Download PDF
Synthesis 2010(18): 3204-3210  
DOI: 10.1055/s-0030-1258172
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

Phosphazene Base-Catalyzed Intramolecular Cascade Reactions of Aryl-Substituted Enynes

Jian-Sheng Tanga,b, Ye-Xiang Xiea, Zhi-Qiang Wanga, Chen-Liang Denga, Jin-Heng Li*a
a Key Laboratory of Chemical Biology & Traditional Chinese Medicine Research (Ministry of Education), Hunan Normal University, Changsha 410081, P. R. of China
Fax: +86(731)88872101; e-Mail: jhli@hunnu.edu.cn;
b Mathematics and Science Department, Hunan First Normal University, Changsha, 410205, P. R. of China

Further Information

Publication History

Received 6 April 2010
Publication Date:
12 July 2010 (online)

 PDF Download Permissions and Reprints All articles of this category

Abstract

A novel method for the synthesis of 9-aryl-3a,4-dihydronaphtho[2,3-c]furan-1(3H)-ones has been developed by P4-t-Bu-catalyzed intramolecular cascade reactions of enynes. In the presence of a catalytic amount of phosphazene P4-t-Bu base, a variety of 3-arylallyl 3-arylpropiolates underwent the cascade cyclization reaction smoothly in moderate to excellent yields.

Key words

P4-t-Bu base - cascade cyclization reaction - 9-aryl-3a,4-dihydronaphtho[2,3-c]furan-1(3H)-one - 3-arylallyl 3-arylpropiolate

The cascade reaction strategy is of continuing interesting in the field of organic chemistry because it is a valuable route for the synthesis of polysubstituted polycyclic compounds. [¹-³] Our interest is focused on the intramolecular Diels-Alder reactions of aryl-substituted enynes 1, which proceeds via a cascade cyclization process (Scheme  [¹] ). Traditionally, there are two transformations for these purposes: one involves acetic anhydride mediated cyclization via the activation of the ortho-arene C-H bond at the terminal alkene (Scheme  [¹] ), [²] and the other is acetic anhydride [²h] or base-mediated cyclization employing the ortho-arene C-H bond at the terminal alkyne as a reaction partner. [³] For example, Klemm and Gopinath described intramolecular Diels-Alder cyclization of 3,4-(methylenedioxy)cinnamyl 3,4,5-trimethoxyphenylpropiolate to afford γ-apopicropodophyllin in 48% yield using acetic anhydride as the catalyst and solvent. [²a] In 1972, Laird and Ollis employed allylpropynyl ammonium cations as the substrates, shifting regioselectivity toward the ortho-arene­ C-H bond at the terminal alkyne in the presence of excess sodium methoxide. [³a] Subsequently, several papers have been reported that extend these routes in organic synthesis, but the scope has not yet been examined and it is often restricted to special substrates with unsatisfactory yields. Moreover, the high acetic anhydride or base loadings, resulting in toxic byproducts, hardly make the two transformations attractive procedures. Therefore, the development of a novel, catalytic route for the intramolecular cascade cyclization of enynes remains a challenging area. Here, we report the first intramolecular cascade cyclization protocol for the synthesis of 9-aryl-3a,4-dihydronaphtho[2,3-c]furan-1(3H)-one using a catalytic amount of P4-t-Bu (commercially available) (Scheme  [¹] ). [4] [5] It is noteworthy that these products are a prevalent motif in many naturally occurring and biologically active compounds, such as the known antiviral and antitumor agents daurinol and retrochinensin. [6]

Scheme 1 Intramolecular cascade reactions

Table 1 Screening Optimal Conditionsa

Entry Base (equiv) Solvent Temp (˚C) Isolated yield (%)
 1 K2CO3 (2) DCE 100 20
 2 K2CO3 (4) DCE 100 52
 3 K2CO3 (5) DCE 100 80
 4 K2CO3 (6) DCE 100 75
 5 Cs2CO3 (5) DCE 100 44
 6 K3PO4 (5) DCE 100 61
 7 NaOH (5) DCE 100 trace
 8 NaOEt (5) DCE 100 70
 9 DABCO (5) DCE 100 20
10 DBU (5) DCE 100 35
11b P4-t-Bu (0.05) DCE 100 52
12b P4-t-Bu (0.1) DCE 100 82
13b P4-t-Bu (0.2) DCE 100 46
14b P1 (0.1) DCE 100 80
15b Ph3P (0.1) DCE 100 trace
16 K2CO3 (5) toluene 100 45
17 K2CO3 (5) THF 100 53
18 K2CO3 (5) DMF 100 trace
19 K2CO3 (5) DCE  80 34
20 K2CO3 (5) DCE 120 65
a Conditions: 1a (0.2 mmol), base, solvent (2 mL), 24 h.
b For 60 h.

Our initial investigation began with the cyclization of cinnamyl 3-phenylpropiolate (1a) to optimize the reaction conditions (Table  [¹] ). Generally, base-mediated intramolecular Diels-Alder reactions of aryl-substituted enyne 1a are used with the ortho-arene C-H bond at the terminal alkyne as a reaction partner. [³] However, we found that only product 2a was obtained by activating the ortho-arene C-H bond at the terminal alkene using various bases (entries 1-13). The results demonstrated that the amount of potassium carbonate affected the reaction (entries 1-4). While treatment of substrate 1a with two equivalents of potassium carbonate afforded the target product 2a in 20% yield (entry 1), 5 equivalents of potassium carbonate enhanced the yield to 80% (entry 3), and an identical result was obtained in the presence of six equivalents of potassium carbonate (entry 4). Prompted by these results, a variety of other bases, such as Cs2CO3, K3PO4, NaOH, NaOEt, DABCO, DBU, and P4-t-Bu, were examined (entries 5-13). We found that all but one were inferior to potassium carbonate (entries 5-10). To our delight, 10 mol% of P4-t-Bu, an organic superbase, gave the best results after prolonged the reaction time (entry 12). Identical results were observed using P1 (BEMP) base (entry 14). Triphenylphosphine was also evaluated as the catalyst, however, no reaction occurred (entry 15). Subsequently, a number of other solvents, including toluene, tetrahydrofuran, and N,N-dimethylformamide, were tested, and they were less effective than 1,2-dichloroethane (entries 16-18). Finally, the effect of the reaction temperature was evaluated, and it turned out that both 80 ˚C and 120 ˚C decreased the yield (entries 19 and 20). The structure of 2a was unambiguously confirmed by X-ray single-crystal diffraction analysis (Figure  [¹] ). [7]

Figure 1 ORTEP diagram of the single-crystal X-ray structure of compound 2a

With the optimized reaction conditions in hand, the enyne scope was investigated (Table  [²] ). [8] Initially, a series of 3-arylallyl 3-phenylpropiolates 1b-d, bearing electron-rich or electron-deficient arylallyl groups, were treated with P4-t-Bu smoothly in good yields (entries 1-3). Gratifyingly, a moderate yield of 2e was still isolated from heteroarylallyl substrate 1e (entry 4). The results showed that several functional groups, such as methyl, methoxy, iodo, bromo, fluoro, acetyl, and nitro groups, on the aryl ring of the 3-arylpropiolate moiety were tolerated (entries 5-15). The cyclization reaction of substrates 1f-h with a p-, m-, or o-methyl group, for instance, successfully proceeded with P4-t-Bu in moderate yields (entries 5-7). It is pleasing to observe that the optimized conditions were compatible with halo-substituted substrates 1k-m (entries 10-12). Electron-deficient substrates 1n-p also underwent the cyclization reaction with P4-t-Bu in excellent yields (entries 13-15). It was noted that cinnamyl 3-(thiophen-2-yl)propiolate (1q) was suitable for the reaction, affording the corresponding product 2q in 90% yield (entry 16). In the presence of P4-t-Bu, two N-cinnamyl-3-phenylpropiolamides 1r and 1s were also consistent with the reaction conditions, and they were transformed into the desired products 2r and 2s in 70% and 81% yields, respectively (entries 17 and 18). However, (E)-[3-(cinnamyloxy)prop-1-ynyl]benzene was not a suitable substrate under the optimized conditions.

Table 2 P4-t-Bu-Catalyzed Intramolecular Cyclization Reactions of Enynes 1 a (continued)
Entry Enyne 1 Product 2 Yieldb (%)
 1

1b

2b 		92
 2

1c

2c 		72
 3

1d

2d 		80
 4

1e

2e 		63

 5 R = 4-Me 1f R = 4-Me 2f 61
 6 R = 3-Me 1g R = 3-Me 2g 60
 7 R = 2-Me 1h R = 2-Me 2h 55
 8 R = 4-OMe 1i R = 4-OMe 2i 86
 9 R = 2-OMe 1j R = 2-OMe 2j 92
10 R = 4-I 1k R = 4-I 2k 48
11 R = 2-Br 1l R = 2-Br 2l 91
12 R = 4-F 1m R = 4-F 2m 54
13 R = 4-Ac 1n R = 4-Ac 2n 91
14 R = 3-Ac 1o R = 3-Ac 2o 98
15 R = 3-NO2 1p R = 3-NO2 2p 92
16

1q

2q 		90
17

1r

2r 		70
18

1s

2s 		81
a Reaction conditions: 1 (0.2 mmol), P4-t-Bu (10 mol%), DCE (2 mL), 100 ˚C, 60 h.
b Isolated yield.

Compared with the results for the base-mediated intramolecular Diels-Alder reactions of aryl-substituted enynes 1, [³] different chemoselectivity was observed in the present reaction: the chemoselectivity was shifted towards the ortho-arene C-H bond at the terminal alkene, which is identical to the acetic anhydride mediated cyclization process. Thus, we deduced that the present reaction proceeds via a Diels-Alder mechanism, [²] and the role of P4-t-Bu base is as an acid scavenger that promotes the reaction by a proton-transfer process (Scheme  [²] ).

Scheme 2 A possible mechanism

In summary, we have disclosed phosphazene P4-t-Bu base as an efficient catalyst for the intramolecular cascade cyclization of enynes. This work is the first to demonstrate that the intramolecular Diels-Alder cyclization reaction of enynes can be carried out successfully using a catalytic amount of phosphazene P4-t-Bu base. Importantly, this new route allows the base-catalyzed mediated intramolecular cascade cyclization of enynes by activating the ortho-arene C-H bond at the terminal alkene, not the ortho-arene­ C-H bond at the terminal alkyne. [³]

NMR spectroscopy was performed on a Bruker-500 spectrometer operating at 500 MHz (¹H NMR) and 125 MHz (¹³C NMR), TMS internal standard and CDCl3 solvent. MS analysis was performed by GC-MS analysis (Shimadzu GCMS-QP2010 plus). Melting points are uncorrected.

Phosphazene Base Catalyzed Intramolecular Cascade Reactions of Aryl-Substituted Enynes; Typical Procedure

3-Arylallyl 3-arylpropiolate 1 (0.2 mmol), P4-t-Bu (10 mol%), and DCE (2 mL) were added to a Schlenk tube and the soln was stirred at 100 ˚C for the indicated time until complete consumption of starting material (TLC and GC-MS monitoring). When the reaction was finished, the mixture was washed with brine and extracted with Et2O. The combined extracts were dried (anhyd Na2SO4) and evaporated in vacuo. The residue was purified by flash column chromatography (silica gel, hexane-EtOAc) to afford the desired product.

9-Phenyl-3a,4-dihydronaphtho[2,3- c ]furan-1(3 H )-one (2a) [6e]

White solid; mp 182.1-183.3 ˚C.

IR (KBr): 1748 cm-¹.

¹H NMR (500 MHz, CDCl3): δ = 7.46-7.38 (m, 3 H), 7.34-7.29 (m, 4 H), 7.18 (t, J = 7.5 Hz, 1 H), 6.95 (d, J = 8.0 Hz, 1 H), 4.73 (t, J = 9.0 Hz, 1 H), 4.04 (t, J = 8.5 Hz, 1 H), 3.50-3.42 (m, 1 H), 3.07, 3.05 (dd, J = 6.5, 6.5 Hz, 1 H), 2.90, 2.87 (dd, J = 15.0, 15.0 Hz, 1 H).

¹³C NMR (125 MHz, CDCl3): δ = 168.2, 147.3, 135.9, 135.4, 134.2, 129.8, 129.1, 128.5, 128.0, 127.8, 127.2, 126.4, 122.1, 71.2, 35.5, 33.0.

LRMS (EI, 70 eV): m/z (%) = 262 (M+, 100), 231 (46), 217 (72), 203 (70), 101 (41).

7-Methyl-9-phenyl-3a,4-dihydronaphtho[2,3- c ]furan-1(3 H )-one (2b)

White solid; mp 165.8-167.0 ˚C.

IR (KBr): 1748 cm-¹.

¹H NMR (500 MHz, CDCl3): δ = 7.45-7.44 (m, 3 H), 7.29-7.26 (m, 2 H), 7.17 (d, J = 7.5 Hz, 1 H), 7.11 (d, J = 8.0 Hz, 1 H), 6.75 (s, 1 H), 4.71 (t, J = 9.0 Hz, 1 H), 4.03 (t, J = 8.5 Hz, 1 H), 3.46-3.38 (m, 1 H), 3.03, 3.01 (dd, J = 6.5, 6.5 Hz, 1 H), 2.84, 2.81 (dd, J = 15.5, 15.5 Hz, 1 H), 2.22 (s, 3 H).

¹³C NMR (125 MHz, CDCl3): δ = 168.3, 147.5, 136.9, 135.8, 134.3, 132.4, 130.5, 129.7, 128.5, 128.0, 127.9, 127.8, 122.1, 71.1, 35.8, 32.7, 21.1.

LRMS (EI, 70 eV): m/z (%) = 276 (M+, 53), 215 (27), 202 (29), 71 (77), 57 (100), 43 (98).

HRMS (EI): m/z [M]+ calcd for C19H16O2: 276.1150; found: 276.1148.

7-Methoxy-9-phenyl-3a,4-dihydronaphtho[2,3- c ]furan-1(3 H )-one (2c) [8]

White solid; mp 142.0-143.8 ˚C.

IR (KBr): 1745 cm-¹.

¹H NMR (500 MHz, CDCl3): δ = 7.43-7.42 (m, 3 H), 7.31-7.29 (m, 2 H), 7.19 (d, J = 7.5 Hz, 1 H), 6.85-6.83 (m, 1 H), 6.50 (d, J = 2.5 Hz, 1 H), 4.71 (t, J = 9.0 Hz, 1 H), 4.03 (t, J = 7.5 Hz, 1 H), 3.65 (s, 3 H), 3.46-3.38 (m, 1 H), 3.02, 2.99 (dd, J = 7.0, 6.5 Hz, 1 H), 2.81, 2.77 (dd, J = 15.0, 15.0 Hz, 1 H).

¹³C NMR (125 MHz, CDCl3): δ = 168.2, 158.7, 147.2, 137.0, 134.1, 129.7, 128.7, 128.5, 127.8, 127.4, 122.6, 115.3, 114.6, 71.1, 55.3, 35.9, 32.1.

LRMS (EI, 70 eV): m/z (%) = 292 (M+, 100), 247 (47), 231 (14), 215 (28), 203 (20).

7-Nitro-9-phenyl-3a,4-dihydronaphtho[2,3- c ]furan-1(3 H )-one (2d)

Yellow solid; mp 188.0-189.9 ˚C.

IR (KBr): 1748 cm-¹.

¹H NMR (500 MHz, CDCl3): δ = 8.16-8.14 (m, 1 H), 7.80 (d, J = 2.5 Hz, 1 H), 7.49-7.46 (m, 4 H), 7.30-7.26 (m, 2 H), 4.76 (t, J = 7.5 Hz, 1 H), 4.08 (t, J = 9.0 Hz, 1 H), 3.55-3.47 (m, 1 H), 3.23, 3.20 (dd, J = 6.5, 6.5 Hz, 1 H), 2.97, 2.94 (dd, J = 15.5, 15.5 Hz, 1 H).

¹³C NMR (125 MHz, CDCl3): δ = 167.3, 147.5, 145.3, 142.3, 137.4, 132.6, 130.0, 129.3, 128.9, 128.3, 124.4, 124.3, 123.4, 70.9, 35.2, 32.8.

LRMS (EI, 70 eV): m/z (%) = 307 (M+, 100), 290 (33), 260 (17), 215 (36), 101 (35).

HRMS (EI): m/z [M]+ calcd for C18H13NO4: 307.0845; found: 307.0848.

4-Phenyl-7a,8-dihydrothieno[2,3-f][2]benzofuran-5(7H)-one (2e) [6e]

Yellow solid; mp 136.5-138.0 ˚C.

IR (KBr): 1748 cm-¹.

¹H NMR (500 MHz, CDCl3): δ = 7.51-7.49 (m, 1 H), 7.48-7.38 (m, 4 H), 7.07 (t, J = 6.0 Hz, 1 H), 6.72 (d, J = 5.0 Hz, 1 H), 4.71 (t, J = 7.5 Hz, 1 H), 4.05 (t, J = 9.0 Hz, 1 H), 3.69-3.60 (m, 1 H), 3.24, 3.20 (dd, J = 8.0, 7.5 Hz, 1 H), 2.85, 2.81 (dd, J = 16.5, 16.5 Hz, 1 H).

¹³C NMR (125 MHz, CDCl3): δ = 168.0, 144.2, 139.2, 138.1, 134.3, 129.4, 128.8, 127.8, 126.8, 122.9, 117.5, 70.5, 37.4, 27.8.

LRMS (EI, 70 eV): m/z (%) = 268 (M+, 38), 223 (33), 165 (11), 43 (100).

9-(4-Tolyl)-3a,4-dihydronaphtho[2,3- c ]furan-1(3 H )-one (2f)

White solid; mp 151.1-152.8 ˚C.

IR (KBr): 1748 cm-¹.

¹H NMR (500 MHz, CDCl3): δ = 7.30-7.26 (m, 2 H), 7.26-7.20 (m, 2 H), 7.20-7.17 (m, 3 H), 6.99 (d, J = 7.5 Hz, 1 H), 4.72 (t, J = 9.0 Hz, 1 H), 4.04 (t, J = 7.5 Hz, 1 H), 3.48-3.40 (m, 1 H), 3.06, 3.01 (dd, J = 6.5, 6.5 Hz, 1 H), 2.88, 2.86 (dd, J = 15.5, 15.5 Hz, 1 H), 2.42 (s, 3 H).

¹³C NMR (125 MHz, CDCl3): δ = 168.3, 147.6, 138.4, 136.1, 135.5, 131.2, 129.7, 129.2, 128.7, 128.0, 127.2, 121.8, 71.1, 35.6, 33.1, 21.4.

LRMS (EI, 70 eV): m/z (%) = 276 (M+, 100), 231 (98), 217 (58), 202 (60), 101 (26).

HRMS (EI): m/z [M]+ calcd for C19H16O2: 276.1150; found: 276.1149.

9-(3-Tolyl)-3a,4-dihydronaphtho[2,3- c ]furan-1(3 H )-one (2g)

White solid; mp 152.2-153.0 ˚C.

IR (KBr): 1748 cm-¹.

¹H NMR (500 MHz, CDCl3): δ = 7.34-7.24 (m, 3 H), 7.22-7.19 (m, 1 H), 7.18-7.09 (m, 3 H), 6.97 (d, J = 8.0 Hz, 1 H), 4.72 (t, J = 7.5 Hz, 1 H), 4.03 (t, J = 8.0 Hz, 1 H), 3.48-3.40 (m, 1 H), 3.06, 3.03, (dd, J = 6.5, 6.5 Hz, 1 H), 2.88, 2.85 (dd, J = 15.5, 15.5 Hz, 1 H), 2.38 (s, 3 H).

¹³C NMR (125 MHz, CDCl3): δ = 168.2, 147.5, 137.4, 136.0, 135.4, 134.2, 129.8, 129.3, 129.2, 128.0, 127.8, 127.2, 122.0, 71.7, 35.6, 33.1, 21.4.

LRMS (EI, 70 eV): m/z (%) = 276 (M+, 100), 231 (93), 215 (49), 202 (62), 101 (23).

HRMS (EI): m/z [M]+ calcd for C19H16O2: 276.1150; found: 276.1145.

9-(2-Tolyl)-3a,4-dihydronaphtho[2,3- c ]furan-1(3 H )-one (2h)

White solid; mp 126.9-128.2 ˚C.

IR (KBr): 1748 cm-¹.

¹H NMR (500 MHz, CDCl3): δ = 7.32-7.26 (m, 4 H), 7.22-7.14 (m, 2 H), 6.91 (d, J = 7.5 Hz, 1 H), 6.80 (d, J = 8.0 Hz, 1 H), 4.74 (t, J = 6.5 Hz, 1 H), 4.07 (t, J = 9.0 Hz, 1 H), 3.51-3.46 (m, 1 H), 3.09, 3.08 (dd, J = 3.0, 3.5 Hz, 1 H), 2.92, 2.88 (dd, J = 16.0, 15.0 Hz, 1 H), 2.24 (s, 3 H).

¹³C NMR (125 MHz, CDCl3): δ = 168.1, 168.0, 146.2, 137.0, 135.4, 135.2, 135.1, 134.7, 134.0, 131.2, 130.2, 130.1, 130.0, 129.9, 129.7, 128.6, 128.5, 128.2, 128.2, 128.0, 127.9, 127.7, 127.5, 126.5, 125.8, 125.4, 123.0, 122.7, 71.4, 35.3, 32.8, 19.5.

LRMS (EI, 70 eV): m/z (%) = 276 (M+, 74), 231 (100), 215 (84), 202 (63), 101 (21).

HRMS (EI): m/z [M]+ calcd for C19H16O2: 276.1150; found: 276.1148.

9-(4-Methoxyphenyl)-3a,4-dihydronaphtho[2,3- c ]furan-1(3 H )-one (2i)

White solid; mp 130.0-131.5 ˚C.

IR (KBr): 1748 cm-¹.

¹H NMR (500 MHz, CDCl3): δ = 7.32-7.26 (m, 4 H), 7.20-7.17 (m, 1 H), 7.01 (d, J = 7.5 Hz, 1 H), 6.96 (d, J = 7.5 Hz, 2 H), 4.72 (t, J = 8.5 Hz, 1 H), 4.04 (t, J = 8.5 Hz, 1 H), 3.86 (s, 3 H), 3.45-3.40 (m, 1 H), 3.05, 3.02 (dd, J = 6.5, 6.5 Hz, 1 H), 2.88, 2.85 (dd, J = 15.5, 15.5 Hz, 1 H).

¹³C NMR (125 MHz, CDCl3): δ = 168.4, 159.9, 147.4, 136.2, 135.6, 131.5, 129.8, 129.3, 128.0, 127.2, 126.2, 121.4, 113.2, 71.1, 55.2, 35.7, 33.1.

LRMS (EI, 70 eV): m/z (%) = 292 (M+, 100), 261 (10), 247 (62), 203 (32), 189 (39).

HRMS (EI): m/z [M]+ calcd for C19H16O3: 292.1099; found: 292.1105.

9-(2-Methoxyphenyl)-3a,4-dihydronaphtho[2,3- c ]furan-1(3 H )-one (2j)

Colorless oil.

IR (KBr): 1748 cm-¹.

¹H NMR (500 MHz, CDCl3): δ = 7.42-7.39 (m, 1 H), 7.29-7.26 (m, 2 H), 7.14-7.09 (m, 1 H), 7.00-6.91 (m, 4 H), 4.70 (t, J = 8.5 Hz, 1 H), 4.05 (t, J = 9.0 Hz, 1 H), 3.55-3.38 (m, 1 H), 3.07-3.02 (m, 1 H), 3.00-2.86 (m, 1 H), 2.04 (s, 3 H).

¹³C NMR (125 MHz, CDCl3): δ = 171.1, 168.3, 167.9, 157.8, 156.4, 144.5, 142.9, 135.5, 135.4, 135.3, 134.8, 131.9, 130.0, 129.8, 129.6, 129.6, 129.4, 128.6, 128.0, 127.5, 127.3, 127.0, 124.0, 123.4, 123.0, 122.8, 120.4, 120.1, 111.1, 111.0, 71.2, 71.2, 55.7, 55.5, 35.4, 35.3, 32.9, 32.8.

LRMS (EI, 70 eV): m/z (%) = 292 (M+, 100), 261 (41), 247 (31), 231 (43), 215 (23), 202 (36), 101 (22).

HRMS (EI): m/z [M]+ calcd for C19H16O3: 292.1099; found: 292.1100.

9-(4-Iodophenyl)-3a,4-dihydronaphtho[2,3- c ]furan-1(3 H )-one (2k)

Yellow solid; mp 223.7-225.1 ˚C.

IR (KBr): 1748 cm-¹.

¹H NMR (500 MHz, CDCl3): δ = 7.77 (d, J = 8.5 Hz, 2 H), 7.33-7.28 (m, 2 H), 7.18 (t, J = 8.5 Hz, 1 H), 7.06-7.03 (m, 2 H), 6.93 (d, J = 8.0 Hz, 1 H), 4.73 (t, J = 8.5 Hz, 1 H), 4.04 (t, J = 8.0 Hz, 1 H), 3.48-3.40 (m, 1 H), 3.07, 3.04 (dd, J = 7.0, 7.0 Hz, 1 H), 2.88, 2.85 (dd, J = 16.0, 15.0 Hz, 1 H).

¹³C NMR (125 MHz, CDCl3): δ = 168.1, 146.1, 137.0, 135.4, 133.7, 131.7, 130.1, 128.9, 128.2, 127.4, 122.5, 94.8, 71.2, 35.6, 32.9.

LRMS (EI, 70 eV): m/z (%) = 388 (M+, 100), 231 (34), 217 (39), 202 (73), 101 (30).

HRMS (EI): m/z [M]+ calcd for C18H13IO2: 387.9960; found: 387.9956.

9-(2-Bromophenyl)-3a,4-dihydronaphtho[2,3- c ]furan-1(3 H )-one (2l)

Pale-yellow solid; mp 137.5-139.0 ˚C.

IR (KBr): 1748 cm-¹.

¹H NMR (500 MHz, CDCl3): δ = 7.48-7.40 (m, 8 H), 4.31-4.27 (m, 1 H), 4.22-4.17 (m, 1 H), 4.05-4.02 (m, 1 H), 3.94, 3.92 (dd, J = 3.5, 5.0 Hz, 1 H), 3.80, 3.79 (dd, J = 8.5, 8.5 Hz, 1 H).

¹³C NMR (125 MHz, CDCl3): δ = 167.9, 145.5, 135.4, 135.1, 134.4, 132.9, 132.5, 131.6, 129.9, 128.2, 127.4, 126.9, 124.2, 123.8, 122.1, 71.4, 35.3, 32.7.

LRMS (EI, 70 eV): m/z (%) = 342 (M+ + 2, 1), 340 (M+, 1), 261 (100), 233 (10), 215 (15), 202 (68).

HRMS (EI): m/z [M]+ calcd for C18H13BrO2: 340.0099; found: 340.0093.

9-(4-Fluorophenyl)-3a,4-dihydronaphtho[2,3- c ]furan-1(3 H )-one (2m)

Yellow solid; mp 175.1-176.9 ˚C.

IR (KBr): 1748 cm-¹.

¹H NMR (500 MHz, CDCl3): δ = 7.34-7.28 (m, 4 H), 7.26-7.24 (m, 1 H), 7.21-7.10 (m, 2 H), 6.94 (d, J = 7.5 Hz, 1 H), 4.74 (t, J = 9.0 Hz, 1 H), 4.05 (t, J = 8.5 Hz, 1 H), 3.49-3.41 (m, 1 H), 3.07, 3.04 (dd, J = 6.5, 7.0 Hz, 1 H), 2.89, 2.86 (dd, J = 15.5, 15.5 Hz, 1 H).

¹³C NMR (125 MHz, CDCl3): δ = 168.2, 162.9 (d, J = 246.5 Hz, 1 C), 146.3, 135.7, 135.4, 129.9, 128.9, 128.1, 127.3, 122.4, 115.0, 114.9, 71.2, 35.6, 32.9.

LRMS (EI, 70 eV): m/z (%) = 280 (M+, 100), 249 (31), 221 (74).

HRMS (EI): m/z [M]+ calcd for C18H13FO2: 280.0900; found: 280.0899.

9-(4-Acetylphenyl)-3a,4-dihydronaphtho[2,3- c ]furan-1(3 H )-one (2n)

White solid; mp 170.9-172.1 ˚C.

IR (KBr): 1741, 1678 cm-¹.

¹H NMR (500 MHz, CDCl3): δ = 8.20 (d, J = 8.5 Hz, 2 H), 7.41-7.39 (m, 2 H), 7.34-7.29 (m, 2 H), 7.19-7.16 (m, 1 H), 6.87 (d, J = 7.5 Hz, 1 H), 4.75 (t, J = 7.5 Hz, 1 H), 4.06 (t, J = 9.0 Hz, 1 H), 3.51-3.43 (m, 1 H), 3.09, 3.07 (dd, J = 6.5, 6.5 Hz, 1 H), 2.89, 2.88 (dd, J = 16.0, 15.0 Hz, 1 H), 2.65 (s, 3 H).

¹³C NMR (125 MHz, CDCl3): δ = 197.8, 168.1, 146.1, 136.8, 135.4, 134.7, 130.1, 128.8, 128.4, 128.2, 128.1, 127.6, 127.4, 123.0, 71.3, 35.6, 32.9, 26.6.

LRMS (EI, 70 eV): m/z (%) = 304 (M+, 100), 289 (72), 261 (12), 231 (48), 217 (35), 202 (62), 101 (30).

HRMS (EI): m/z [M]+ calcd for C20H16O3: 304.1099; found: 304.1097.

9-(3-Acetylphenyl)-3a,4-dihydronaphtho[2,3- c ]furan-1(3 H )-one (2o)

White solid; mp 170.0-171.6 ˚C.

IR (KBr): 1740, 1675 cm-¹.

¹H NMR (500 MHz, CDCl3): δ = 8.04-8.02 (m, 1 H), 7.90-7.83 (m, 1 H), 7.59-7.53 (m, 2 H), 7.37-7.29 (m, 2 H), 7.19-7.16 (m, 1 H), 6.69 (d, J = 9.0 Hz, 1 H), 4.74 (t, J = 8.5 Hz, 1 H), 4.06 (t, J = 6.5 Hz, 1 H), 3.52-3.44 (m, 1 H), 3.09, 3.06 (dd, J = 6.5, 6.5 Hz, 1 H), 2.91, 2.88 (dd, J = 15.5, 16.0 Hz, 1 H), 2.61 (s, 3 H).

¹³C NMR (125 MHz, CDCl3): δ = 197.7, 168.0, 146.0, 139.4, 136.9, 135.3, 135.2, 130.4, 130., 128.8, 128.2, 128.0, 127.9, 127.6, 127.4, 123.0, 71.3, 35.5, 32.8, 26.6.

LRMS (EI, 70 eV): m/z (%) = 304 (M+, 100), 289 (65), 261 (13), 217 (37), 202 (56), 101 (43).

HRMS (EI): m/z [M]+ calcd for C20H16O3: 304.1099; found: 304.1098.

9-(3-Nitrophenyl)-3a,4-dihydronaphtho[2,3- c ]furan-1(3 H )-one (2p)

Yellow solid; mp 203.0-204.3 ˚C.

IR (KBr): 1772, 1732, 1719 cm-¹.

¹H NMR (500 MHz, CDCl3): δ = 8.32-8.28 (m, 1 H), 8.18-8.10 (m, 1 H), 7.74-7.61 (m, 2 H), 7.36-7.31 (m, 2 H), 7.22-7.19 (m, 1 H), 6.86 (d, J = 8.0 Hz, 1 H), 4.77 (t, J = 8.5 Hz, 1 H), 4.09 (t, J = 9.0 Hz, 1 H), 3.52-3.48 (m, 1 H), 3.12, 3.00 (dd, J = 6.5, 6.5 Hz, 1 H), 2.93, 2.90 (dd, J = 16.0, 15.5 Hz, 1 H).

¹³C NMR (125 MHz, CDCl3): δ = 167.9, 148.0, 144.4, 135.9, 135.3, 134.8, 130.4, 129.1, 128.9, 128.5, 128.4, 127.6, 127.5, 123.9, 123.5, 71.4, 35.5, 32.7.

LRMS (EI, 70 eV): m/z (%) = 307 (M+, 88), 263 (25), 215 (29), 202 (100), 101 (21).

HRMS (EI): m/z [M]+ calcd for C18H13NO4: 307.0845; found: 307.0848.

9-(Thiophen-2-yl)-3a,4-dihydronaphtho[2,3- c ]furan-1(3 H )-one (2q)

Yellow solid; mp 128.0-130.1 ˚C.

IR (KBr): 1748 cm-¹.

¹H NMR (500 MHz, CDCl3): δ = 7.49 (d, J = 5.0 Hz, 1 H), 7.33-7.30 (m, 1 H), 7.29-7.24 (m, 3 H), 7.24-7.22 (m, 1 H), 7.14 (d, J = 9.0 Hz, 1 H), 4.71 (t, J = 8.5 Hz, 1 H), 4.04 (t, J = 8.5 Hz, 1 H), 3.47 (m, 1 H), 3.03, 3.01 (dd, J = 7.5, 6.5 Hz, 1 H), 2.87, 2.84 (dd, J = 15.0, 15.5 Hz, 1 H).

¹³C NMR (125 MHz, CDCl3): δ = 167.8, 140.1, 135.9, 133.9, 130.5, 129.1, 127.9, 127.4, 127.3, 126.7, 124.1 71.0, 36.0, 32.8.

LRMS (EI, 70 eV): m/z (%) = 268 (M+, 84), 223 (100), 209 (50), 165 (23).

HRMS (EI): m/z [M]+ calcd for C16H12O2S: 268.0558; found: 268.0554.

9-Phenyl-2-propyl-2,3,3a,4-tetrahydro-1 H -benzo[ f ]isoindol-1-one (2r)

Yellow oil.

IR (KBr): 1675 cm-¹.

¹H NMR (500 MHz, CDCl3): δ = 7.42-7.37 (m, 3 H), 7.27-7.21 (m, 4 H), 7.14 (t, J = 7.5 Hz, 1 H), 6.92 (d, J = 8.0 Hz, 1 H), 3.74-3.68 (m, 1 H), 3.37-3.32 (m, 1 H), 3.23 (d, J = 8.5 Hz, 1 H), 3.15-3.11 (m, 2 H), 3.06-3.02 (m, 1 H), 3.04, 2.82-2.79 (m, 1 H), 1.60-1.55 (m, 2 H), 0.89 (t, J = 7.0 Hz, 3 H).

¹³C NMR (125 MHz, CDCl3): δ = 166.6, 140.3, 136.6, 135.6, 135.4, 130.2, 129.7, 128.3, 128.2, 127.7, 127.7, 127.6, 60.4, 50.9, 34.0, 32.4, 20.6, 11.4.

LRMS (EI, 70 eV): m/z (%) = 304 (72), 303 (M+, 100), 302 (27), 274 (74), 260 (47), 231 (57), 215 (30), 202 (54).

HRMS (EI): m/z [M]+ calcd for C21H21NO: 303.1623; found: 303.1622.

2-Benzyl-9-phenyl-2,3,3a,4-tetrahydro-1 H -benzo[ f ]isoindol-1-one (2s)

Yellow solid; mp 135.8-138.0 ˚C.

IR (KBr): 1674 cm-¹.

¹H NMR (500 MHz, CDCl3): δ = 7.45-7.33 (m, 3 H), 7.32-7.28 (m, 4 H), 7.28-7.20 (m, 5 H), 7.18-7.12 (m, 1 H), 6.93 (d, J = 7.5 Hz, 1 H), 4.65 (d, J = 14.5 Hz, 1 H), 4.37 (d, J = 15.0 Hz, 1 H), 3.60 (t, J = 9.0 Hz, 1 H), 3.12-3.02 (m, 1 H), 3.01-2.96 (m, 2 H), 2.78, 2.75 (dd, J = 5.0, 16.0 Hz, 1 H).

¹³C NMR (125 MHz, CDCl3): δ = 166.5, 141.0, 136.5 (2 C), 135.6, 135.4, 130.2, 129.2, 128.6, 128.4, 128.3, 128.2, 127.7, 127.6, 127.5, 126.9, 56.3, 47.0, 33.9, 32.2.

LRMS (EI, 70 eV): m/z (%) = 351 (M+, 14), 351 (73), 350 (33), 349 (100), 258 (62), 245 (57), 215 (42), 202 (26), 91 (50).

HRMS (EI): m/z [M]+ calcd for C25H21NO: 351.1623; found: 351.1620.

Supporting Information for this article is available online at http://www.thieme-connect.com.accesdistant.sorbonne-universite.fr/ejournals/toc/synthesis.

Acknowledgment

The authors thank the Scientific Research Fund of Hunan Provincial Education Department (No. 08A037), Hunan Normal University (No. 080605), and National Natural Science Foundation of China (No. 20872112) for financial support.

7

The X-ray crystallographic data for compound 2a are summarized in Supporting Information.

7

The X-ray crystallographic data for compound 2a are summarized in Supporting Information.

   Permissions and Reprints All articles of this category

Scheme 1 Intramolecular cascade reactions

Figure 1 ORTEP diagram of the single-crystal X-ray structure of compound 2a

Scheme 2 A possible mechanism