Direct cyclization of 1,3-diaryl propargylic alcohols with β-dicarbonyl compounds by palladium-boric acid dual-catalyst system

Tetrahedron 72 (2016) 5633e5639

Contents lists available at ScienceDirect

Tetrahedron journal homepage: www.elsevier.com/locate/tet

Direct cyclization of 1,3-diaryl propargylic alcohols with b-dicarbonyl compounds by palladium-boric acid dual-catalyst system Masahiro Yoshida a, *, Shoko Ohno b, Sayaka Eguchi a, Tomotaka Mizuguchi b, Kenji Matsumoto a, Kosuke Namba b a b

Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Nishihama, Yamashiro-cho, Tokushima, 770-8514, Japan Graduate School of Pharmaceutical Sciences, Tokushima University, 1-78-1 Sho-machi, Tokushima, 770-8505, Japan

a r t i c l e i n f o

a b s t r a c t

Article history: Received 21 June 2016 Received in revised form 21 July 2016 Accepted 25 July 2016 Available online 26 July 2016

Palladium and boric acid-catalyzed cyclization of underivatized 1,3-diaryl propargylic alcohols with 1,3cyclohexanediones has been developed. Boric acid plays a role for the efficient activation of the propargylic alcohols. Various substituted tetrahydrobenzofuranones were obtained in moderate to good yields. Reactions using 4-hydroxy-2-pyrones as the nucleophile also proceeded to afford the substituted dihydrofuropyranones. Ó 2016 Elsevier Ltd. All rights reserved.

Keywords: Cyclization b-Dicarbonyl compounds Lewis acids Palladium Propargyl alcohols

1. Introduction Propargylic compounds having an elimination group at the propargylic position are known as useful substrates in the palladium-catalyzed reactions.1 For example, palladium-catalyzed cyclization of propargylic compounds with bis-nucleophiles, which contain two nucleophilic parts within the molecules, has been reported (Eq. 1).2 In this reaction, p-propargylpalladium intermediate is initially formed, which is subjected to consecutive nucleophilic attacks by the bis-nucleophiles to give the cyclized product. The reaction often employs activated propargylic alcohol derivatives such as propargylic esters, carbonates and halides, and to the best of our knowledge, no examples have been reported about the palladium-catalyzed reactions of underivatized propargylic alcohols with soft nucleophiles.3 On the other hand, much attention has been paid to the direct use of allylic alcohols for the Tsuji-Trost type reactions, in which an activation of the allylic alcohols4 by the addition of activator such as Lewis acids,5 Brønsted acids,6 ligands and solvents7 is one of the useful methodologies for the smooth generation of p-allylpalladium intermediates (Eq. 2). We expected that similar activation effect could occur in the

* Corresponding author. E-mail address: [email protected] (M. Yoshida). http://dx.doi.org/10.1016/j.tet.2016.07.055 0040-4020/Ó 2016 Elsevier Ltd. All rights reserved.

formation of p-propargylpalladium species by the reaction of propargylic alcohols with palladium. Thus, direct cyclization of propargylic alcohols with bis-nucleophiles could smoothly proceed by the addition of activator (Eq. 3). Herein, we describe syntheses of substituted tetrahydrobenzofuranones and dihydrofuropyranones by the direct cyclization of 1,3-diaryl propargylic alcohols with 1,3cyclohexanediones and 4-hydroxy-2-pyrones. In this reaction, palladium and boric acid dual-catalyst system plays a role for the efficient activation of the propargylic alcohols.

ð1Þ

5634

M. Yoshida et al. / Tetrahedron 72 (2016) 5633e5639

ð2Þ

ð3Þ

2. Results and discussion The initial attempts were started using 1,3-diphenylpropargyl alcohol (1a) and 1,3-cyclohexanedione (2a) using various acids as an activator (Table 1). When 1a and 2a were treated with 10 mol % Pd(PPh3)4 and 1 equiv B(OH)3 as an activator in dioxane at 100  C for 3 h, the reaction successfully proceeded to afford the tetrahydrobenzofuranone 3aa in 45% yield (entry 1). Decomposition of the substrates was observed in the presence of BF3$OEt2 (entry 2), and the cyclized product 3aa was produced in 10% yield when Sc(OTf)3 was employed (entry 3). The reactions using alkylboronic acids such as MeB(OH)2, EtB(OH)2 and BuB(OH)2 resulted in the production of 3aa in low yields, respectively (entries 4e6). The use of B(OMe)3 or B(OTMS)3 were also not effective (entries 7 and 8), but the yield was increased to 52% when B(OiPr)3 was employed (entry 9). On the other hand, when Brønsted acid such as benzoic acid was employed as an activator,6i the cyclized product 3aa was not obtained (entry 10). From these results, it was found that B(OH)3 or B(OiPr)3 is suitable for the activation of propargylic alcohols.

Table 2 Attempts using various phosphine ligands

Entry

Ligand

Lewis acid

Yield (%)

1 2 3 4 5 6 7 8

DPPE DPPP DPPB DPPPent DPPF DPEPhos BINAP BINAP

B(OiPr)3 B(OiPr)3 B(OiPr)3 B(OiPr)3 B(OiPr)3 B(OiPr)3 B(OiPr)3 B(OH)3

34 67 71 55 48 32 76 80

Table 3 Examinations using various palladium sources

Entry

Palladium

Amount of B(OH)3

Yield (%)

1 2 3 4 5

Pd(OCOCF3)2 PdCl2(MeCN)2 Pd(OAc)2 Pd(OAc)2 Pd(OAc)2

1 equiv 1 equiv 1 equiv 0.2 equiv None

46 No reaction 87 84 20

Table 1 Initial attempts using various activators

Entry

Activator

Time (h)

Yield (%)

1 2 3 4 5 6 7 8 9 10

B(OH)3 BF3$OEt2 Sc(OTf)3 MeB(OH)2 EtB(OH)2 BuB(OH)2 B(OMe)3 B(OTMS)3 B(OiPr)3 PhCO2H

3 1 5 2.5 3.5 5.5 6 9 3 3

45 Decomp 10 12 31 19 12 30 52 Decomp

We next examined the effect of phosphine ligands in the reaction of 1a with 2a (Table 2). When DPPE was subjected to the reaction in the presence of 5 mol % Pd2(dba)3$CHCl3 and 1 equiv B(OiPr)3, the cyclized product 3aa was produced in 34% yield (entry 1). The yields were increased to 67% and 71% by the use of DPPP and DPPB, respectively (entries 2 and 3). The reactions using DPPPent, DPPF and DPEPhos also proceeded to afford 3aa in moderate yields (entries 4e6). A better result was obtained to give 3aa in 76% yield in the case of BINAP (entry 7),8 and the yield was increased to 80% when B(OH)3 was employed instead of B(OiPr)3 (entry 8). Table 3 summarized the examination using various palladium sources in combination with 20 mol % BINAP and 1 equiv B(OH)3. The reaction using 10 mol % Pd(OCOCF3)2 gave the product 3aa in

46% yield (entry 1), but no reaction proceeded in the case of PdCl2(MeCN)2 (entry 2). The yield was increased to 87% when the reaction was conducted with 10 mol % Pd(OAc)2 (entry 3), and the similar reactivity was observed even in the presence of 20 mol % B(OH)3 (entry 4). On the other hand, the yield of 3aa was decreased to 20% in the absence of B(OH)3 (entry 5). This result indicates that B(OH)3 is necessary as the catalyst to promote the reaction. Having identified a useful set of reaction conditions, we next carried out a study on the substrate scope using various 1,3-diarylsubstituted propargylic alcohols 1be1e with 2a (Table 4).9 When di-p-tolyl-substituted propargylic alcohol 1b was subjected to the reaction, the corresponding tetrahydrobenzofuranone 3ba was obtained in 81% yield (entry 1). The substrates 1c and 1d having oand p-fluorophenyl groups successfully reacted with 2a to produce the products 3ca and 3da, respectively (entries 2 and 3). The reaction of di-p-chlorophenyl-substituted substrate 1e also proceeded to give the cyclized product 3ea in 84% yield (entry 4). The structure of 3ea, including the geometry of olefin, was confirmed by X-ray crystallographic analysis (Fig. 1).10 The reactions using substituted 1,3-cyclohexanediones 2be2e are summarized in Table 5. The reaction of 5-methyl-1,3cyclohexanedione (2b) with 1a proceeded to afford the tetrahydrobenzofuranones 3ab in 82% yield as a 1:1 diastereomixture (entry 1). When the substrates 2c and 2d having a phenyl and dimethyl group were subjected to the reactions, the corresponding products 3ac and 3ad were produced in 80% and 77% yield, respectively (entries 2 and 3). 4,4-Dimethylcyclohexane-1,3-dione (2e) was regioselectively transformed into the cyclized product 3ae in 53% yield based on recovered starting material (entry 4).

M. Yoshida et al. / Tetrahedron 72 (2016) 5633e5639 Table 4 Reactions using 1,3-diaryl-substituted propargyl alcohols 1be1e

Table 5 Reactions using substituted 1,3-cyclohexanediones 2be2ea Entry

Entry

Substrate 1 Ar

1

4-Methylphenyl (1b)

2

3

Product 3

2-Fluorophenyl (1c)

4-Fluorophenyl (1d)

5635

Substrate 2

Product 3

Yield (%)

1b

82 (dr 1:1)

2

80 (dr 1:1)

3

77

4b

53 (brsm)

Yield (%)

81

85

62 a The reactions were carried out using 1a and 2 (1.2 equiv) in the presence of 10 mol % Pd(OAc)2, 20 mol % BINAP and 20 mol % B(OH)3 in dioxane at 100  C for 2e4 h. b 3 equiv of 2e was used.

4

4-Chrolophenyl (1e)

Fig. 1. ORTEP drawing of 3ea.

84

A plausible mechanism for the cyclization process is shown in Scheme 1. The propargylic alcohol 1 is initially activated by the coordination of boric acid to form the reactive complex 4, which undergoes dehydroxylation by reacting with the palladium to generate the p-propargylpalladium 5.11 The intermediate is then

Scheme 1. Proposed reaction mechanism.

5636

M. Yoshida et al. / Tetrahedron 72 (2016) 5633e5639

Table 6 Reactions using substituted 4-hydroxy-2-pyrones 2fe2ka Entry

1

Substrate 2

Product 3

Yield (%)

62

Pd(OAc)2, 20 mol % BINAP and 20 mol % B(OH)3 in dioxane at 100  C, the dihydrofuropyranone 3fa was obtained in 62% yield (entry 1). The substrates 2ge2i having a methyl, a heptyl and an allyl group at the 5-position, successfully reacted to produce the corresponding products 3ga, 3ha and 3ia in good yields, respectively (entries 2e4). The reactions using p-fluorobenzyl- and propargyl-substituted substrates 2j and 2k also proceeded to afford the corresponding products 3ja and 3ka in 48% and 72% yields, respectively (entries 5 and 6). 3. Conclusion

2

92

3

91

In summary, the studies described above have resulted in the syntheses of substituted tetrahydrobenzofuranones and dihydrofuropyranones by the palladium and boric acid-catalyzed reaction of underivatized 1,3-diaryl propargylic alcohols with 1,3cyclohexanediones and 4-hydroxy-2-pyrones. Palladium and boric acid dual-catalyst system is important for the efficient activation of the propargylic alcohols. This methodology would provide a new protocol for the convenient synthesis of tetrahydrobenzofuranones and dihydrofuropyranones. 4. Experimental 4.1. General

4

72

5

48

All nonaqueous reactions were carried out under a positive atmosphere of argon in dried glassware unless otherwise indicated. Materials were obtained from commercial suppliers and used without further purification except when otherwise noted. Solvents were dried and distilled according to standard protocol. Propargylic alcohols 1ae1e and 4-hydroxy-2-pyrones 2fe2k were prepared according to the procedures described in the literature.2i,13 4.2. General procedure for the reaction of propargyl alcohols 1 with bLdicarbonyl compounds 2

6

72

a The reactions were carried out using 1a and 2 (1.2 equiv) in the presence of 10 mol % Pd(OAc)2, 20 mol % BINAP and 20 mol % B(OH)3 in dioxane at 100  C for 2e4 h.

subjected to the nucleophilic attack of the enolate 6, derived from cyclohexanedione 2 and tetrahydroxyborate, to afford the p-allylpalladium syn-7 and anti-7. There would be p-s-p equilibrium between syn-7 and anti-7, and intramolecular attack of the hydroxy anion occurs from anti-7 because of the absence of steric repulsion to produce the cyclized product 3. We next turned our attention to the use of 4-hydroxy-2pyrones 2fe2k as a bis-nucleophile (Table 6).12 When 4hydroxy-6-methyl-2H-pyran-2-one (2f) and propargylic alcohol 1a were subjected to the reaction in the presence of 10 mol %

Synthesis of 3aa (Table 3, entry 4). A stirred solution of Pd(OAc)2 (5.8 mg, 26 mmol) and BINAP (32 mg, 51 mmol) in dioxane (1.0 mL) was heated to 100  C, and stirring was continued for 5 min. After the resulting solution was cooled to rt, propargylic alcohol 1a (54 mg, 257 mmol), 1,3-cyclohexanedione (2a) (35 mg, 308 mmol) and boric acid (3.2 mg, 51 mmol) in dioxane (1.6 mL) were added. The reaction mixture was then allowed to heat to 100  C, and stirring was continued for 2 h. After filtration of the reaction mixture using small amount of silica gel followed by concentration, the residue was chromatographed on silica gel with hexaneeAcOEt (80:20 v/v) as eluent to give 3aa (66 mg, 84% yield). 4.3. (Z)-3-Benzylidene-2-phenyl-3,5,6,7-tetrahydrobenzofuran4(2H)-one (3aa) Yield 84%; colorless plates (AcOEt, mp 179.7e180.9  C); IR (KBr) 2951, 1651, 1631 cm1; 1H NMR (400 MHz, CDCl3) d 2.10 (2H, tt, J¼6.4 and 6.4 Hz), 2.50 (2H, t, J¼6.4 Hz), 2.56 (2H, dt, J¼1.6 and 6.4 Hz), 6.56 (1H, d, J¼2.8 Hz), 7.00e7.08 (3H, m), 7.09e7.14 (2H, m), 7.29e7.33 (3H, m), 7.38e7.42 (2H, m), 7.67 (1H, d, J¼2.8 Hz); 13C NMR (100 MHz, CDCl3) d 21.3 (CH2), 24.7 (CH2), 37.7 (CH2), 89.0 (CH), 115.4 (Cq), 120.2 (CH), 126.1 (CH), 128.0 (CH), 128.1 (CH), 128.2 (CH), 128.8 (CH), 129.2 (CH), 135.0 (Cq), 136.1 (Cq), 136.7 (Cq), 180.5 (Cq), 194.2 (Cq); HRMS (ESI) m/z calcd for C21H18NaO2 [MþNa]þ 325.1204, found 325.1208.

M. Yoshida et al. / Tetrahedron 72 (2016) 5633e5639

4.4. (Z)-3-(4-Methylbenzylidene)-2-(p-tolyl)-3,5,6,7tetrahydrobenzofuran-4(2H)-one (3ba) Yield 81%; colorless plates (AcOEtehexane, mp 145.8e151.0  C); IR (KBr) 2948, 1653, 1599 cm1; 1H NMR (400 MHz, CDCl3) d 2.08 (2H, quint, J¼6.4 Hz), 2.22 (3H, s), 2.31 (3H, s), 2.48 (2H, t, J¼6.4 Hz), 2.54 (2H, t, J¼6.4 Hz), 6.51 (1H, d, J¼2.8 Hz), 6.94 (2H, d, J¼8.4 Hz), 6.98 (2H, d, J¼8.4 Hz), 7.13 (2H, d, J¼8.0 Hz), 7.31 (2H, d, J¼8.0 Hz) 7.63 (1H, d, J¼2.8 Hz); 13C NMR (100 MHz, CDCl3) d 21.0 (CH3), 21.2 (CH3), 21.3 (CH2), 24.8 (CH2), 37.7 (CH2), 88.9 (CH), 115.4 (Cq), 120.1 (CH), 128.0 (CH), 128.2 (CH), 128.8 (CH), 129.6 (CH), 133.3 (Cq), 133.9 (Cq2), 135.9 (Cq), 139.1 (Cq), 180.2 (Cq), 194.3 (Cq); HRMS (ESI) m/z calcd for C23H22NaO2 [MþNa]þ 353.1517, found 353.1518. 4.5. (Z)-3-(2-Fluorobenzylidene)-2-(2-fluorophenyl)-3,5,6,7tetrahydrobenzofuran-4(2H)-one (3ca) Yield 85%; colorless needles (AcOEtehexane, mp 133.5e135.8  C); IR (KBr) 2951, 1659, 1600 cm1; 1H NMR (400 MHz, CDCl3) d 2.13 (2H, quint, J¼6.4 Hz), 2.52 (2H, t, J¼6.4 Hz), 2.60 (2H, q, 6.4 Hz), 6.79 (1H, d, J¼2.8 Hz), 6.80e6.87 (2H, m), 6.90e7.02 (4H, m), 7.12e7.23 (2H, m), 7.60 (1H, d, J¼2.8 Hz); 13C NMR (100 MHz, CDCl3) d 21.3 (CH2), 24.7 (CH2), 37.6 (CH2), 82.8 (CH, dd, J¼5.8 and 3.3 Hz), 112.2 (CH, d, J¼3.3 Hz), 115.08 (Cq), 115.13 (CH, d, J¼22.3 Hz), 115.3 (CH, d, J¼21.5 Hz), 123.1 (Cq, d, J¼14.0 Hz), 123.4 (CH, d, J¼3.3 Hz), 124.2 (CH, d, J¼3.3 Hz), 124.6 (Cq, d, J¼14.0 Hz), 128.0 (CH, d, J¼8.3 Hz), 128.8 (CH, d, J¼4.1 Hz), 129.2 (CH, d, J¼3.3 Hz), 131.0 (CH, d, J¼8.3 Hz), 137.7 (Cq), 159.5 (Cq, d, J¼247 Hz), 161.1 (Cq, d, J¼249 Hz), 181.7 (Cq), 194.0 (Cq); HRMS (ESI) m/z calcd for C21H16F2NaO2 [MþNa]þ 361.1016, found 361.1012. 4.6. (Z)-3-(4-Fluorobenzylidene)-2-(4-fluorophenyl)-3,5,6,7tetrahydrobenzofuran-4(2H)-one (3da) Yield 62%; colorless oil; IR (neat) 2951, 1654, 1605, 1508 cm1; H NMR (400 MHz, CDCl3) d 2.11 (2H, tt, J¼6.4 and 6.4 Hz), 2.50 (2H, t, J¼6.4 Hz), 2.57 (2H, dt, J¼3.2 and 6.4 Hz), 6.50 (1H, d, J¼2.8 Hz), 6.81 (2H, t, J¼8.4 Hz), 6.95e7.15 (4H, m), 7.35 (2H, dd, J¼5.2 and 8.4 Hz), 7.62 (1H, d, J¼2.8 Hz); 13C NMR (100 MHz, CDCl3) d 21.3 (CH2), 24.7 (CH2), 37.7 (CH2), 89.0 (CH), 115.0 (CH, d, J¼21.5 Hz), 115.8 (CH, d, J¼21.4 Hz), 119.2 (CH), 129.7 (CH, d, J¼8.3 Hz), 130.1 (CH, d, J¼9.1 Hz), 131.8 (Cq, d, J¼3.3 Hz), 132.8 (Cq, d, J¼3.3 Hz), 134.86 (Cq), 134.87 (Cq), 160.9 (Cq, d, J¼192 Hz), 163.3 (Cq, d, J¼193 Hz), 180.5 (Cq), 194.2 (Cq); HRMS (ESI) m/z calcd for C21H17F2O2 [MþH]þ 339.1197, found 339.1191. 1

4.7. (Z)-3-(4-Chlorobenzylidene)-2-(4-chlorophenyl)-3,5,6,7tetrahydrobenzofuran-4(2H)-one (3ea) Yield 84%; colorless plates (acetone, mp 168.0e169.7  C); IR (KBr) 2949, 1654, 1603 cm1; 1H NMR (300 MHz, CDCl3) d 2.10 (2H, tt, J¼6.6 and 6.6 Hz), 2.50 (2H, t, J¼6.6 Hz), 2.56 (2H, dt, J¼2.4 and 6.4 Hz), 6.50 (1H, d, J¼3.0 Hz), 6.96 (2H, d, J¼8.4 Hz), 7.10 (2H, d, J¼8.4 Hz), 7.28e7.32 (4H, m), 7.61 (1H, d, J¼3.0 Hz); 13C NMR (100 MHz, CDCl3) d 21.3 (CH2), 24.7 (CH2), 37.6 (CH2), 87.9 (CH), 115.2 (Cq), 119.1 (CH), 128.3 (CH), 129.2 (CH), 129.3 (CH), 129.5 (CH), 132.0 (Cq), 134.1 (Cq), 135.0 (Cq), 135.3 (Cq), 135.4 (Cq), 180.7 (Cq), 194.2 (Cq); HRMS (ESI) m/z calcd for C21H17Cl2O2 [MþH]þ 371.0606, found 371.0608. X-ray crystallographic analysis of 3ea.10 A colorless block crystal having approximate dimensions of 0.600.400.30 mm was mounted on a glass fiber. All measurements were made on a Rigaku RAXIS RAPID imaging plate area detector with graphite monochromated Mo-Ka radiation. The structure was solved by direct methods (SIR97) and expanded using

5637

Fourier techniques (DIRDIF99). The non-hydrogen atoms were refined anisotropically. Hydrogen atoms were refined using the riding model. The final cycle of full-matrix least-squares refinement on F was based on 16691 observed reflections (I>0.00s(I)) and 243 variable parameters, and converged (largest parameter shift was 0.50 times its esd) with unweighted and weighted agreement factors of R¼0.065 and Rw¼0.180. Crystal data for 3ea: C21H16O2Cl2, M¼371.26, monoclinic, space group P21/c (#14), a¼12.0101(5)  A, b¼9.0739(3)  A, c¼17.4689(7)  A, b¼110.131(1) , V¼1787.4(1)  A3 , Z¼4, Dc¼1.380 g/cm3, F(000)¼768, m(MoKa)¼3.74 cm1. 4.8. (2R*,6R*)- and (2R*,6S*)-3-(Z)-Benzylidene-6-methyl-2phenyl-3,5,6,7-tetrahydrobenzofuran-4(2H)-one (syn-3ab and anti-3ab) Yield 82%; colorless needles (AcOEtehexane, mp 146.6e147.2  C) 1:1 mixture of diastereomers; IR (KBr) 2953, 1652, 1602 cm1; 1H NMR (400 MHz, CDCl3) for 1:1 mixture of diastereomers: d 1.13 (1.5H, s), 1.15 (1.5H, s), 2.20e2.32 (2H, m), 2.32e2.44 (1H, m), 2.54 (1H, dt, J¼16.4 and 3.2 Hz), 2.61 (1H, dt, J¼16.4 and 3.2 Hz), 6.57 (1H, d, J¼2.8 Hz), 7.00e7.08 (3H, m), 7.08e7.14 (2H, m), 7.29e7.33 (3H, m), 7.37e7.42 (2H, m), 7.64 (0.5H, d, J¼2.8 Hz), 7.66 (0.5H, d, J¼2.8 Hz); 13C NMR (100 MHz, CDCl3) for mixture of diastereomers: d 20.88 (CH3), 20.91 (CH3), 29.3 (CH), 29.5 (CH), 32.6 (CH2), 32.7 (CH2), 46.20(CH2), 46.22 (CH2), 89.35 (CH), 89.38 (CH), 115.0 (Cq), 115.1 (Cq), 120.0 (CH), 120.2 (CH), 126.1 (CH2), 128.01 (CH2), 128.08 (CH), 128.15 (CH), 128.20 (CH), 128.22 (CH), 128.8 (CH2), 129.2 (CH2), 135.0 (Cq2), 136.1 (Cq2), 136.7 (Cq2), 180.2 (Cq2), 193.8 (Cq2); HRMS (ESI) m/z calcd for C22H21O2 [MþH]þ 317.1542, found 317.1546. 4.9. (2R*,6R*)- and (2R*,6S*)-3-(Z)-Benzylidene-2,6-diphenyl3,5,6,7-tetrahydrobenzofuran-4(2H)-one (syn-3ac and anti3ac) Yield 80%; colorless needles (acetoneeAcOEt, mp 171.0e174.1  C); mixture of diastereomers; IR (KBr) 3029, 1654, 1605 cm1; 1H NMR (400 MHz, CDCl3) for 1:1 mixture of diastereomers: d 2.74e2.84 (4H, m), 3.94 (1H, tt, J¼8.0 and 8.0 Hz), 6.62 (1H, d, J¼2.8 Hz), 7.01e7.09 (3H, m), 7.09e7.16 (2H, m), 7.24e7.30 (3H, m), 7.30e7.38 (5H, m), 7.38e7.42 (1H, m), 7.42e7.46 (1H, m), 7.68 (0.5H, d, J¼2.8 Hz), 7.71 (0.5H, d, J¼2.8 Hz); 13C NMR (100 MHz, CDCl3) for mixture of diastereomers: d 32.2 (CH2), 32.3 (CH2), 39.8 (CH), 40.1 (CH), 45.0 (CH2), 45.3 (CH2), 89.7 (CH), 89.8 (CH), 115.4(Cq), 115.5 (Cq), 120.5 (CH), 120.8 (CH), 126.32 (CH), 126.33 (CH), 126.69 (CH), 126.72 (CH), 127.2 (CH), 128.1 (CH), 128.2 (CH), 128.28 (CH), 128.31 (CH), 128.4 (CH), 128.85 (CH), 128.88 (CH), 128.91 (CH), 128.93 (CH), 129.31 (CH), 129.32 (CH), 134.67 (Cq), 134.73 (Cq), 136.06 (Cq), 136.07 (Cq), 136.63 (Cq), 136.66 (Cq), 142.2 (Cq), 142.3 (Cq), 179.6 (Cq2), 192.75 (Cq), 192.80 (Cq); HRMS (ESI) m/z calcd for C27H22NaO2 [MþNa]þ 401.1517, found 401.1525. 4.10. (Z)-3-Benzylidene-6,6-dimethyl-2-phenyl-3,5,6,7tetrahydrobenzofuran-4(2H)-one (3ad) Yield 77%; colorless needles (AcOEtehexane, mp 126.7e129.6  C); IR (KBr) 2958, 1654, 1606 cm1; 1H NMR (400 MHz, CDCl3) d 1.13 (3H, s), 1.16 (3H, s), 2.39 (2H, s), 2.43 (2H, s), 6.58 (1H, d, J¼2.8 Hz), 7.00e7.15 (5H, m), 7.28e7.34 (3H, m), 7.38e7.43 (2H, m), 7.66 (1H, d, J¼2.8 Hz); 13C NMR (100 MHz, CDCl3) d 28.5 (CH3), 28.6 (CH3), 34.0 (Cq), 38.5 (CH2), 52.1 (CH2), 89.4 (CH), 114.2 (Cq), 120.0 (CH), 126.1 (CH), 128.0 (CH), 128.1 (CH), 128.2 (CH), 128.8 (CH), 129.2 (CH), 135.0 (Cq), 136.3 (Cq), 136.7 (Cq), 179.6 (Cq), 193.5 (Cq); HRMS (ESI) m/z calcd for C23H22O2Na [MþNa]þ 353.1517, found 353.1517.

5638

M. Yoshida et al. / Tetrahedron 72 (2016) 5633e5639

4.11. (Z)-3-Benzylidene-7,7-dimethyl-2-phenyl-3,5,6,7tetrahydrobenzofuran-4(2H)-one (3ae) Yield 25% (53% yield based on recovered starting material); colorless plates (AcOEt, mp 138.3e144.0  C); IR (KBr) 2965, 2928, 1655, 1589 cm1; 1H NMR (400 MHz, CDCl3) d 1.17 (3H, s), 1.29 (3H, s), 1.85e1.98 (2H, m), 2.56 (2H, t, J¼6.4 Hz), 6.51 (1H, d, J¼2.8 Hz), 7.00e7.08 (3H, m), 7.09e7.15 (2H, m), 7.27e7.30 (3H, m), 7.32e7.36 (2H, m), 7.61 (1H, d, J¼2.8 Hz); 13C NMR (100 MHz, CDCl3) d 24.9 (CH32), 33.4 (Cq), 35.5 (CH2), 36.6 (CH2), 88.7 (CH), 113.1 (Cq), 120.4 (CH), 126.2 (CH), 128.00 (CH), 128.03 (CH), 128.2 (CH), 128.7 (CH), 129.0 (CH), 136.2 (Cq), 136.6 (Cq), 136.9 (Cq), 186.3 (Cq), 194.1 (Cq); HRMS (ESI) m/z calcd for C23H22NaO2 [MþNa]þ 353.1517, found 353.1510. The stereochemistry of 3ae was determined unambiguously by HMBC correlation. 4.12. (Z)-3-Benzylidene-6-methyl-2-phenyl-2,3-dihydro-4Hfuro[3,2-c]pyran-4-one (3fa) Yield 62%; colorless plates (acetoneehexane, mp 166.9e169.4  C); IR (KBr) 3030, 1724, 1626, 1569 cm1; 1H NMR (400 MHz, CDCl3) d 2.30 (3H, s), 5.99 (1H, s), 6.72 (1H, d, J¼2.8 Hz), 7.03e7.17 (5H, m), 7.30e7.34 (3H, m), 7.38e7.46 (2H, m), 7.49 (1H, d, J¼2.8 Hz); 13C NMR (100 MHz, CDCl3) d 20.6 (CH3), 91.1 (CH), 96.1 (CH), 103.5 (Cq), 121.1 (CH), 126.7 (CH), 128.2 (CH2), 128.4 (CH), 129.0 (CH), 129.5 (CH), 132.9 (Cq), 135.7 (Cq), 136.0 (Cq), 159.5 (Cq), 165.9 (Cq), 171.6 (Cq); HRMS (ESI) m/z calcd for C21H16NaO3 [MþNa]þ 339.0997, found 339.1005. 4.13. (Z)-3-Benzylidene-6,7-dimethyl-2-phenyl-2,3-dihydro4H-furo[3,2-c]pyran-4-one (3ga) Yield 92%; pale yellow prisms (AcOEtehexane, mp 217.2e223.0  C); IR (ATR) 1699, 1556, 1495, 1445, 1369, 1241, 1109, 1006, 912, 861, 750 cm1; 1H NMR (500 MHz, CDCl3) d 1.91 (3H, s), 2.27 (3H, s), 6.72 (1H, d, J¼2.5 Hz), 7.03e7.07 (1H, m), 7.08e7.16 (4H, m), 7.30e7.33 (3H, m), 7.41e7.45 (2H, m), 7.50 (1H, d, J¼2.5 Hz); 13C NMR (125 MHz, CDCl3) d 9.1 (CH3), 17.5 (CH3), 89.9 (CH), 103.4 (Cq), 103.7 (Cq), 120.9 (CH), 126.5 (CH), 128.2 (CH), 128.3 (CH), 128.4 (CH), 128.9 (CH), 129.4 (CH), 133.6 (Cq), 135.7 (Cq), 136.1 (Cq), 159.5 (Cq), 161.6 (Cq), 171.8 (Cq); HRMS (ESI) m/z calcd for C22H18O3Na [MþNa]þ 353.1154, found 353.1154. 4.14. (Z)-3-Benzylidene-7-heptyl-6-methyl-2-phenyl-2,3dihydro-4H-furo[3,2-c]pyran-4-one (3ha) Yield 91%; colorless prisms (AcOEtehexane, mp 109.8e111.1  C); IR (ATR) 2923, 1713, 1557, 1444, 1235, 907, 750 cm1; 1H NMR (500 MHz, CDCl3) d 0.85 (3H, t, J¼6.5 Hz), 1.12e1.26 (8H, m), 1.31e1.46 (2H, m), 2.27 (3H, s), 2.25e2.37 (2H, m), 6.71 (1H, s), 7.04e7.08 (1H, m), 7.09e7.16 (4H, m), 7.28e7.33 (3H, m), 7.39e7.43 (2H, m), 7.49 (1H, s); 13C NMR (125 MHz, CDCl3) d 14.1 (CH3), 17.3 (CH3), 22.6 (CH2), 24.1 (CH2), 28.9 (CH2), 28.9 (CH2), 29.0 (CH2), 31.6 (CH2), 89.7 (CH), 103.6 (Cq), 108.7 (Cq), 120.9 (CH), 126.5 (CH), 128.1 (CH), 128.1 (CH), 128.3 (CH), 128.8 (CH), 129.3 (CH), 133.8 (Cq), 135.9 (Cq), 136.2 (Cq), 159.5 (Cq), 161.6 (Cq), 171.8 (Cq); HRMS (ESI) m/z calcd for C28H30O3Na [MþNa]þ 437.2093, found 437.2091. 4.15. (Z)-7-Allyl-3-benzylidene-6-methyl-2-phenyl-2,3dihydro-4H-furo[3,2-c]pyran-4-one (3ia) Yield 72%; yellow plates (AcOEtehexane, mp 167.0e170.3  C); IR (ATR) 2921, 1703, 1554, 1493, 1446, 1368, 1238, 994, 910, 863, 749 cm1; 1H NMR (500 MHz, CDCl3) d 2.28 (3H, s), 3.06 (1H, dd, J¼16.0 and 5.5 Hz), 3.13 (1H, dd, J¼16.0 and 5.5 Hz), 4.96 (1H, d, J¼17.0 Hz), 5.01 (1H, d, J¼10.0 Hz), 5.75 (1H, ddt, J¼17.0, 10.0 and

5.5 Hz), 6.73 (1H, s), 7.04e7.17 (5H, m), 7.29e7.34 (3H, m), 7.39e7.44 (2H, m), 7.50 (1H, s); 13C NMR (125 MHz, CDCl3) d 17.4 (CH3), 28.0 (CH2), 89.9 (CH), 103.7 (Cq), 105.9 (Cq), 115.9 (CH2), 121.1 (CH), 126.6 (CH), 128.2 (CH), 128.4 (CH), 128.9 (CH), 129.4 (CH), 133.6 (CH), 133.6 (Cq), 135.8 (Cq), 136.1 (Cq), 159.4 (Cq), 162.7 (Cq), 171.5 (Cq); HRMS (ESI) m/z calcd for C24H20O3Na [MþNa]þ 379.1310, found 379.1307. 4.16. (Z)-3-Benzylidene-7-(4-fluorobenzyl)-6-methyl-2phenyl-2,3-dihydro-4H-furo[3,2-c]pyran-4-one (3ja) Yield 48%; yellow needles (AcOEtehexane, mp 189.2e192.5  C); IR (ATR) 1726, 1557, 1508, 1446, 1240, 1205, 1057, 1012, 908, 868, 785, 742 cm1; 1H NMR (500 MHz, CDCl3) d 2.29 (3H, s), 3.66 (2H, s), 6.72 (1H, d, J¼2.5 Hz), 6.86 (2H, t, J¼8.5 Hz), 6.98e7.03 (2H, m), 7.05e7.17 (5H, m), 7.28e7.34 (3H, m), 7.37e7.41 (2H, m), 7.50 (1H, d, J¼3.0 Hz); 13C NMR (125 MHz, CDCl3) d 17.7 (CH3), 29.0 (CH2), 90.0 (CH), 103.9 (Cq), 107.5 (Cq), 115.3 (CH, d, J¼21.9 Hz), 121.4 (CH), 126.7 (CH), 128.1 (CH), 128.2 (CH), 128.4 (CH), 128.9 (CH), 129.3 (CH), 129.4 (CH, d, J¼9.4 Hz), 133.3 (Cq), 133.9 (Cq, d, J¼2.9 Hz), 135.7 (Cq), 136.0 (Cq), 159.2 (Cq), 161.5 (Cq, d, J¼243.8 Hz), 162.7 (Cq), 171.2 (Cq); HRMS (ESI) m/z calcd for C28H21FO3Na [MþNa]þ 447.1372, found 447.1375. 4.17. (Z)-3-Benzylidene-7-{3-(tert-butyldimethylsilyl)-2propyn-1-yl}-6-methyl-2-phenyl-2,3-dihydro-4H-furo[3,2-c] pyran-4-one (3ka) Yield 72%; yellow needles (acetoneehexane, mp 170.0e174.8  C); IR (KBr) 2952, 2928, 2856, 2175, 1730, 1559 cm1; 1 H NMR (400 MHz, CDCl3) d 0.03 (6H, s), 0.86 (9H, s), 2.39 (3H, s), 3.25 (1H, d, J¼18.0 Hz), 3.33 (1H, d, J¼18.0 Hz), 6.74 (1H, d, J¼2.8 Hz), 7.05e7.12 (3H, m), 7.12e7.16 (2H, m), 7.30e7.34 (3H, m), 7.40e7.44 (2H, m), 7.49 (1H, d, J¼2.8 Hz); 13C NMR (100 MHz, CDCl3) d 4.7 (CH3), 15.0 (CH2), 16.4 (Cq), 17.7 (CH3), 26.0 (CH3), 84.2 (Cq), 90.3(CH), 101.8 (Cq), 103.7 (Cq), 104.4 (Cq), 121.3 (CH), 126.7 (CH), 128.2 (CH), 128.3 (CH), 128.4 (CH), 128.9 (CH), 129.4 (CH), 133.5 (Cq), 135.7 (Cq), 136.1 (Cq), 159.0 (Cq), 163.2 (Cq), 170.5 (Cq); HRMS (ESI) m/z calcd for C30H32NaO3Si [MþNa]þ 491.2018, found 491.2011. Acknowledgements This study was supported in part by a Grant-in-Aid for Scientific Research (C) Grant number 26460009 from the Japan Society for the Promotion of Science (JSPS). References and notes 1. (a) Tsuji, J. Palladium Reagents and Catalysts: Innovations in Organic Synthesis; Wiley: New York, NY, 1995; p 453; (b) Tsuji, J. Palladium Reagents and Catalysts: New Perspectives for the 21st Century; Wiley: England, UK, 2004; p 543; (c) Tsuji, J.; Mandai, T. Angew. Chem., Int. Ed. 1995, 34, 2589; (d) Guo, L.-N.; Duan, X.-H.; Liang, Y.-M. Acc. Chem. Res. 2011, 44, 111; (e) Yoshida, M. Chem. Pharm. Bull. 2012, 60, 285; (f) Yoshida, M. Heterocycles 2013, 87, 1835. 2. (a) Tsuji, J.; Watanabe, H.; Minami, I.; Shimizu, I. J. Am. Chem. Soc. 1985, 107, 2196; (b) Minami, I.; Yuhara, M.; Watanabe, H.; Tsuji, J. J. Organomet. Chem. 1987, 334, 225; (c) Geng, L.-F.; Lu, X.-Y. Chin. J. Chem. 1993, 11, 91; (d) Labrosse, J.-R.; Lhoste, P.; Sinou, D. Tetrahedron Lett. 1999, 40, 9025; (e) Labrosse, J.-R.; Lhoste, P.; Sinou, D. Org. Lett. 2000, 2, 527; (f) Damez, C.; Labrosse, J.-R.; Lhoste, P.; Sinou, D. Tetrahedron Lett. 2003, 44, 557; (g) Duan, X.-H.; Liu, X.-Y.; Guo, L.-N.; Liao, M.-C.; Liu, W.-M.; Liang, Y.-M. J. Org. Chem. 2005, 70, 6980; (h) Yoshida, M.; Higuchi, M.; Shishido, K. Tetrahedron Lett. 2008, 49, 1678; (i) Yoshida, M.; Higuchi, M.; Shishido, K. Org. Lett. 2009, 11, 4752; (j) Yoshida, M.; Higuchi, M.; Shishido, K. Tetrahedron 2010, 66, 2675; (k) Yoshida, M.; Sugimura, C.; Shishido, K. Org. Lett. 2011, 13, 3482; (l) Yoshida, M.; Ohno, S.; Shishido, K. Chem.dEur. J. 2012, 18, 1604; (m) Yoshida, M.; Sugimura, C. Tetrahedron Lett. 2013, 54, 2082; (n) Yoshida, M.; Nakagawa, T.; Kinoshita, K.; Shishido, K. J. Org. Chem. 2013, 78, 1687; (o) Iwata, A.; Inuki, S.; Oishi, S.; Fujii, N.; Ohno, H. Chem. Commun. 2014, 298; (p) Montgomery, T. D.; Nibbs, A. E.; Zhu, Y.; Rawal, V. H. Org. Lett. 2014, 16, 3480; (q) Gao, R.-D.; Liu, C.; Dai, L.-X.; Zhang, W.; You, S.-L. Org. Lett. 2014, 16, 3919; (r) Nibbs, A. E.;

M. Yoshida et al. / Tetrahedron 72 (2016) 5633e5639

3.

4.

5.

6.

Montgomery, T. D.; Zhu, Y.; Rawal, V. H. J. Org. Chem. 2015, 80, 4928; (s) Zhou, Y.; Zhu, F.-L.; Liu, Z.-T.; Zhou, X.-M.; Hu, X.-P. Org. Lett. 2016, 18, 2734. Palladium-catalyzed direct coupling reaction of propargylic alcohols with arylboronic acids has been reported. (a) Yoshida, M.; Gotou, T.; Ihara, M. Tetrahedron Lett. 2004, 45, 5573; (b) Green, N. J.; Willis, A. C..; Sherburn M. S. Angew. Chem. Int. Ed. Early View (DOI: 10.1002/anie.201604527). (a) Muzart, J. Eur. J. Org. Chem. 2007, 3077; (b) Bandini, M.; Cera, G.; Chiarucci, M. Synthesis 2012, 44, 504; (c) Sundararaju, B.; Achard, M.; Bruneau, C. Chem. Soc. Rev. 2012, 41, 4467; (d) Kumar, R.; Van der Eycken, E. V. V. Chem. Soc. Rev. 2013, 42, 1121; (e) Butt, N. A.; Zhang, W. Chem. Soc. Rev. 2015, 44, 7929; (f) Yang, Q.; Wang, Q.; Yu, Z. Chem. Soc. Rev. 2015, 44, 2305. (a) Tamaru, Y.; Horino, Y.; Araki, M.; Tanaka, S.; Kimura, M. Tetrahedron Lett. 2000, 41, 5705; (b) Horino, Y.; Naito, M.; Kimura, M.; Tanaka, S.; Tamaru, Y. Tetrahedron Lett. 2001, 42, 3113; (c) Shue, Y.; Yang, S.; Lai, H. Tetrahedron Lett. 2003, 44, 1481; (d) Takacs, J. M.; Jiang, X.-T.; Leonov, A. P. Tetrahedron Lett. 2003, 44, 7075; (e) Kimura, M.; Mukai, R.; Tanigawa, N.; Tanaka, S.; Tamaru, Y. Tetrahedron 2003, 59, 7767; (f) Mukai, R.; Horino, Y.; Tanaka, S.; Tamaru, Y.; Kimura, M. J. Am. Chem. Soc. 2004, 126, 11138; (g) Kimura, M.; Futamata, M.; Shibata, K.; Tamaru, Y. Chem. Commun. 2003, 234; (h) Kimura, M.; Futamata, M.; Mukai, R.; Tamaru, Y. J. Am. Chem. Soc. 2005, 127, 4592; (i) Trost, B. M.; Quancard, J. J. Am. Chem. Soc. 2006, 128, 6314; (j) Olsson, V. J.; Sebelius, S.; Selander, , K. J. J. Am. Chem. Soc. 2006, 128, 4588; (k) Selander, N.; Paasch, J. R.; N.; Szabo  , K. J. J. Am. Chem. Soc. 2011, 133, 409. Szabo (a) Manabe, K.; Kobayashi, S. Org. Lett. 2003, 5, 3241; (b) Yang, S.; Hsu, Y.; Gan, K. Tetrahedron 2006, 62, 3949; (c) Gan, K.-H.; Jhong, C.-J.; Yang, S.-C. Tetrahedron 2008, 64, 1204; (d) Jiang, G.; List, B. Angew. Chem., Int. Ed. 2011, 50, 9471; (e) Hikawa, H.; Yokoyama, Y. J. Org. Chem. 2011, 76, 8433; (f) Hikawa, H.; Yokoyama, Y. Org. Lett. 2011, 13, 6512; (g) Hikawa, H.; Yokoyama, Y. Org. Biomol. Chem. 2011, 9, 4044; (h) Tao, Z.-L.; Zhang, W.-Q.; Chen, D.-F.; Adele, A.; Gong, L.-Z. J. Am. Chem. Soc. 2013, 135, 9255; (i) Zhou, H.; Yang, H.; Liu, M.; Xia, C.; Jiang, G. Org. Lett. 2014, 16, 5350; (j) Banerjee, D.; Junge, K.; Beller, M. Angew. Chem., Int. Ed.

7.

8. 9. 10.

11. 12. 13.

5639

2014, 53, 13049; (k) Yoshida, M.; Masaki, E.; Terumine, T.; Hara, S. Synthesis 2014, 46, 1367; (l) Lang, S. B.; Locascio, T. M.; Tunge, J. A. Org. Lett. 2014, 16, 4308; (m) Hikawa, H.; Izumi, K.; Ino, Y.; Kikkawa, S.; Yokoyama, Y.; Azumaya, I. Adv. Synth. Catal. 2015, 357, 1037. (a) Ozawa, F.; Okamoto, H.; Kawagishi, S.; Yamamoto, S.; Minami, T.; Yoshifuji, M. J. Am. Chem. Soc. 2002, 124, 10968; (b) Ozawa, F.; Ishiyama, T.; Yamamoto, S.; Kawagishi, S.; Murakami, H. Organometallics 2004, 23, 1698; (c) Kinoshita, H.; Shinokubo, H.; Oshima, K. Org. Lett. 2004, 6, 4085; (d) Kayaki, Y.; Koda, T.; Ikariya, T. J. Org. Chem. 2004, 69, 2595; (e) Murakami, H.; Matsui, Y.; Ozawa, F.; Yoshifuji, M. J. Organomet. Chem. 2006, 691, 3151; (f) Usui, I.; Schmidt, S.; Keller, M.; Breit, B. Org. Lett. 2008, 10, 1207; (g) Nishikata, T.; Lipshutz, B. H. Org. Lett. 2009, 11, 2377; (h) Tao, Y.; Wang, B.; Wang, B.; Qu, L.; Qu, J. Org. Lett. 2010, 12, 2726; (i) Ghosh, R.; Sarkar, A. J. Org. Chem. 2011, 76, 8508; (j) Tsupova, S.; Maeorg, U. Org. Lett. 2013, 15, 3381; (k) Gumrukcu, Y.; De Bruin, B.; Reek, J. N. H. ChemSusChem 2014, 7, 890; (l) Huo, X.; Yang, G.; Liu, D.; Liu, Y.; Gridnev, I. D.; Zhang, W. Angew. Chem., Int. Ed. 2014, 53, 6776. ()-BINAP was used in any cases. When the reaction using optically active BINAP was carried out, the racemic product was only obtained. We also examined the reactions using monoaryl-substituted substrates such as 1- or 3-phenylprop-2-yn-1-ol, but it resulted in the formation of complex mixture. Crystallographic data (excluding structure factors) for the structures in this paper have been deposited with the Cambridge Crystallographic Data Centre as supplementary publication number CCDC 1486332. Copies of the data can be obtained, free of charge, on application to CCDC, 12 Union Road, Cambridge CB2 1EZ, UK [fax: þ44(0) 1223 336033 or e-mail: [email protected]]. Tsutsumi, K.; Kawase, T.; Kakiuchi, K.; Ogoshi, S.; Okada, Y.; Kurosawa, H. Bull. Chem. Soc. Jpn. 1999, 72, 2687. We previously reported the palladium-catalyzed cyclization of 4-hydroxy-2pyrones with propargylic carbonates, see ref. 2n. Yoshida, M.; Takai, H.; Shishido, K. Heterocycles 2010, 82, 881.