HETEROCYCLES

Short Paper | Regular issue | Vol. 91, No. 8, 2015, pp. 1628-1636
Received, 21st April, 2015, Accepted, 11th June, 2015, Published online, 18th June, 2015.
DOI: 10.3987/COM-15-13231

■ Synthesis of Phenylselanylisochroman-1-ones through Highly Selective Selenolactonization of Styrene-Typed Carboxylic Acids

Enshan Zhou,* Xin Han, Yuanyuan Li, Chao Guo, and Chune Dong*

School of Pharmaceutical Sciences, Wuhan University, Hubei, Wuhan, 430071, China

Abstract

The novel synthesis of phenylselanylisochroman-1-ones was achieved by selenolactonization of styrene-typed carboxylic acids and phenylselenenyl chloride in the presence of 1,4-diazabicyclo[2.2.2]octane (DABCO). The reactions give excellent yields with high exo-selectivity.

Selenocyclization of unsaturated acids is one of efficient methods for the synthesis of series of oxygenated heterocycles.1 In particular, selenolactonization of alkenes attracts much attention in recent years since its widely application in total synthesis of bioactive compounds and natural products.2-4 Since Nicolaou et al first reported the selenolactonization reaction with unsaturated carboxylic acids in 1978, a number of selenocyclofunctionalization reactions have been reported.5-8 Although selenolactonization has been applied successfully to reactions involving allenoic acids,9 phenylbutenoic acids10 and other aliphatic acids,11 aromatic acids were less involved. In 1991, Narasimhan and coworkers reported the selenolactonisation of 2-((6,6-dimethyl-2-oxodihydro-2H-pyran-3(4H)-ylidene)methyl)benzoic acid with benzeneselenenyl chloride in the presence of pyridine to form the selenide in only 50% yield.12 However, there is still room for improvement regarding this type of selenolactonization reaction, for example, the existing reaction scope is still limited and the yield was poorer. Accordingly, the development of a practical, highly efficient reaction system for this type of selenolactonization is particularly attractive.
Recently, we have undertaken a program to investigate the halolactonization of styrene-typed carboxylic acids using C3-symmetric cinchonine-squaramide as organocatalyst, affording the corresponding chiral lactones, which can act as efficient non-nucleoside reverse transcriptase inhibitors.13 By analogy to previous work from this laboratory, selenolactonization of styrene-typed carboxylic acids has not been developed so far. Herein, we report the first examples of 1,4-diazabicyclo[2.2.2]octane (DABCO) catalyzed selenolactonization of styrene-typed carboxylic acids in the presence of phenylselenenyl chloride to provide phenylselanylisochroman-1-ones derivatives in excellent yields (Scheme 1).

This study was initiated with 2-vinylbenzoic acid 1a and phenylselenenyl chloride (PhSeCl) at room temperature in DCM. The desired product 2a was isolated in 55% yield (Table 1). Also, adjusting the DABCO loading demonstrated great influence on the activity of the reaction. The use of 5 mol% of DABCO gave the desired product 2a in only 35% yield (entry 2). When 15 mol% of DABCO was used, 2a was formed in 76% yield (entry 4). Screening of several solvents showed that DCM gave the best results. No reaction occurred when EtOAc and EtOH were used as solvent (entries 6, 7 and 8). Moreover, the amount of 1,4-diazabicyclo[2.2.2]octane (DABCO) had significant effect on the reaction. When 20 mol% of DABCO was applied, the product was formed in 87% yield (entry 5).

Encouraged by the results obtained with styrene carboxylic acid 1a, we investigated the selenolactonization of other unsaturated carboxylic acids with PhSeCl under these standard conditions. The results were summarized in Table 2. From Table 2, it was obvious that substituted benzoic acids can all be applied to afford series of phenylselanylisochroman-1-ones derivatives 2 in good to excellent yields (up to 94% yields) (entries 1-16). In all cases, a preference for the five-membered ring lactone 2 was observed, trace amount of six-membered ring lactone was detected. Interestingly, the substituted benzoic acids can all be tolerated in this reaction leading to the 5-exo selective products 2 in excellent yields. The substitutes at R2 position had no significant effect on the cyclization. For example, when 2-(1-(4-bromophenyl)vinyl)benzoic acid 1d was used in this reaction, the desired product 2d was formed in 94% yield (entry 6). Surprisingly, when methyl and propyl groups were substituted at R3 position, the yields were decreased. When the 1q and 1r were used, the corresponding products 2q and 2r were obtained in 75% and 60% yields, respectively (entries 17 and 18).

The product 2d was unambiguously confirmed by X-ray crystallography (Figure 1).

In conclusion, we present the new selenolactonization of styrene-typed carboxylic acids using phenylselenenyl chloride in the presence of DABCO. The resulting phenylselanylisochroman-1-one derivatives were formed in excellent yields under mild conditions. This methodology will serve as a convenient access to interesting phenyl selenoheterocyles.

EXPERIMENTAL
Analytical-grade solvents were purchased, and used as received. NMR spectra were measured at 400 MHz for 1H spectra and 100 MHz for 13C spectra and calibrated from residual solvent signal. Analytical thin-layer chromatography (TLC) was performed on silica gel aluminum sheets with F-254 indicator. Visualization was accomplished by UV light. Purification by chromatography was performed using 230-400 mesh SiO2 with compressed air as a source of positive pressure. Carboxylic acids 1 were prepared according to the literature procedure.14
Representative procedure for the selenolactonization of carboxylic acids
A solution of 2-vinylbenzoic acid 1a, phenylselenenyl chloride (1.1 equiv.), and DABCO (20 mol%) in DCM was stirred for 2 h at room temperature. Upon completion, the solvent was removed and the residue was purified by SiO2 column chromatography (petroleum ether/AcOEt = 6:1) to give 2a as white solid.
2a: white solid; mp 73-75 °C. 1H NMR (400 MHz, CDCl3) δ 7.90 (d, J = 7.1 Hz, 1H), 7.58 – 7.50 (m, 3H), 7.47 (dd, J = 7.6, 1.6 Hz, 2H), 7.23 (dt, J = 8.8, 4.8 Hz, 3H), 5.64 (t, J = 5.6 Hz, 1H), 3.45 (dd, J = 13.3, 5.0 Hz, 1H), 3.33 (dd, J = 13.3, 6.2 Hz, 1H). 13C NMR (100 MHz, CDCl3) δ 170.01, 148.57, 133.93, 133.64, 129.54, 129.29, 129.09, 127.77, 126.55, 125.66, 122.49, 79.11, 31.84. HRMS (ESI) calcd. for C15H13O2Se [M+H]+ 299.0140, found 299.0131.
2b: white solid; mp 77-79 °C. 1H NMR (400 MHz, CDCl3) δ 7.91 – 7.86 (m, 1H), 7.50 – 7.46 (m, 2H), 7.32 – 7.28 (m, 2H), 7.24 – 7.18 (m, 2H), 7.17 – 7.12 (m, 2H), 3.46 (d, J = 1.3 Hz, 2H), 1.77 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 169.50, 152.13, 133.80, 133.54, 130.10, 129.29, 129.00, 127.46, 126.63, 125.53, 121.22, 86.00, 38.98, 25.75. HRMS (ESI) calcd for C16H15O2Se [M+H]+ 313.0296, found 313.0290.
2c: white solid; mp 102-103 °C. 1H NMR (400 MHz, CDCl3) δ 7.95 – 7.90 (m, 1H), 7.54 – 7.45 (m, 4H), 7.37 – 7.31 (m, 4H), 7.28 – 7.25 (m, 2H), 7.20 (t, J = 7.3 Hz, 1H), 7.13 (t, J = 7.3 Hz, 2H), 3.88 – 3.80 (m, 2H). 13C NMR (100 MHz, CDCl3) δ 169.53, 150.79, 139.49, 133.84, 130.12, 129.47, 128.96, 128.83, 128.65, 128.12, 127.54, 126.74, 125.68, 125.29, 122.56, 88.43, 39.87. HRMS (ESI) calcd for C21H17O2Se [M+H]+ 375.0453, found 375.0444.
2d: white solid; mp 103-105 °C. 1H NMR (400 MHz, CDCl3) δ 7.94 – 7.90 (m, 1H), 7.51 – 7.45 (m, 4H), 7.34 (dd, J = 6.0, 1.8 Hz, 1H), 7.26 – 7.23 (m, 2H), 7.19 (dd, J = 7.9, 1.8 Hz, 1H), 7.12 (dd, J = 10.1, 4.5 Hz, 2H), 7.04 – 6.98 (m, 2H), 3.80 (d, J = 1.4 Hz, 2H). 13C NMR (100 MHz, CDCl3) δ 169.32, 162.67 (d, 1JC-F = 247.00 Hz), 150.56, 135.34, 135.30, 134.01, 133.84, 129.97, 129.65, 129.01, 127.63, 127.39 (d, 2JC-F = 8.00 Hz), 126.64, 125.75, 122.58, 115.72 (d, 3JC-F = 21.00 Hz), 88.05, 39.87. HRMS (ESI) calcd for C21H16FO2Se [M+H]+ 393.0358, found 393.0360.
2e: white solid; mp 105-107 °C. 1H NMR (400 MHz, CDCl3) δ 7.93 (dd, J = 6.2, 1.8 Hz, 1H), 7.52 – 7.42 (m, 4H), 7.34 – 7.20 (m, 6H), 7.13 (t, J = 7.3 Hz, 2H), 3.80 (t, J = 7.6 Hz, 2H). 13C NMR (100 MHz, CDCl3) δ 169.21, 150.40, 137.99, 134.69, 134.00, 133.89, 129.90, 129.69, 129.01, 128.95, 127.65, 126.81, 126.58, 125.84, 122.45, 87.92, 39.71.
2f: white solid; mp 104-106 °C. 1H NMR (400 MHz, CDCl3) δ 7.94 (dd, J = 6.2, 1.9 Hz, 1H), 7.55 – 7.50 (m, 2H), 7.48 – 7.44 (m, 2H), 7.36 – 7.30 (m, 3H), 7.26 (dd, J = 5.3, 3.3 Hz, 2H), 7.23 – 7.18 (m, 1H), 7.14 (dd, J = 10.1, 4.5 Hz, 2H), 3.80 (d, J = 1.8 Hz, 2H). 13C NMR (100 MHz, CDCl3) δ 169.56, 150.75, 138.33, 135.04, 134.35, 134.25, 130.25, 130.04, 129.36, 129.30, 128.01, 127.16, 126.93, 126.19, 122.80, 88.27, 40.06. HRMS (ESI) calcd for C21H16BrO2Se [M+H]+ 452.9558, found 452.9562.
2g: white solid; mp 100-102 °C. 1H NMR (400 MHz, CDCl3) δ 7.96 (d, J = 7.6 Hz, 1H), 7.72 – 7.53 (m, 4H), 7.37 (dd, J = 8.9, 6.5 Hz, 5H), 7.30 – 7.22 (m, 3H), 6.41 (s, 1H). 13C NMR (100 MHz, CDCl3) δ 163.19, 146.29, 137.79, 135.94, 134.66, 133.87, 130.46, 129.99, 129.90, 129.08, 129.02, 128.85, 128.67, 128.62, 128.40, 126.45, 125.80, 123.81, 84.18, 82.56, 46.14. HRMS (ESI) calcd for C21H16IO2Se [M+H]+ 500.9419, found 500.9414.
2h: white solid; mp 85-87 °C. 1H NMR (400 MHz, CDCl3) δ 7.91 (dd, J = 5.8, 1.6 Hz, 1H), 7.48 – 7.43 (m, 2H), 7.39 (d, J = 8.3 Hz, 2H), 7.34 – 7.22 (m, 4H), 7.15 (dd, J = 11.0, 4.3 Hz, 4H), 3.87 – 3.79 (m, 2H), 2.31 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 169.62, 150.98, 138.59, 136.52, 133.83, 133.79, 130.18, 129.49, 129.41, 128.95, 127.50, 126.72, 125.84, 125.60, 125.25, 125.11, 122.58, 88.48, 39.82, 21.09. HRMS (ESI) calcd for C22H19O2Se [M+H]+ 389.0609, found 389.0604.
2i: white solid; mp 88-90 °C. 1H NMR (400 MHz, CDCl3) δ 7.92 (dd, J = 6.1, 1.9 Hz, 1H), 7.52 – 7.46 (m, 2H), 7.43 – 7.39 (m, 2H), 7.33 (dd, J = 6.1, 1.7 Hz, 1H), 7.26 (dd, J = 5.3, 3.0 Hz, 3H), 7.22 – 7.18 (m, 1H), 7.13 (t, J = 7.3 Hz, 2H), 6.88 – 6.84 (m, 2H), 3.82 (d, J = 3.8 Hz, 2H), 3.78 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 169.52, 159.75, 150.95, 133.77, 133.73, 131.36, 130.18, 129.38, 128.93, 127.48, 126.84, 125.65, 122.61, 114.07, 113.98, 88.41, 55.34, 39.81. HRMS (ESI) calcd for C22H19O3Se [M+H]+ 405.0558, found 405.0553.
2j: white solid; mp 100-102 °C. 1H NMR (400 MHz, Acetone-d6) δ 7.82 – 7.62 (m, 6H), 7.77 – 7.65 (m, 5H), 7.51 (d, J = 7.9 Hz, 1H), 7.41 – 7.28 (m, 7H), 7.46 – 7.25 (m, 7H), 7.25 – 7.09 (m, 9H), 7.25 – 7.11 (m, 9H), 4.11 (d, J = 13.4 Hz, 2H), 4.11 (d, J = 13.4 Hz, 2H), 4.02 – 3.90 (m, 2H), 3.99 – 3.91 (m, 2H), 2.43 (s, 2H), 2.36 (d, J = 55.9 Hz, 5H), 2.29 (s, 3H). 13C NMR (100 MHz, Acetone-d6) δ 169.50, 163.42 (d, 1JC-F = 245.00 Hz), 152.28, 149.40, 146.42, 140.99, 137.50, 136.09, 134.07, 133.93, 131.65, 131.04, 130.88, 129.78, 129.77, 128.52 (d, 2JC-F = 8.00 Hz), 128.19, 128.08, 127.41, 125.83, 125.66, 124.80, 124.34, 123.59, 116.34 (d, 3JC-F = 22.00 Hz), 88.43, 88.26, 39.68, 39.49, 22.05, 21.16. HRMS (ESI) calcd for C22H18FO2Se [M+H]+ 407.0515, found 407.0505.
2k: white solid; mp 140-141 °C. 1H NMR (400 MHz, CDCl3) δ 7.86 (dd, J = 11.7, 4.9 Hz, 1H), 7.50 – 7.40 (m, 3H), 7.28 – 7.20 (m, 4H), 7.19 – 7.12 (m, 2H), 7.04 (ddd, J = 8.5, 5.3, 2.1 Hz, 2H), 3.83 – 3.73 (m, 2H). 13C NMR (100 MHz, CDCl3) δ 168.17, 163.91 (d, 1JC-F = 235.00 Hz), 152.02, 140.70, 133.85, 133.78, 130.36, 129.08, 129.00, 128.03, 127.25 (d, 2JC-F = 8.00 Hz), 126.83, 123.15, 115.91 (d, 3JC-F = 22.00 Hz), 87.60, 39.55. HRMS (ESI) calcd for C21H15ClFO2Se [M+H]+ 426.9969, found 426.9961.
2l: white solid; mp 135-137 °C. 1H NMR (400 MHz, CDCl3) δ 7.86 (dd, J = 11.6, 4.9 Hz, 1H), 7.40 (d, J = 8.7 Hz, 2H), 7.35 – 7.27 (m, 3H), 7.26 – 7.19 (m, 4H), 7.15 (dt, J = 12.2, 5.5 Hz, 3H), 3.81 – 3.74 (m, 2H). 13C NMR (100 MHz, CDCl3) δ 167.76, 148.41, 137.41, 136.05, 134.96, 133.93, 133.88, 133.81, 130.42, 129.13, 129.08, 129.02, 128.06, 127.78, 126.87, 126.73, 126.66, 125.57, 123.67, 123.08, 87.85, 39.67. HRMS (ESI) calcd for C21H15Cl2O2Se [M+H]+ 442.9673, found 442.9667.
2m: white solid; mp 92-94 °C. 1H NMR (400 MHz, CDCl3) δ 7.92 (d, J = 7.0 Hz, 1H), 7.72 (d, J = 7.6 Hz, 1H), 7.60 – 7.54 (m, 2H), 7.51 – 7.47 (m, 2H), 7.30 (ddd, J = 5.9, 3.4, 1.3 Hz, 2H), 7.25 – 7.22 (m, 1H), 5.59 (d, J = 2.9 Hz, 1H), 3.88 (tt, J = 7.2, 3.6 Hz, 1H), 1.31 (d, J = 7.2 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ 170.31, 147.20, 135.61, 134.79, 133.66, 129.50, 129.30, 129.23, 128.33, 128.16, 127.21, 125.66, 123.13, 82.76, 41.42, 16.43. HRMS (ESI) calcd for C16H15O2Se [M+H]+ 313.0296, found 313.0290.
2n: white solid; mp 104-105 °C. 1H NMR (400 MHz, CDCl3) δ 8.03 (d, J = 7.7 Hz, 1H), 7.53 – 7.50 (m, 2H), 7.46 (d, J = 7.6 Hz, 1H), 7.37 – 7.33 (m, 2H), 7.29 (d, J = 7.5 Hz, 2H), 7.20 (d, J = 7.6 Hz, 1H), 7.08 (d, J = 7.6 Hz, 1H), 7.00 (d, J = 7.3 Hz, 1H), 6.90 (s, 1H), 6.86 (d, J = 7.9 Hz, 1H), 5.80 (d, J = 1.8 Hz, 1H), 4.86 (d, J = 2.2 Hz, 1H), 2.23 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 163.69, 138.40, 138.13, 138.02, 136.62, 133.93, 130.06, 129.36, 129.11, 129.03, 128.47, 128.40, 128.24, 127.62, 126.62, 124.84, 122.89, 82.29, 43.78, 21.44. HRMS (ESI) calcd for C22H19O2Se [M+H]+ 389.0609, found 389.0608.
2o: white solid; mp 102-103 °C. 1H NMR (400 MHz, CDCl3) δ 8.02 (d, J = 7.7 Hz, 1H), 7.54 – 7.50 (m, 2H), 7.47 – 7.43 (m, 1H), 7.37 – 7.32 (m, 2H), 7.29 (s, 1H), 7.16 (ddd, J = 13.9, 7.3, 4.9 Hz, 2H), 6.99 (q, J = 8.3 Hz, 4H), 5.81 (d, J = 1.9 Hz, 1H), 4.84 (d, J = 2.2 Hz, 1H), 2.23 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 163.69, 138.09, 138.04, 136.59, 135.26, 133.90, 133.78, 130.04, 129.46, 129.36, 129.28, 129.08, 128.93, 128.38, 128.23, 127.62, 125.80, 125.23, 124.88, 82.22, 43.77, 21.03. HRMS (ESI) calcd for C22H19O2Se [M+H]+ 389.0609, found 389.0603.
2p: white solid; mp 107-109 °C. 1H NMR (400 MHz, CDCl3) δ 8.03 (d, J = 7.8 Hz, 1H), 7.53 – 7.45 (m, 3H), 7.38 – 7.33 (m, 2H), 7.28 (d, J = 7.6 Hz, 2H), 7.23 (d, J = 7.6 Hz, 1H), 7.00 (d, J = 8.7 Hz, 2H), 6.72 (d, J = 8.8 Hz, 2H), 5.79 (d, J = 2.4 Hz, 1H), 4.83 (d, J = 2.5 Hz, 1H), 3.72 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 163.70, 159.41, 138.21, 136.54, 133.95, 130.26, 130.09, 129.35, 129.06, 128.39, 128.28, 127.62, 127.38, 124.89, 113.93, 82.20, 55.23, 43.83. HRMS (ESI) calcd for C22H19O3Se [M+H]+ 405.0558, found 405.0550.
2q: white solid; mp 97-98 °C. 1H NMR (400 MHz, CDCl3) δ 7.89 (dd, J = 6.0, 2.0 Hz, 1H), 7.54 – 7.48 (m, 2H), 7.43 (dd, J = 6.0, 1.9 Hz, 1H), 7.40 – 7.35 (m, 2H), 7.27 – 7.24 (m, 1H), 7.23 – 7.16 (m, 2H), 3.71 (q, J = 7.2 Hz, 1H), 1.76 (s, 3H), 1.44 (d, J = 7.2 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ 169.85, 152.30, 134.79, 133.72, 129.64, 129.30, 129.06, 127.88, 126.66, 125.55, 121.73, 89.17, 48.12, 25.04, 17.88. HRMS (ESI) calcd for C17H17O2Se [M+H]+ 327.0453, found 327.0451.
2r: white solid; mp 112-113 °C. 1H NMR (400 MHz, CDCl3) δ 7.91 (d, J = 7.6 Hz, 1H), 7.47 – 7.39 (m, 3H), 7.32 (dd, J = 15.6, 8.5 Hz, 2H), 7.26 – 7.22 (m, 2H), 7.19 (t, J = 7.3 Hz, 1H), 7.06 (t, J = 7.6 Hz, 2H), 7.02 – 6.95 (m, 2H), 3.83 (dd, J = 10.9, 2.1 Hz, 1H), 1.94 – 1.84 (m, 1H), 1.57 – 1.38 (m, 3H), 0.87 (t, J = 7.2 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ 169.79, 151.09, 138.27, 134.54, 133.50, 129.32, 128.82, 128.75, 127.57, 126.51, 125.73, 122.57, 91.59, 57.34, 33.27, 21.51, 13.64. HRMS (ESI) calcd for C24H22BrO2Se [M+H]+ 495.0027, found 495.0014.

ACKNOWLEDGEMENTS
We are grateful to the Fundamental Research Funds for the Central Universities (2042014kf0248) for support of this research.

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