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Synlett 2012; 23(6): 867-872
DOI: 10.1055/s-0031-1290304
letter
© Georg Thieme Verlag Stuttgart · New York

Synthesis of 1-Indanonyl Oxepanes

Meng-Yang Chang*
Department of Medicinal and Applied Chemistry, Kaohsiung Medical University, Kaohsiung 807, Taiwan, R.O.C., Fax: +886(7)3125339   Email: mychang@kmu.edu.tw
,
Nien-Chia Lee
Department of Medicinal and Applied Chemistry, Kaohsiung Medical University, Kaohsiung 807, Taiwan, R.O.C., Fax: +886(7)3125339   Email: mychang@kmu.edu.tw
› Author Affiliations
Further Information

Publication History

Received: 20 December 2011

Accepted after revision: 25 January 2012

Publication Date:
28 February 2012 (online)

 
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Abstract

A variety of 1-indanonyl oxepanes with the novel structure of indanonyl oxepanes was prepared from reaction of hydroxybenzaldehydes via a series of reasonable transformations, including the regioselective PhBCl2-mediated allylation (or Claisen rearrangement), one-pot reaction of ring-closing metathesis and the Wittig olefination, hydrogenation, and the Friedel–Crafts intramolecular cyclization.


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Key words

heterocycles - metalation - metathesis - Wittig reaction - fused ring systems

The bicyclic benzofused ring system, along with related structures, such as benzo[b]oxepane, represents the structural motifs of benzooxacycloheptanes (Figure [1]). Recent reports on new methods for the preparation of benzo[b]oxepane have reflected the strong interest, in the synthesis of these useful building blocks.[1] [2] The cyclic system incorporates two rings connected by a fused ring containing a benzene ring adjacent to the ring junction. This structural motif has been observed in a number of natural alkaloid products such as radulanin A,[ 3 ] heliannuol A, B, C, and D,[ 4 ] and pterulone.[ 5 ] The structural framework of 1-indanone presents a particular challenge, and its formation is the main focus of the research presented in this area.[ 6 ] A number of unique approaches in regard to 1-indanone have been explored because of its important potential biological properties.[ 7 ] However, there is no example for synthesizing skeleton 1 with a combination of benzo[b]oxepane and 1-indanone.

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Figure 1 Structures of oxepane, 1-indanone, and skeleton 1

In this article, we report a simple route for synthesizing the novel skeleton 1 as shown in Scheme [1], which consists of a PhBCl2-mediated double allylation of 4-substituted 3-hydroxybenzaldehyde 4 with LDA, an one-pot combination of the ring-closing metathesis of diallyl compound 3 followed by the Wittig olefination of the resulting benzo[b]oxepane skeleton, the hydrogenation of ester 2, and basic hydrolysis of the resulting hydrogenated ester followed by polyphosphoric acid (PPA)-mediated Friedel–Crafts intramolecular acylation.

Zoom Image
Scheme 1 Retrosynthetic route of skeleton 1

Chattopadhyay[ 8 ] and Wang[ 9 ] reported that a general synthesis of benzofused oxepane via a sequential Claisen rearrangement and ring-closing metathesis was the key route. Herein, a more convenient route for synthesizing skeleton 1 was the PhBCl2-mediated double allylation of 4-substituted 3-hydroxybenzaldehyde 4 with LDA, as shown in Scheme [2].

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Scheme 2 Synthesis of 6-oxacyclohepta[e]indan-3-ones 1a–c

To initiate our work, the directed ortho metalation of model substrate 4a was studied.[ 10 ] The regioselective PhBCl2-mediated double allylation of compound 4a with a three equivalents of LDA provided a diallyl compound 3a in 62% yield via the possible boron complex chelated intermediate A (see Equation [1].).[ 10e ] The LDA should initiate the generated intermediate A so that the ortho C2-metalation can proceed. The C2 allylation was regioselectively formed from intermediate A, and then intermediate B was further transformed to compound 3a via the O-allylation of C3. Compounds 3b and 3c were also provided in 70% and 72% yields, respectively, under the above-mentioned metalation conditions. For preparing 3-allyl­oxy-2-allylbenzaldehyde 3, a convenient and efficient one-pot, double-allylation method was developed from 4-substituted 3-hydroxybenzaldehyde 4 with a moderate yield.

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Equation [ 1 ] Possible PhBCl2-mediated intermediate

In order to construct the benzo[b]oxepane skeleton, compound 3a with the diallyl group was first subjected to an intramolecular ring-closing metathesis by using the Grubbs second-generation catalyst in dichloromethane according to the reported conditions.[ 11 ] Next, the Wittig olefination of the resulting benzaldehyde bearing a seven-membered ring with Ph3P=CHCO2Et in dichloromethane afforded the α,β-unsaturated ester 2a. Because dichloromethane could be used as the same reaction solvent for ring-closing metathesis and Wittig olefination, a combination of the two steps was required. Comparing the two routes, we found that the one-pot reaction provided a higher yield (88%) than the two-step reaction process (75%). From the literature reports on the synthesis of a benzo[b]oxepane skeleton using the Claisen rearrangement as the key step, it was evident that the present methodology shortened the synthesis steps and increased the reaction yields. Compounds 2b and 2c were obtained in 80% and 85% yield, respectively, under the one-pot reaction conditions. Then, when skeleton 2 was treated with hydrogen in the presence of a catalytic amount of 10% palladium on activated carbon in EtOAc, compounds 5a–c were isolated in 93–98% yields. Finally, three 1-indanonyl oxepanes 1a–c, with a tricyclic skeleton, were obtained as sole isomers in yields of 65–77% via the NaOH-promoted hydrolysis of compounds 5a–c followed by the PPA-mediated Friedel–Crafts intramolecular ring closure of the resulting acids.[ 12 ] The structures of compounds 1a and 1c were determined using single-crystal X-ray analysis (Figure [2]).[13] [14]

Zoom Image
Figure 2 X-ray structure of compound 1c

With the successful results in hand, we attempted to prepare other tricyclic skeletons of 1-indanonyl oxepanes.[ 15 ] Six possible skeletons are shown in Figure [3]. Based on the relative position between the carbonyl group of the indanone skeleton and the oxygen atom of the oxepane skeleton, the structure of 1-indanonyl oxepane could be classified into three types: (i) one ortho-substituted skeleton A1, (ii) two para-substituted skeletons B1,2, and (iii) three meta-substituted skeletons C1–3. According to the above-mentioned analyses, we envisioned that the analogues 1 would be generated from hydroxybenzaldehydes 4a–c via the key Claisen rearrangement.[ 16 ]

Zoom Image
Figure 3 Six skeletons of 1-indanonyl oxepanes

As shown in Scheme [3], the unseparated mixture of compounds 3a and 3d was provided in 52% yields of three steps via the reaction sequence of O-allylation, Claisen rearrangement, and O-allylation. From the phenomenon, we found that the present route could not provide a regioselective Claisen rearrangement.[ 17 ] Treatment of the unseparated mixture with the one-pot reaction gave compounds 2a and 2d in 15% and 73% yields, respectively. Furthermore, compound 1d (skeleton B2) was easily yielded by the hydrogenation of compound 2d and ring closure of compound 5d. During the regioselective PPA-mediated Friedel–Crafts acylation, compound 1d was isolated as the sole product. Attempts to isolate skeleton A1 failed during the intramolecular cyclization. When the regioselective ring-closure step of acid substrate was treated with SOCl2 and AlCl3, compound 1e was achieved with a 49% yield without the formation of compound 1d.

Zoom Image
Scheme 3 Synthesis of 5-oxacyclohepta[f]indan-1-ones 1d–e
Zoom Image
Scheme 4 Synthesis of 5-oxacyclohepta[f]indan-3-one 1f and 6-oxacyclohepta[e]indan-1-one 1g

After the starting material was changed as 4-hydroxybenzaldehyde (4d), attempts to synthesize skeleton C2 or C3 were further studied (Scheme [4]). First, compound 3e provided a 69% yield by the three-step protocol. Next, treatment of compound 3e with the one-pot reaction of the ring-closing metathesis and the Wittig olefination afforded compound 2e in an 80% yield. After the hydrogenation of compound 2e and the Friedel–Crafts ring closure of compound 5e, compounds 1f (skeleton C3) and 1g (skeleton C2) were isolated in 60% and 19% yields, respectively. The preference for a linear formation was ascribed to the steric effect. The structures of linear compound 1f and angular compound 1g were constructed using single-crystal X-ray analysis.[ 13 ]

Furthermore, 2-hydroxybenzaldehyde (4e) was chosen as the reasonable starting material for constructing compound 1h (skeleton C1). The sole compound 1h was formed via the above-mentioned synthesis sequence (Scheme [5]): (i) three-step double allylation of compound 4e (40%); (ii) one-pot combination of compound 3f in a one-pot reaction with ring-closing metathesis and the ­Wittig olefination reaction (72%); (iii) hydrogenation of compound 5f (96%); and (iv) intramolecular ring closure of compound 5f (74%, two steps). Based on the above results, although the isolation of skeleton A1 could not been achieved, a variety of novel skeletons 1 with the structure of indanonyl oxepane was prepared from the reaction of hydroxybenzaldehydes.

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Scheme 5 Synthesis of 10-oxacyclohepta[e]indan-3-one 1h

With the previous experience of the one-pot combination reaction of compound 3c, including the ring-closing metathesis and the Wittig olefination reaction, two one-pot combinations with ring-closing metathesis were explored, as shown in Scheme [6]. The reaction of compound 3c was first treated with Grubbs second-generation catalyst in the presence of a catalytic amount of 10% palladium on activated carbon in dichloromethane, and hydrogen was then added into the mixture. By this addition sequence, compound 6 was isolated in a 70% yield via the one-pot combination reaction of ring-closing metathesis and hydrogenation. Then, compound 7 was synthesized in a 58% yield via (i) the ring-closing metathesis of compound 3c with Grubbs second-generation catalyst in dichloromethane, and then (ii) the Baeyer–Villiger reaction of the resulting aldehyde with K2CO3 and MCPBA. Using the same reaction solvent, the two one-pot combinations enhanced the synthesis efficiency and shortened the required purification time. The structural framework of compound 7 was constructed using single-crystal X-ray analysis.[ 13 ] Therefore, a domino reaction for establishing the benzo[b]oxepane skeletons 6 and 7 was provided.[ 18 ]

Zoom Image
Scheme 6 One-pot combination reaction of compound 3c

We have successfully presented the ortho-metalative-­mediated double allylation reaction of 4-substituted 3-hydroxybenzaldehydes 4a–c with PhBCl2 for producing three 4-substituted 1-indanonyl oxepanes 1a–c (skeleton B1). The Claisen rearrangement and one-pot combination reaction of compound 3a with the ring-closing metathesis and the Wittig olefination were applied to synthesize different 1-indanonyl oxepanes 1d–h, including several skeletons para-B2, meta-C1, meta-C2, and meta-C3. Several structures of the products were confirmed by X-ray crystal analysis.


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Acknowledgment

The authors would like to thank the National Science Council of the Republic of China for its financial support (NSC 99-2113-M-037-006-MY3).

  • References and Notes

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    • 12a Heaney H In Comprehensive Organic Synthesis. Vol. 2. Trost BM, Fleming I. Pergamon Press; Oxford: 1991: 733
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  • 13 CCDC 846976 (1a), 845967 (1c), 853005 (1f), 853004 (1g), and 845966 (7) contain the supplementary crystallographic data for this paper. This data can be obtained free of charge via www.ccdc.cam.ac.uk/conts/retrieving.html [or from the CCDC, 12 Union Road, Cambridge CB2 1EZ, UK; fax: +44(1223)336033; e-mail: deposit@ccdc.cam.ac.uk ]
  • 14 Representative Synthetic Transformation of Skeleton 1 from 5 A solution of 5 (0.4 mmol) and aq NaOH (6 M, 5 mL) in THF (10 mL) was refluxed for 6 h. The reaction was traced by TLC until 5 was completely consumed. The reaction solution was cooled to r.t. and concentrated until one third of the solution remained. The remained solution was extracted with EtOAc (3 × 10 mL). The aqueous phase was cooled in an ice-bath and acidified by adding concentrated aq HCl to pH 2. The aqueous solution was extracted with EtOAc (3 × 20 mL), and the extracts were washed with brine. The combined organic layers were washed with brine, dried, filtered, and evaporated to afford a crude acid product under reduced pressure. Without purification, PPA (3 mL) was added to a solution of the crude acid product in CH2Cl2 (5 mL) at r.t. The reaction mixture was stirred at r.t. for 4 h. Saturated aq NaHCO3 (10 mL) was added to the reaction mixture, and the residue was extracted with CH2Cl2 (3 × 30 mL). The combined organic layers were washed with brine, dried, filtered, and evaporated to afford the crude product under reduced pressure. Purification on silica gel (hexanes–EtOAc = 3:1) afforded skeleton 1. Representative Data for Compound 1a Colorless solid; mp 135–136 °C (recrystallized from hexanes and EtOAc). ESI-HRMS: m/z ] calcd for C13H15O2 203.1072 [M+ + 1; found: 203.1073. 1H NMR (400 MHz, CDCl3): δ = 7.54 (d, J = 8.0 Hz, 1 H), 6.98 (d, J = 8.0 Hz, 1 H), 4.10 (dd, J = 5.2, 5.6 Hz, 2 H), 3.02 (t, J = 5.6 Hz, 2 H), 2.85–2.82 (m, 2 H), 2.69–2.66 (m, 2 H), 2.05–1.99 (m, 2 H), 1.82–1.76 (m, 2 H). 13C NMR (100 MHz, CDCl3): δ = 205.94, 166.03, 155.93, 132.40, 131.52, 122.75, 121.61, 77.31, 73.29, 36.48, 31.60, 27.83, 24.88. Anal. Calcd for C13H14O2: C, 77.20; H, 6.98. Found: C, 77.51; H, 7.34. Single-crystal X-ray diagram shows that the crystal of compound 1a was grown by slow diffusion of EtOAc into a solution of compound 1a in CH2Cl2 to yield colorless prism. The compound crystallizes in the triclinic crystal system, space group P-1, a = 8.4928(2) Å, b = 10.5935(2) Å, c = 12.4192(2) Å, V = 1032.67(4) Å3, Z = 4, d calcd = 1.301 g/cm3, F(000) = 432, 2θ range 1.69–26.40°; R indices (all data): R1 = 0.0938, wR2 = 0.1850. Compound 1c Colorless solid; mp 126–127 °C (recrystallized from hexanes and EtOAc). ESI-HRMS: calcd for C14H17O3 [M+ + 1]: 233.1178; found: 233.1182. 1H NMR (400 MHz, CDCl3): δ = 7.06 (s, 1 H), 4.11 (dd, J = 5.2, 5.6 Hz, 2 H), 3.83 (s, 3 H), 2.94–2.92 (m, 2 H), 2.82–2.79 (m, 2 H), 2.63–2.60 (m, 2 H), 2.04–1.98 (m, 2 H), 1.79–1.73 (m, 2 H). 13C NMR (100 MHz, CDCl3): δ = 206.28, 155.54, 151.99, 147.87, 132.36, 131.62, 102.86, 73.48, 55.94, 36.12, 31.50, 27.90, 24.54, 24.32; Anal. Calcd for C14H16O3: C, 72.39; H, 6.94. Found: C, 72.68; H, 7.23. Single-crystal X-ray diagram shows that the crystal of compound 1c was grown by slow diffusion of EtOAc into a solution of compound 1c in CH2Cl2 to yield colorless prism. The compound crystallizes in the triclinic crystal system, space group P-1, a = 8.4193(10) Å, b = 8.6260(10) Å, c = 9.7658(12) Å, V = 593.29(12) Å3, Z = 2, d calcd = 1.300 g/cm3, F(000) = 248, 2θ range 2.25–26.38°; R indices (all data): R1 = 0.0978, wR2 = 0.1994. Compound 1f Colorless solid; mp 75–76 °C (recrystallized from hexanes and EtOAc). ESI-HRMS: m/z calcd for C13H15O2 [M+ + 1]: 203.1072; found: 203.1074. 1H NMR (400 MHz, CDCl3): δ = 7.32 (s, 1 H), 7.24 (s, 1 H), 4.02–3.98 (m, 2 H), 3.05–3.02 (m, 2 H), 2.89–2.86 (m, 2 H), 2.68–2.65 (m, 2 H), 2.00–1.95 (m, 2 H), 1.77–1.72 (m, 2 H). 13C NMR (100 MHz, CDCl3): δ = 206.36, 160.07, 150.58, 144.26, 136.50, 127.76, 115.29, 73.93, 36.89, 34.82, 32.07, 25.98, 25.10. Anal. Calcd for C13H14O2: C, 77.20; H, 6.98. Found: C, 77.39; H, 7.14. Single-crystal X-ray diagram shows that the crystal of compound 1f was grown by slow diffusion of EtOAc into a solution of compound 1f in CH2Cl2 to yield colorless prism. The compound crystallizes in the monoclinic crystal system, space group P1 21/c 1, a = 20.6470(13) Å, b = 6.1783(4) Å, c = 17.7204(10) Å, V = 2093.3(2) Å3, Z = 8, d calcd = 1.283 g/cm3, F(000) = 864, 2θ range 1.06–26.71°; R indices (all data): R1 = 0.0883, wR2 = 0.1083. Compound 1g Colorless solid; mp 107–108 °C (recrystallized from hexanes and EtOAc). ESI-HRMS: m/z calcd for C13H15O2 [M+ + 1]: 203.1072; found: 203.1076. 1H NMR (400 MHz, CDCl3): δ = 7.17 (s, 2 H), 4.00–3.98 (m, 2 H), 3.46–3.43 (m, 2 H), 2.99–2.96 (m, 2 H), 2.68–2.65 (m, 2 H), 2.00–1.95 (m, 2 H), 1.74–1.67 (m, 2 H). 13C NMR (100 MHz, CDCl3): δ = 207.91, 160.25, 150.89, 135.42, 134.41, 127.42, 124.38, 73.42, 37.69, 32.17, 24.90, 24.55, 24.20. Anal. Calcd for C13H14O2: C, 77.20; H, 6.98. Found: C, 77.41; H, 6.76. Single-crystal X-ray diagram shows that the crystal of compound 1g was grown by slow diffusion of EtOAc into a solution of compound 1g in CH2Cl2 to yield colorless prism. The compound crystallizes in the monoclinic crystal system, space group P1 21/n 1, a = 9.0400(9) Å, b = 8.6174(9) Å, c = 13.6389(14) Å, V = 1044.01(18) Å3, Z = 4, d calcd = 1.287 g/cm3, F(000) = 432, 2θ range 2.50–26.37°; R indices (all data): R1 = 0.0630, wR2 = 0.1108
  • 15 Isabelle ME, Wightman RH, Avdovich HW, Laycock DE. Can. J. Chem. 1980; 58: 1344
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  • References and Notes

    • 6a Aono T, Kishimoto S, Araki Y, Noguchi S. Chem. Pharm Bull. 1978; 26: 1776
      CrossrefSearch in Google Scholar
    • 6b Schuler G, Gorls H, Boland W. Eur. J. Org. Chem. 2001; 1663
    • 6c Girijia T, Shanker PS, Subba RaoG. S. R. J. Chem. Soc., Perkin Trans. 1 1991; 1467
    • 6d Lauchli R, Schuler G, Boland W. Phytochemistry 2002; 61: 807
      CrossrefSearch in Google Scholar
  • 8 Chattopadhyay SK, Biswas T, Maity S. Synlett 2006; 2211
    Thieme Connect
  • 9 Tsai J.-C, Li S.-R, Chen L.-Y, Chen PY, Jhong JY, Shu C.-J, Lo Y.-F, Lin C.-N, Wang E.-C. J. Chin. Chem. Soc. 2008; 55: 1317
    Search in Google Scholar

    • For Friedel–Crafts acylation reaction, see:

    • 12a Heaney H In Comprehensive Organic Synthesis. Vol. 2. Trost BM, Fleming I. Pergamon Press; Oxford: 1991: 733
      CrossrefSearch in Google Scholar
    • 12b Olah GA. Friedel–Crafts Chemistry. John Wiley and Sons; New York: 1973
      Search in Google Scholar
    • 12c For reviews on the intramolecular Friedel–Crafts acylation reaction, see: Heaney H. In Comprehensive Organic Synthesis. Vol. 2. Trost BM, Fleming I. Pergamon Press; Oxford: 1991: 753
      CrossrefSearch in Google Scholar
    • 12d Sethna S In Friedel–Crafts and Related Reactions. Vol. 3. Olah GA. Interscience; New York: 1964: 911
      Search in Google Scholar
  • 13 CCDC 846976 (1a), 845967 (1c), 853005 (1f), 853004 (1g), and 845966 (7) contain the supplementary crystallographic data for this paper. This data can be obtained free of charge via www.ccdc.cam.ac.uk/conts/retrieving.html [or from the CCDC, 12 Union Road, Cambridge CB2 1EZ, UK; fax: +44(1223)336033; e-mail: deposit@ccdc.cam.ac.uk ]
  • 14 Representative Synthetic Transformation of Skeleton 1 from 5 A solution of 5 (0.4 mmol) and aq NaOH (6 M, 5 mL) in THF (10 mL) was refluxed for 6 h. The reaction was traced by TLC until 5 was completely consumed. The reaction solution was cooled to r.t. and concentrated until one third of the solution remained. The remained solution was extracted with EtOAc (3 × 10 mL). The aqueous phase was cooled in an ice-bath and acidified by adding concentrated aq HCl to pH 2. The aqueous solution was extracted with EtOAc (3 × 20 mL), and the extracts were washed with brine. The combined organic layers were washed with brine, dried, filtered, and evaporated to afford a crude acid product under reduced pressure. Without purification, PPA (3 mL) was added to a solution of the crude acid product in CH2Cl2 (5 mL) at r.t. The reaction mixture was stirred at r.t. for 4 h. Saturated aq NaHCO3 (10 mL) was added to the reaction mixture, and the residue was extracted with CH2Cl2 (3 × 30 mL). The combined organic layers were washed with brine, dried, filtered, and evaporated to afford the crude product under reduced pressure. Purification on silica gel (hexanes–EtOAc = 3:1) afforded skeleton 1. Representative Data for Compound 1a Colorless solid; mp 135–136 °C (recrystallized from hexanes and EtOAc). ESI-HRMS: m/z ] calcd for C13H15O2 203.1072 [M+ + 1; found: 203.1073. 1H NMR (400 MHz, CDCl3): δ = 7.54 (d, J = 8.0 Hz, 1 H), 6.98 (d, J = 8.0 Hz, 1 H), 4.10 (dd, J = 5.2, 5.6 Hz, 2 H), 3.02 (t, J = 5.6 Hz, 2 H), 2.85–2.82 (m, 2 H), 2.69–2.66 (m, 2 H), 2.05–1.99 (m, 2 H), 1.82–1.76 (m, 2 H). 13C NMR (100 MHz, CDCl3): δ = 205.94, 166.03, 155.93, 132.40, 131.52, 122.75, 121.61, 77.31, 73.29, 36.48, 31.60, 27.83, 24.88. Anal. Calcd for C13H14O2: C, 77.20; H, 6.98. Found: C, 77.51; H, 7.34. Single-crystal X-ray diagram shows that the crystal of compound 1a was grown by slow diffusion of EtOAc into a solution of compound 1a in CH2Cl2 to yield colorless prism. The compound crystallizes in the triclinic crystal system, space group P-1, a = 8.4928(2) Å, b = 10.5935(2) Å, c = 12.4192(2) Å, V = 1032.67(4) Å3, Z = 4, d calcd = 1.301 g/cm3, F(000) = 432, 2θ range 1.69–26.40°; R indices (all data): R1 = 0.0938, wR2 = 0.1850. Compound 1c Colorless solid; mp 126–127 °C (recrystallized from hexanes and EtOAc). ESI-HRMS: calcd for C14H17O3 [M+ + 1]: 233.1178; found: 233.1182. 1H NMR (400 MHz, CDCl3): δ = 7.06 (s, 1 H), 4.11 (dd, J = 5.2, 5.6 Hz, 2 H), 3.83 (s, 3 H), 2.94–2.92 (m, 2 H), 2.82–2.79 (m, 2 H), 2.63–2.60 (m, 2 H), 2.04–1.98 (m, 2 H), 1.79–1.73 (m, 2 H). 13C NMR (100 MHz, CDCl3): δ = 206.28, 155.54, 151.99, 147.87, 132.36, 131.62, 102.86, 73.48, 55.94, 36.12, 31.50, 27.90, 24.54, 24.32; Anal. Calcd for C14H16O3: C, 72.39; H, 6.94. Found: C, 72.68; H, 7.23. Single-crystal X-ray diagram shows that the crystal of compound 1c was grown by slow diffusion of EtOAc into a solution of compound 1c in CH2Cl2 to yield colorless prism. The compound crystallizes in the triclinic crystal system, space group P-1, a = 8.4193(10) Å, b = 8.6260(10) Å, c = 9.7658(12) Å, V = 593.29(12) Å3, Z = 2, d calcd = 1.300 g/cm3, F(000) = 248, 2θ range 2.25–26.38°; R indices (all data): R1 = 0.0978, wR2 = 0.1994. Compound 1f Colorless solid; mp 75–76 °C (recrystallized from hexanes and EtOAc). ESI-HRMS: m/z calcd for C13H15O2 [M+ + 1]: 203.1072; found: 203.1074. 1H NMR (400 MHz, CDCl3): δ = 7.32 (s, 1 H), 7.24 (s, 1 H), 4.02–3.98 (m, 2 H), 3.05–3.02 (m, 2 H), 2.89–2.86 (m, 2 H), 2.68–2.65 (m, 2 H), 2.00–1.95 (m, 2 H), 1.77–1.72 (m, 2 H). 13C NMR (100 MHz, CDCl3): δ = 206.36, 160.07, 150.58, 144.26, 136.50, 127.76, 115.29, 73.93, 36.89, 34.82, 32.07, 25.98, 25.10. Anal. Calcd for C13H14O2: C, 77.20; H, 6.98. Found: C, 77.39; H, 7.14. Single-crystal X-ray diagram shows that the crystal of compound 1f was grown by slow diffusion of EtOAc into a solution of compound 1f in CH2Cl2 to yield colorless prism. The compound crystallizes in the monoclinic crystal system, space group P1 21/c 1, a = 20.6470(13) Å, b = 6.1783(4) Å, c = 17.7204(10) Å, V = 2093.3(2) Å3, Z = 8, d calcd = 1.283 g/cm3, F(000) = 864, 2θ range 1.06–26.71°; R indices (all data): R1 = 0.0883, wR2 = 0.1083. Compound 1g Colorless solid; mp 107–108 °C (recrystallized from hexanes and EtOAc). ESI-HRMS: m/z calcd for C13H15O2 [M+ + 1]: 203.1072; found: 203.1076. 1H NMR (400 MHz, CDCl3): δ = 7.17 (s, 2 H), 4.00–3.98 (m, 2 H), 3.46–3.43 (m, 2 H), 2.99–2.96 (m, 2 H), 2.68–2.65 (m, 2 H), 2.00–1.95 (m, 2 H), 1.74–1.67 (m, 2 H). 13C NMR (100 MHz, CDCl3): δ = 207.91, 160.25, 150.89, 135.42, 134.41, 127.42, 124.38, 73.42, 37.69, 32.17, 24.90, 24.55, 24.20. Anal. Calcd for C13H14O2: C, 77.20; H, 6.98. Found: C, 77.41; H, 6.76. Single-crystal X-ray diagram shows that the crystal of compound 1g was grown by slow diffusion of EtOAc into a solution of compound 1g in CH2Cl2 to yield colorless prism. The compound crystallizes in the monoclinic crystal system, space group P1 21/n 1, a = 9.0400(9) Å, b = 8.6174(9) Å, c = 13.6389(14) Å, V = 1044.01(18) Å3, Z = 4, d calcd = 1.287 g/cm3, F(000) = 432, 2θ range 2.50–26.37°; R indices (all data): R1 = 0.0630, wR2 = 0.1108
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Figure 1 Structures of oxepane, 1-indanone, and skeleton 1
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Scheme 1 Retrosynthetic route of skeleton 1
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Scheme 2 Synthesis of 6-oxacyclohepta[e]indan-3-ones 1a–c
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Equation [ 1 ] Possible PhBCl2-mediated intermediate
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Figure 2 X-ray structure of compound 1c
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Figure 3 Six skeletons of 1-indanonyl oxepanes
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Scheme 3 Synthesis of 5-oxacyclohepta[f]indan-1-ones 1d–e
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Scheme 4 Synthesis of 5-oxacyclohepta[f]indan-3-one 1f and 6-oxacyclohepta[e]indan-1-one 1g
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Scheme 5 Synthesis of 10-oxacyclohepta[e]indan-3-one 1h
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Scheme 6 One-pot combination reaction of compound 3c