatment of CHT with
phenyliodine(III) bis(trifluoroacetate) (PIFA) afforded benzal-
dehyde quantitatively.17) In addition, a few examples of oxida-
tion of substituted CHTs to aromatic compounds have been
reported. Yagihara and colleagues reported that o-substituted
benzaldehydes 5 were formed in up to 14% yields by photo-
oxygenation of 7-substituted CHTs18) (Chart 2a). Celik and
Balci reported that a reaction of substituted CHTs with singlet
oxygen gave an aromatic compound 7 in addition to a [4+2]
adduct 619) (Chart 2b). We report here oxidative aromatization
of intramolecular Büchner adducts, with selenium dioxide or
O2 in the presence of silica gel.
Chart 1. Synthesis of Substituted Arenes by Intramolecular Büchner
Reaction, Isomerization, and Aromatization
Results and Discussion
Cycloheptatriene 2a was prepared by intramolecular Büch-
ner reaction of 1-diazo-5-phenylpentan-2-one (1a) with a
catalytic amount of Rh2(OAc)4 in refluxing dichloromethane.
Since many products were formed during purification of 2a
with column chromatography on silica gel, a crude product
of 2a was oxidized by using various oxidizing agents (Table
1). Two-step yields of aromatic compounds based on 1a are
shown in Table 1 when oxidation of 2a was carried out. Enone
2a′ was isolated in 54% yield for two steps from 1a as a stable
compound by treatment of 2a with alumina. In the case of
oxidation of 2a′, one-step yields of aromatic compounds based
Chart 2. Reported Examples for Oxidative Aromatization of CHTs
*To whom correspondence should be addressed. e-mail: jimatsuo@p.kanazawa-u.ac.jp
© 2019 The Pharmaceutical Society of Japan

730
Chem. Pharm. Bull.
Vol. 67, No. 7 (2019)
Table 1. Oxidation of 2a and 2a′
Entry
Substrate
Oxidation
8a (%)a)
9a (%)a)
1
2
3
4
5
6
7
8
2a (71)b)
2a′
CAN (4 equiv), MeCN, reflux, 2h
CAN (4 equiv), MeCN, reflux, 5h
PIFA (1.3 equiv), CH2Cl2, reflux, 18h
PIFA (1.3 equiv), CH2Cl2, reflux, 18h
SeO2 (3 equiv), CH2Cl2, r.t., 1d
SeO2 (3 equiv), CH2Cl2, r.t., 1d
O2, silica gel, CH2Cl2, r.t., 2d
0
0
0
0
2a (67)b)
2a′
0
4c)
60d)
NRe)
trace
NRe)
0
4
2a (93)b)
2a′
trace
NRe)
39f )
NRe)
2a (76)b)
2a′
O2, silica gel, CH2Cl2, r.t., 2d
a) Isolated yields. b) Yield of 2a by determination with 1H-NMR using 1,3,5-trimethoxybenzene or 4,4′-di-t-butyldiphenyl as an internal standard. c) 6-Formyl-1-tetralone
was also obtained in 18% yield. d) 5-Formyl-1-tetralone (<7%) and 6-formyl-1-tetralone (1%) were also obtained. e) No reaction. f ) Yield for two steps from 1a.
Table 2. Oxidation of Büchner Products 2 with SeO2 or O2
Entry
R
X
1
2 (% yielda))
Oxidationb)
8 (% yieldc))
9+9′ (% yieldc))
9/9′
1
2
Ph
CH2
1b
1b
1c
1c
1d
1d
1e
1e
1f
68 (70)e)
74
SeO2
48 (22)e)
7 (12)e)
>10:1 (8:4)e)
O2, silica gel
SeO2
2
38
20
trace
25
0
14:6
3
Me
CH2
CH2
CH2
NCbz
72
—
4
78
O2, silica gel
SeO2
3
19:6
—
5
MeO
AcO
H
63
<7f)
trace
33
6
77
O2, silica gel
SeO2
8
5:3
7
58
1
9e only
16:4
—
8
56
O2, silica gel
SeO2
<13
36
20
4
9
87
10
1f
83
O2, silica gel
4
31
—
a) Determined by 1H-NMR using 1,3,5-trimethoxybenzene or 4,4′-di-t-butyldiphenyl as an internal standard. b) Reaction conditions of oxidation with SeO2: SeO2 (3 equiv),
CH2Cl2, 1d. Reaction conditions of oxidation with O2: O2, silica gel, CH2Cl2, r.t., 2d. c) Isolated yield for two steps from 1. d) Oxidation was carried out by using O2 in the
absence of silica gel (CH2Cl2, r.t., 2d). e) A catalytic oxidation using SeO2 (0.1 equiv) and TBHP (1.1 equiv) was performed instead of a stoichiometric oxidation with SeO2.
f ) Compound 10 was isolated in 40% yield.
required for effective conversion of 2a to 8a. On the other proceed. Use of acetic acid (3 equiv) instead of silica gel also
hand, oxidation of the isomer 2a′ with SeO2 did not proceed promoted oxidation of 2a with O2 to 9a, but 9a was obtained
(entry 6). Oxidation of 2a with O2 (1 atm) in the presence of less efficiently. In the absence of O2, 9a was not formed by
silica gel in dichloromethane at r.t. for 2d gave 1-tetralone (9a) treatment with silica gel. Therefore, both silica gel and O2
in 39% yield along with a trace amount of aldehyde 8a (entry were necessary for conversion of 2a to 9a. We have screened
7). In this case, photoirradiation was not conducted. In the other reaction conditions such as solvents, reaction tempera-
absence of silica gel, conversion of 2a to 9a with O2 did not tures, and reaction times, but it was difficult to improve the

Vol. 67, No. 7 (2019)
Chem. Pharm. Bull.
731
Chart 3. A Proposed Mechanism
yield of 9a. Oxidation of the conjugated isomer 2a′ with O2 in tive aromatization of substituted CHTs. Oxidation of intra-
the presence of silica gel did not proceed (entry 8). molecular Büchner adducts of 1-diazo-5-phenylpentan-2-ones
Regioselective formation of a formyl derivative 8 and a with SeO2 gave 8-formyl-1-tetralones regioselectively, while
one-carbon-lacking 1-tetralone 9 prompted us to investigate that with O2 in the presence of silica gel gave one-carbon-
more examples of oxidation of unconjugated CHTs 2 (Table lacking 1-tetralones. These new chemical reactivities of CHTs
2). Oxidation of phenyl-substituted CHT 2b with SeO2 gave would contribute to further development of the synthetic ap-
aldehyde 8b in 48% yield along with 7-phenyl-1-tetralone plication of CHTs.
(9b) and 6-phenyl-1-tetralone (9b′) in 7% combined yield
(9b/9b′=>10:1) (entry 1). The structure of 9b and 9b′ was
Acknowledgments This work was supported by Kanaza-
confirmed by 1H-NMR analysis. Catalytic oxidation of 2b wa University SAKIGAKE project.
using SeO2 (10mol%) and tert-butyl hydroperoxide (1.1 equiv)
gave 8b (22%), 9b (8%), and 9b′ (4%). Oxidation of 2b with
O2 in the presence of silica gel gave 9b and 9b′ in 14% and interest.
6% yields, respectively (entry 2). Similarly, oxidation of meth-
Conflict of Interest The authors declare no conflict of
yl-, methoxy-, or acetoxy-substituted CHTs (2c–e) revealed
Supplementary Materials The online version of this ar-
that oxidation with SeO2 gave aldehydes 8c–e mainly, while ticle contains supplementary materials.
oxidation with O2 and silica gel gave 7-substituted 1-tetralones
9c–e as the major isomers (entries 3–8). Oxidation of substi-
tuted CHTs 2b–e with O2 gave two regioisomers of 1-tetralone
derivatives, 9b–e and 9b–e′. In the oxidation of methoxy-
substituted CHT 2d with SeO2, the desired aldehyde 8d was
obtained in <7% yield and compound 10 was isolated in
40% yield (entry 5). Oxidation of 2d with O2 in the presence
of silica gel afforded 9d and 9d′ in 8% combined yield along
with many unidentified byproducts (entry 6). Interestingly,
the formation of 6-substituted 1-tetralones 9b–e′ suggested
that a substitution pattern between R- and –XCH2CH2– on the
phenyl ring of 1b–e changed by the one-carbon contraction.
Büchner reaction of N-benzyloxycarbonyl (Cbz)-N-(4-diazo-3-
oxobutyl)aniline (1f) proceeded smoothly to afford the cor-
responding CHT 2f in good yields. Oxidation of 2f with SeO2
gave a formyl ketone 8f in 36% yield, while oxidation of 2f
with O2 in the presence of silica gel gave a ketone 9f in 31%
yield (entries 9 and 10).
References and Notes
1) Reisman S. E., Nani R. R., Levin S., Synlett, 2011, 2437–2442
(2011).
2) McNamara O. A., Buckley N. R., O’Leary P., Harrington F., Kelly
N., O’Keeffe S., Stack A., O’Neill S., Lawrence S. E., Slattery C.
N., Maguire A. R., Tetrahedron, 70, 6870–6878 (2014).
3) Solorio-Alvarado C. R., Wang Y.-H., Echavarren A. M., J. Am.
Chem. Soc., 133, 11952–11955 (2011).
4) Wang Y., McGonigal P. R., Herle B., Besora M., Echavarren A. M.,
J. Am. Chem. Soc., 136, 801–809 (2014).
5) Herlé B., Holstein P. M., Echavarren A. M., ACS Catal, 7, 3668–
3675 (2017).
6) Yin X., Mato M., Echavarren A. M., Angew. Chem. Int. Ed., 56,
14591–14595 (2017).
7) Mato M., Herle B., Echavarren A. M., Org. Lett., 20, 4341–4345
(2018).
8) Mato M., García-Morales C., Eschavarren A. M., ChemCatChem,
11, 53–72 (2019).
9) Saito K., Kozaki M., Takahashi K., Chem. Pharm. Bull., 41, 2187–
2189 (1993).
A proposed mechanism for oxidation of 2 to 8 or 9 is shown
in Chart 3. Treatment of 2 with SeO2 or O2 in the presence of
silica gel gives peroxide or selenium(II) ester 11 or 12 regi-
oselectively. Rational reasons for regioselective formation of
10) Sudrik S. G., Nanjundiah B. S., Sonawane H. R., Indian J. Chem.
Sect. B, 36B, 1103–1112 (1997).
11) Kende A. S., Chu J. Y. C., Tetrahedron Lett., 11, 4837–4840 (1970).
11 or 12 are not clear. The role of silica gel was not clarified, 12) Adam W., Balci M., J. Am. Chem. Soc., 101, 7537–7541 (1979).
13) Mori A., Takeshita H., Chem. Lett., 7, 395–396 (1978).
14) Asao T., Yagihara M., Kitahara Y., Bull. Chem. Soc. Jpn., 51,
2131–2135 (1978).
15) Mueller P., Rocek J., J. Am. Chem. Soc., 96, 2836–2840 (1974).
16) Trahanovsky W. S., Young L. B., Robbins M. D., J. Am. Chem. Soc.,
91, 7084–7089 (1969).
17) Çelik M., Alp C., Coşkun B., Güeltekin M. S., Balci M., Tetrahe-
but we believe silica gel promoted the formation of 11 or 12.
Isomerization to the corresponding norcaradiene 13 or 14 fol-
lowed by C–H bond scission and cyclopropane ring cleavage
affords aldehyde 8,22) while that followed by C–C bond scis-
sion and cyclopropane ring cleavage gives one-carbon-lacking
1-tetralones 9 and CO.16,23)
In conclusion, we have developed two reactions for oxida-

732
Chem. Pharm. Bull.
23) Formation of isomer 11′ or 12′ would lead 9′.
Vol. 67, No. 7 (2019)
dron Lett., 47, 3659–3663 (2006).
18) Asao T., Yagihara M., Kitahara Y., Heterocycles, 15, 985–991
(1981).
19) Celik M., Balci M., ARKIVOC, 2007, 150–162 (2007).
20) Treatment of 2a and 2a′ with AuSbF6-IMes (1,3-dimesitylimidazol-
2-ylidene) (5mol%) and stilbene (1.0 equiv) in refluxing DCE for 4h
did not afford 9a.
21) Radlick P., J. Org. Chem., 29, 960 (1964).
22) Doering W. E., Knox L. H., J. Am. Chem. Soc., 79, 352–356 (1957).