Intramolecular Büchner Reaction and Oxidative Aromatization with SeO₂ or O₂

Abstract

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.

Introduction

Intra- or intermolecular addition of diazo compounds with aromatic compounds gave cycloheptatrienes (CHTs) and norcaradienes by cyclopropanation and reversible electrocyclic ring opening (Büchner reaction).^1,2) Recently, CHTs have been utilized in organic synthesis as a source of carbene species by Au-catalyzed retro-Büchner reaction.^3–9) For broadening the synthetic utility of CHTs, we envisioned that the combination of Büchner reaction of 1 and aromatization of CHT 2 or an isomerized CHT 3 would provide a new methodology for synthesis of substituted arenes 4 (Chart 1). Besides retro-Büchner reaction, oxidative aromatization of CHTs has been reported to date.¹⁰⁾ For example, sensitized photooxidation of CHT with O₂^11,12) gave benzaldehyde in a trace amount.^13,14) Oxidation 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 benzaldehyde quantitatively.¹⁷⁾ In addition, a few examples of oxidation 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 photooxygenation 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

Chart 2. Reported Examples for Oxidative Aromatization of CHTs

Results and Discussion

Cycloheptatriene 2a was prepared by intramolecular Büchner 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 on 2a′ are shown in Table 1.

Table 1. Oxidation of 2a and 2a′

Entry	Substrate	Oxidation	8a (%)a)	9a (%)a)
1	2a (71)b)	CAN (4 equiv), MeCN, reflux, 2 h	0	0
2	2a′	CAN (4 equiv), MeCN, reflux, 5 h	0	0
3	2a (67)b)	PIFA (1.3 equiv), CH2Cl2, reflux, 18 h	0	0
4	2a′	PIFA (1.3 equiv), CH2Cl2, reflux, 18 h	4c)	4
5	2a (93)b)	SeO2 (3 equiv), CH2Cl2, r.t., 1 d	60 d)	trace
6	2a′	SeO2 (3 equiv), CH2Cl2, r.t., 1 d	NRe)	NRe)
7	2a (76)b)	O2, silica gel, CH2Cl2, r.t., 2 d	trace	39 f)
8	2a′	O2, silica gel, CH2Cl2, r.t., 2 d	NRe)	NRe)

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.

Oxidation of CHT 2a and a conjugated CHT 2a′ with CAN did not provide either 8a or 9a and gave a complex mixture (entries 1 and 2). Aromatic compounds 8a and 9a were not detected in a crude product by oxidation of 2a with PIFA¹⁷⁾ (entry 3), while oxidation of 2a′ with PIFA gave 8a (4%), 9a (4%), and 6-formyl-1-tetralone (18%) (entry 4).²⁰⁾

Treatment of a crude 2a with three equivalents of SeO₂²¹⁾ at room temperature (r.t.) for 1 d gave an aldehyde 8a in 60% yield along with a trace amount of 9a (entry 5). Oxidation of the crude 2a with 1.1 eq of SeO₂ at r.t. for 1.5 d gave 8a in a lower (32%) yield. When the same oxidation was carried out in refluxing CH₂Cl₂ by using 1.1 eq of SeO₂ for 1 d, 8a was obtained in 38% yield. Thus, three equivalents of SeO₂ were required for effective conversion of 2a to 8a. On the other hand, oxidation of the isomer 2a′ with SeO₂ did not proceed (entry 6). Oxidation of 2a with O₂ (1 atm) in the presence of silica gel in dichloromethane at r.t. for 2 d gave 1-tetralone (9a) in 39% yield along with a trace amount of aldehyde 8a (entry 7). In this case, photoirradiation was not conducted. In the absence of silica gel, conversion of 2a to 9a with O₂ did not proceed. Use of acetic acid (3 equiv) instead of silica gel also promoted oxidation of 2a with O₂ to 9a, but 9a was obtained less efficiently. In the absence of O₂, 9a was not formed by treatment with silica gel. Therefore, both silica gel and O₂ were necessary for conversion of 2a to 9a. We have screened other reaction conditions such as solvents, reaction temperatures, and reaction times, but it was difficult to improve the yield of 9a. Oxidation of the conjugated isomer 2a′ with O₂ in the presence of silica gel did not proceed (entry 8).

Regioselective formation of a formyl derivative 8 and a one-carbon-lacking 1-tetralone 9 prompted us to investigate more examples of oxidation of unconjugated CHTs 2 (Table 2). Oxidation of phenyl-substituted CHT 2b with SeO₂ gave aldehyde 8b in 48% yield along with 7-phenyl-1-tetralone (9b) and 6-phenyl-1-tetralone (9b′) in 7% combined yield (9b/9b′ = > 10 : 1) (entry 1). The structure of 9b and 9b′ was confirmed by ¹H-NMR analysis. Catalytic oxidation of 2b using SeO₂ (10 mol%) 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 6% yields, respectively (entry 2). Similarly, oxidation of methyl-, methoxy-, or acetoxy-substituted CHTs (2c–e) revealed that oxidation with SeO₂ gave aldehydes 8c–e mainly, while oxidation with O₂ and silica gel gave 7-substituted 1-tetralones 9c–e as the major isomers (entries 3–8). Oxidation of substituted 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 corresponding 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).

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	Ph	CH2	1b	68 (70)e)	SeO2	48 (22)e)	7 (12)e)	>10 : 1 (8 : 4)e)
2			1b	74	O2, silica gel	2	20	14 : 6
3	Me	CH2	1c	72	SeO2	38	trace	—
4			1c	78	O2, silica gel	3	25	19 : 6
5	MeO	CH2	1d	63	SeO2	<7f)	0	—
6			1d	77	O2, silica gel	trace	8	5 : 3
7	AcO	CH2	1e	58	SeO2	33	1	9e only
8			1e	56	O2, silica gel	<13	20	16 : 4
9	H	NCbz	1f	87	SeO2	36	4	—
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, 1 d. Reaction conditions of oxidation with O₂: O₂, silica gel, CH₂Cl₂, r.t., 2 d. 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., 2 d). 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.

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 regioselectively. Rational reasons for regioselective formation of 11 or 12 are not clear. The role of silica gel was not clarified, but we believe silica gel promoted the formation of 11 or 12. Isomerization to the corresponding norcaradiene 13 or 14 followed by C–H bond scission and cyclopropane ring cleavage affords aldehyde 8,²²⁾ while that followed by C–C bond scission and cyclopropane ring cleavage gives one-carbon-lacking 1-tetralones 9 and CO.^16,23)

Chart 3. A Proposed Mechanism

In conclusion, we have developed two reactions for oxidative aromatization of substituted CHTs. Oxidation of intramolecular Büchner adducts of 1-diazo-5-phenylpentan-2-ones with SeO₂ gave 8-formyl-1-tetralones regioselectively, while that with O₂ in the presence of silica gel gave one-carbon-lacking 1-tetralones. These new chemical reactivities of CHTs would contribute to further development of the synthetic application of CHTs.

Acknowledgments

This work was supported by Kanazawa University SAKIGAKE project.

Conflict of Interest

The authors declare no conflict of interest.

Supplementary Materials

The online version of this article contains supplementary materials.

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