Manganese(III) acetate based oxidative cyclizations of3-oxopropanenitriles with conjugated alkenes and synthesis of

4,5-dihydrofuran-3-carbonitriles containing heterocycles

Mehmet Yılmaz,* Nese Uzunalioglu and A. Tarık Pekel

Department of Chemistry, Science Faculty, Ankara University, Tandogan, 06100 Ankara, Turkey

Received 29 April 2005; revised 20 June 2005; accepted 7 July 2005

Available online 26 July 2005

Abstract—4,5-Dihydrofuran-3-carbonitriles 3a–i were obtained through oxidative cyclizations of 3-oxo-3-phenylpropanenitrile 1a, 3-oxo-3-thien-2-ylpropanenitrile 1b, 3-(2-furyl)-3-oxopropanenitirle 1c, 3-(1-benzofuran-2-yl)-3-oxopropanenitrile 1d, and 4,4-dimethyl-3-oxopropanenitrile 1emediated manganese(III) acetate with 1,1-diphenyl-1-butene 2a and 1,2-diphenyl-1-pentene 2b. The treatments of these3-oxopropanenitriles with 2-thienyl substituted alkenes such as 2-[(E)-2-phenylvinyl]thiophene 2c, 2-[(E)-1-methyl-2-phenylvinyl]thio-phene 2d, and 2-(1-phenylvinyl)thiophene 2e formed 5-(2-thienyl)-4,5-dihydrofuran-3-carbonitriles 3j–r in good yields (45–93%). As aresult, 2-thienyl substituted alkenes formed products in higher yields than phenyl substituted derivatives.q 2005 Elsevier Ltd. All rights reserved.

1. Introduction

Oxidative cyclization reactions have become increasinglyimportant in the synthesis of useful and complex moleculesin the past two decades.1 The oxidative addition of carbon-centered radicals to alkenes mediated by transition metalsalts (MnC3, CeC4, CoC3, CuC2, etc.) has receivedconsiderable attention in the organic synthesis for theconstruction of carbon–carbon bonds. Among these,manganese(III) acetate1c–e,2 and cerium(IV) ammoniumnitrate2h,3 encompasses a prominent place and have beenused efficiently. Thus, they provide the formation of highlyfunctionalized products by inter- and intramolecularcyclization, such as, furans,1d,2i,k,4 g-lactones,5 b-lactams,6

biologically active compounds and natural products.1d,e,7

The oxidative cyclizations of active methylene compounds,which can be enolized such as 1,3-dicarbonyls, b-ketoestersand b-ketoamides using manganese(III) acetate withalkenes were studied in detail and various 4,5-dihydrofuranswere obtained.2c–k

Recently, we have reported the formation of 4,5-dihydro-furan and furan derivatives as a result of oxidativecyclizations of 1,3-dicarbonyl compounds with alkenesand alkynes2k by using Mn(OAc)3. Additionally, we have

0040–4020/$ - see front matter q 2005 Elsevier Ltd. All rights reserved.doi:10.1016/j.tet.2005.07.019

Keywords: Manganese(III) acetate; Oxidative cyclization; Heterocycles;4,5-Dihydrofuran-3-carbonitrile; 3-Oxopropanenitrile; Conjugated alkene.* Corresponding author. Tel.: 90 312 2126720; fax: 90 312 2232395;e-mail: meyilmaz@science.ankara.edu.tr

reported the synthesis of carbamoyl-4,5-dihydrofurans andtetralones due to the reaction of 1,3-dicarbonyls witha,b-unsaturated amides.2j Previously, we have describedthe synthesis of 3-trifluoroacetyl-4,5-dihydrofurans and3-(dihydrofuran-2(3H)-ylidene)-1,1,1-trifluoroacetones bythe treatment of trifluoromethyl-1,3-dicarbonyl compoundswith conjugated alkenes.8

The oxidative cyclizations of 3-oxopropanenitriles with1,1-diarylethylenes and their reaction mechanism have beenreported by Nishino et al.9 Here we studied oxidativecyclization of various 3-oxopropanenitriles 1a–g mediatedMn(OAc)3 with 1,1-diphenyl 2a and 1,2-diphenyl 2btrisubstituted sterically hindered alkenes, and 2-thienylsubstitute alkenes 2c–e comparatively. As a result of thesereactions we have obtained 4,5-dihydrofuran-3-carbonitrilescontaining heterocycles.

2. Results and discussion

Manganese(III) acetate dihydrate used as a radical oxidanthas been obtained from the bipolar packed-bed reactor byelectrochemical method in literature.10 Conjugated alkenes2b–d were synthesized using benzyltriphenylphosphoniumbromide and suitable carbonyl compounds.11 2a and 2ewere prepared by removing water from the carbinols, whichformed the reaction of phenylmagnesium bromide andsuitable carbonyl compounds.12 All 3-oxopropanenitriles1a–g were prepared according to literature.13

Tetrahedron 61 (2005) 8860–8867

M. Yılmaz et al. / Tetrahedron 61 (2005) 8860–8867 8861

Oxidative cyclizations have been carried out at 2:1:3 molratio (1–2–Mn(OAc)3) under N2 atmosphere in AcOH. Thereactions of 2a and 2b with 3-oxopropanenitriles at 80 8Cand the reactions of 2-thienyl substituted alkenes 2c–e with3-oxopropanenitriles at 60 8C produced 4,5-dihydrofuran-3-carbonitriles in good yields. All compounds purifiedthrough column chromatography or preparative TLC werecharacterized by IR, 1H NMR, 13C NMR, MS andmicroanalysis.

The results of the reactions of 1a–ewith 2a and 2b are givenin Table 1. The treatment of 1a with 2a formed 3a ingood yield (63%, entry 1), however we have obtained

Table 1. Oxidative cyclization of 3-oxopropanenitriles 1a–e with 2a and 2b

Entry 3-Oxopropanenitrile Alkene

1

1a

2a

2

1b

2a

3

1c

2a

4

1d

2a

5

1e

2a

6

1a2b

7

1b

2b

8

1c

2b

9

1d

2b

a Yield of isolated product based on the alkene.

4,5-dihydrofuran-3-carbonitrile 3f in low yield (40%,entry 6) as a result of the treatment of 1a with 2b. Also,the reactions of 3-oxopropanenitriles 1b–d containingheterocycles with 2a gave 3b–d in moderate yields (entries2–4). On the other hand, oxidative cyclizations of 1b–dwith2b gave 4,5-dihydrofuran-3-carbonitriles 3g–i in low yields(entries 7–9).

From these results we can conclude that 1,1-diphenylsubstituted alkene 2a is more reactive than 1,2-diphenylsubstituted alkene 2b. This high reactivity can be explainedby the stability of the intermediate products formed with theaddition of an a-carbon radical, which was obtained by the

4,5-Dihydrofuran-3-carbonitrile Yield (%)a

3a (63)

3b (44)

3c (42)

3d (55)

3e (48)

3f (40)

3g (26)

3h (23)

3i (30)

Table 2. Synthesis of heterocycles containing 4,5-dihydrofuran-3-carbonitriles

Entry 3-Oxopropanenitrile Alkene 4,5-Dihydrofuran-3-carbonitrile Yield (%)a

1

1a 2c

3j (56)

2

1f

2c 3k (60)

3

1c

2c 3l (58)

4

1d

2c 3m (52)

5

1c2d

3n (67)

6

1d

2d 3o (60)

7

1f

2d 3p (71)

8

1f 2e

3r (83)

9

1g

2e 3s (93)

a Yield of isolated product based on the alkene.

M. Yılmaz et al. / Tetrahedron 61 (2005) 8860–88678862

treatment of Mn(OAc)3 and 3-oxopropanenitrile, to 2a.Both of the intermediate products are tertiary carbonradicals but the stability of tertiary radical formed on 2a ishigher than that of the tertiary radical formed on 2b since thetertiary radical of 2a is conjugated with phenyl groups, andthe cyclization of more stable intermediate product forms4,5-dihydrofuran-3-carbonitrile in a higher yield.

Oxidative cyclizations of 2-thienyl substituted alkenesmediated manganese(III) acetate with 3-oxopropanenitrilesand the other active methylene compounds have not beenstudied so far. Herein, we first reported the reactions of these

alkenes 2c–e with 3-oxopropanenitriles and the synthesis of4,5-dihydrofuran-3-carbonitrile containing heterocycles(Table 2).

There are two possible ways in oxidative cyclization of3-oxopropanenitriles with 2c. In one of them 4-(2-thienyl)substituted 4,5-dihydrofurans can be formed, in the otherone 5-(2-thienyl) substituted 4,5-dihydrofurans can beformed. The mechanism of these possible cyclizations isexplained in Scheme 1. According to this mechanism,Mn(OAc)3 with the enol form of 3-oxo-propanenitrile Agives manganese(III)-enolate complex B. In complex B, an

Scheme 1.

M. Yılmaz et al. / Tetrahedron 61 (2005) 8860–8867 8863

a-carbon radical C is formed on 3-oxopropanenitrile whileMnC3 is reduced to MnC2. This a-carbon radical attacks to2c, and compound D can be formed with the followingpathway i, or compoundG can be formed with the followingpathway ii. Structure D is oxidized to carbocation Ewith Mn(OAc)3 and intermolecular cyclization of Eforms 5-(2-thienyl) substituted 4,5-dihydrofuran F. Struc-ture G following the same two steps forms 4-(2-thienyl)substituted 4,5-dihydrofuran H. In literature the chemicalshifts of H4 and H5 have been reported as 4.4 and 5.6 ppmaccording to its 1H NMR spectrum.9 However, it has beenobserved that in the 1H NMR spectra of the compounds3j–m that we have synthesized, H4 and H5 gave thechemical shifts of 4.58–4.88 and 6.02–6.11 ppm, respect-ively. According to these results, it has been concluded that5-(2-thienyl) substituted 4,5-dihydrofurans F are producedfrom path i.

Nishino et al. obtained 2,4,5,-triphenyl-4,5-dihydrofuran-3-carbonitrile in 34% yield by the treatment of trans-stilbenewith 1a at reflux temperature.9 However, we have obtained2,4-diphenyl-5-thien-2-yl-4,5-dihydrofuran-3-carbonitrile3j in 56% yield by the treatment of 1a with 2-[(E)-2-phenylvinyl]thiophene 2c. Oxidative cyclizations of 3-oxo-propanenitriles containing 2-furyl 1c and 2-benzofuryl 1dwith 2c gave 3l (58%) and 3m (52%) 4,5-dihydrofuran-3-carbonitriles, respectively (entries 3 and 4). In NMRspectra, the coupling constants (JZ7.3–7.7 Hz) of H4 andH5 protons of 3j–m show that 2-thienyl and phenyl groupsare in trans position.

It has been mentioned that oxidative cyclization of3-oxopropanenitriles with 2b produces 4,5-dihydrofuran-3-carbonitriles in low yields in Table 1. Yet, the treatmentsof 2-[(E)-1-methyl-2-phenylvinyl]thiophene 2d with 1cand 1d gave 3n and 3o in good yields, respectively (entries5 and 6).

Additionally, the reaction of 1f with 2d gave 4,5-di-hydrofuran-3-carbonitrile 3p in 71% yields. In literature,the reactions of 1f and 1g with 1,1-diphenylethylene at

reflux temperature gave 4,5-dihidrofurans in 67 and 74%yields, respectively.9 However, we obtained 5-(2-thienyl)substituted 4,5-dihydrofuran-3-carbonitriles 3r in 83% and3s in 93% yields, respectively, by the cyclization of 2-(1-phenylvinyl)thiophene 2e with 1f and 1g (entries 8 and 9).

Consequently, oxidative cyclizations of 3-oxopropane-nitriles mediated manganese(III) acetate with 1,1 and 1,2-diphenyl substituted alkenes and 2-thienyl substitutedderivatives have comparatively been studied in this work.As a result, 2-thienyl substituted alkenes formed products inhigher yields than phenyl substituted derivatives.

3. Experimental

Melting points were determined on a Gallencamp capillarymelting point. IR spectra (KBr disc) were obtained with aMatson 1000 FT-IR in the 400–4000 cmK1 range with4 cmK1 resolution. 1H NMR (400 MHz), and 13C NMR(100 MHz) spectra were recorded on a Bruker AvanceDPX- 400 MHz high performance digital FT NMR inCDCl3 solution. The electron impact mass spectra weremeasured on a Agilent 1100 MSD LC/MS (APCI, 100–150 eV), and a Shimadzu GC-17A/GC-MS-QP5000 (EIMS,70 eV) spectrophotometers. Elemental analyses wereperformed on a Leco 932 CHNS-O instrument.

Thin layer chromatography (TLC) was performed on Merckaluminum-packed silica gel plates. Purification of productswas performed by column chromatography on silica gel(Merck silica gel 60, 40–63 mm) or preparative TLC onsilica gel of Merck (PF254–366 nm). All solvents purchasedfrom DOP.

3.1. General procedure for synthesis of 4,5-dihydro-furan-3-carbonitriles

A solution of manganese(III) acetate dihydrate (6 mmol,1.64 g) in 30 mL in glacial acetic acid was heated undernitrogen atmosphere at 80 8C until it dissolved. After

M. Yılmaz et al. / Tetrahedron 61 (2005) 8860–88678864

Mn(OAc)3 dissolved completely, the solution was cooleddown to 50 8C. A solution of 1a–f (4 mmol) and alkene(2 mmol) in 5 mL acetic acid was added to this mixture andthe temperature was raised up to 80 8C (for 2c–e at 60 8C).The reaction was completed when the dark brown colour ofthe solution disappeared (in 1–15 min). Acetic acid wasevaporated under reduced pressure. Water was added to theresidue and extracted with EtOAc (3!20 mL). Thecombined organic phases were neutralized with satdNaHCO3 solution, and dried over anhydrous Na2SO4.Crude products were purified by column chromatographyon silica gel or preparative TLC (20!20 cm plates, 2 mmthickness) using n-hexane/ EtOAc (5:1) as eluent.

3.1.1. 4-Ethyl-2,5,5-triphenyl-4,5-dihydrofuran-3-carbo-nitrile (3a). Yield 63% (442 mg) as a colourless solid, mp143–144 8C (hexane/EtOAc). [Found: C, 85.7; H, 5.8; N,4.1. C25H21NO requires C, 85.4; H, 6.0; N, 4.0%]; nmax (KBrdisc) 2201 (CN), 1627 (C]C), 1234 (C–O–C), 756, 696; dH(400 MHz, CDCl3) 8.26 (2H, dd, JZ7.4, 1.7 Hz, arom.),7.76 (2H, dd, JZ7.5, 1.5 Hz, arom.), 7.67 (3H, m, arom.),7.56 (2H, tt, JZ7.0, 1.6 Hz, arom.), 7.52–7.44 (6H, m,arom.), 4.04 (1H, dd, JZ7.7, 5.9 Hz, H4), 1.56 (2H, m,CHCH2Me), 1.14 (3H, t, JZ7.4 Hz, Me); dC (100 MHz,CDCl3) 165.3 (C2), 144.1, 140.5, 131.8, 129.1, 128.7,128.5, 128.4, 128.3, 127.9, 127.6, 126.9, 126.4, 118.5 (CN),96.3 (C3), 85.8 (C5), 53.3 (C4), 26.4 (CH2Me), 11.8 (Me);m/z (APCI, 150 eV) 352 (MHC, 4.4), 351 (MC, 16.2), 336(MCKCH3, 4.7), 322 (MCKC2H5, 7.1), 306 (MCKC3H8,4.6), 246 (MCKPhCO, 3.1), 167 (C13H11

C, 4.1), 105(PhCOC, 100.00), 91 (PhCH2

C, 5.01), 77 (C6H5C, 48.6).

3.1.2. 4-Ethyl-5,5-diphenyl-2-thien-2-yl-4,5-dihydro-furan-3-carbonitrile (3b). Yield 44% (314 mg) as acolourless oil. [Found: C, 77.1; H, 5.6; N, 4.1; S, 8.8.C23H19NOS requires C, 77.3; H, 5.4; N, 3.9; S, 9.0%]; nmax

(KBr disc, CHCl3) 2198 (CN), 1616 (C]C), 1211 (C–O–C), 731, 696; dH (400 MHz, CDCl3) 7.88 (1H, d, JZ3.8 Hz,arom.), 7.51 (1H, d, JZ7.2 Hz, arom.), 7.48 (1H, d, JZ5.0 Hz, arom.), 7.32 (1H, t, JZ7.8 Hz, arom.), 7.26–7.19(7H, m, arom.), 7.09 (1H, t, JZ4.8 Hz, arom.), 3.76 (1H, t,JZ6.9 Hz, H4), 1.41 (2H, m, CHCH2Me), 0.89 (3H, t, JZ7.4 Hz, Me); m/z (APCI, 150 eV) 358 (MHC, 1.6), 357(MC, 6.5), 342 (MCKCH3, 2.6), 328 (MCKC2H5, 4.2),312 (MCKC3H8, 3.2), 274 (M

CKC4H3S, 4.7), 246 (MCK

C5H3SO, 9.9), 231 (MCKC5H3SOKCH3, 6.3), 165(C13H9

C, 6.7), 111 (C5H3SOC, 100.00), 105 (PhCOC,

3.9), 91 (PhCH2C, 4.0), 83 (C4H3S

C, 5.01).

3.1.3. 4-Ethyl-5,5-diphenyl-4,5-dihydro-2,2 0-bifuran-3-carbonitrile (3c). Yield 42% (86 mg) as a colourlesssolid, mp 133–134 8C (hexane/EtOAc). [Found: C, 80.7; H,5.6; N, 3.8. C23H19NO2 requires C, 80.9; H, 5.6; N, 4.1%];nmax (KBr disc) 2970, 2876, 2201 (CN), 1635 (C]C), 1180(C–O–C), 764, 702; dH (400 MHz, CDCl3) 7.85 (1H, d, JZ1.4 Hz, arom.), 7.79 (2H, d, JZ7.4 Hz, arom.), 7.62 (1H, t,JZ6.9 Hz, arom.), 7.58–7.50 (7H, m, arom.), 7.34 (1H, d,JZ3.5 Hz, arom.), 6.79 (1H, dd, JZ3.5, 1.7 Hz, arom.),4.05 (1H, t, JZ6.8 Hz, H4), 1.58 (2H, m, CHCH2Me), 1.28(3H, t, JZ7.4 Hz, Me); dC (100 MHz, CDCl3) 156.8 (C2),145.7, 144.1, 143.7, 140.1, 128.7, 128.6, 128.3, 127.9,126.8, 126.3, 117.5 (CN), 114.5, 112.4, 97.2 (C3), 84.5(C5), 52.8 (C4), 26.3 (CH2Me), 11.7 (Me); m/z (APCI,

150 eV) 342 (MHC, 5.8), 341 (MC, 21.1), 326 (MCKCH3,7.7), 312 (MCKC2H5, 10.5), 295 (MCKC3H8, 9.01), 274(MCKC4H3O, 12.5), 246 (MCKC5H3O2, 83.6), 232(MCKC5H3O2KCH3, 52.3), 217 (MCKC5H3O2KC2H5,13.3), 207 (MCKC10H14, 3.8), 167 (C13H11

C, 22.8), 152(C12H10

C, 23.1), 105 (PhCOC, 6.5), 217 (C5H3O2C, 100.00),

91 (PhCH2C, 12.10), 77 (C6H5

C, 1.2).

3.1.4. 2-(1-Benzofuran-2-yl)-4-ethyl-5,5-diphenyl-4,5-dihydrofuran-3-carbonitrile (3d). Yield 55% (430 mg)as a colourless solid, mp 186 8C (hexane/ EtOAc). [Found:C, 82.6; H, 5.1; N, 3.5. C27H21NO2 requires C, 82.8; H, 5.4;N, 3.6%]; nmax (KBr disc) 2201 (CN), 1639 (C]C), 1180(C–O–C), 754, 698; dH (400 MHz, CDCl3) 7.58 (1H, d, JZ7.9 Hz, arom.), 7.53 (2H, m, arom.), 7.38 (1H, s, arom.),7.32 (1H, t, JZ7.9 Hz, arom.), 7.28–7.19 (10H, m, arom.),3.80 (1H, dd, JZ7.5, 6.2 Hz, H4), 1.41 (2H, m, CHCH2Me),1.03 (3H, t, JZ7.5 Hz, Me); m/z (APCI, 150 eV) 392(MHC, 6.8), 391 (MC, 23.4), 376 (MCKCH3, 10.3), 362(MCKC2H5, 4.8), 346 (MCKC3H8, 7.3), 274 (MCKC8H5O, 12.8), 246 (M

CKC9H5O2, 15.7), 167 (C13H11C, 5.7),

145 (C9H5O2C, 92.6), 89 (C7H5

C, 100.0).

3.1.5. 2-tert-Butyl-4-ethyl-5,5-diphenyl-4,5-dihydro-furan-3-carbonitrile (3e). Yield 48% (318 mg) as acolourless solid, mp 99 8C (hexane/EtOAc). [Found: C,83.2; H, 7.7; N, 4.0. C23H25NO requires C, 83.3; H, 7.6; N,4.2%]; nmax (KBr disc) 2970, 2876, 2201 (CN), 1635(C]C), 1180 (C–O–C), 765, 702; dH (400 MHz, CDCl3)7.55 (2H, m, arom.), 7.38–7.21 (8H, m, arom.), 3.67 (1H,dd, JZ7.3, 5.8 Hz, H4), 1.42 (9H, s, 3!Me), 1.32 (2H, m,CHCH2Me), 0.84 (3H, t, JZ7.4 Hz, Me); m/z (APCI,150 eV) 332 (MHC, 5.6), 331 (MC, 22.01), 316 (MCKCH3, 3.4), 248 (MCKC6H11, 22.2), 246 (MCKC5H9O,11.3), 219 (MCKCNKC5H9O, 100.00), 196 (MCKPhCOKC2H4, 3.9), 167 (C13H11

C, 10.1), 152 (C12H10C, 5.4),

105 (PhCOC, 8.6), 91 (PhCH2C, 9.2), 57 (C4H9

C, 29.2).

3.1.6. 2,4,5-Triphenyl-5-propyl-4,5-dihydrofuran-3-carbonitrile (3f). Yield 40% (292 mg) as a pale yellowoil. [Found: C, 85.8; H, 6.1; N, 4.1. C26H23NO requires C,85.5; H, 6.3; N, 3.8%]; nmax (KBr disc, CHCl3) 2957, 2874,2203 (CN), 1623 (C]C), 760, 649; dH (400 MHz, CDCl3)8.00 (2H, dd, JZ7.9, 1.5 Hz, arom.), 7.34 (3H, t, JZ6.5 Hz,arom.), 7.20 (7H, m, arom.), 7.11 (3H, td, JZ7.5, 1.4 Hz,arom.), 4.07 (1H, s, H4), 1.32 (1H, m), 1.22 (1H, m), 1.12(1H, m), 0.55 (1H, m), 0.48 (3H, t, JZ7.3 Hz, Me); m/z(APCI, 150 eV) 366 (MHC, 18.9), 365 (MC, 63.1), 350(MCKCH3, 2.6), 322 (MCKC3H7, 3.6), 288 (MCKC6H5,4.1), 260 (MCKC7H5O, 1.3), 246 (MCKC6H5KC3H8,4.9), 179 (MCKC14H11, 4.1), 154 (C12H10

C, 5.5), 143(C11H11

C, 26.7), 128 (C9H6NC, 36.4), 105 (C7H5O

C, 77.6),91 (PhCH2

C, 100.00), 77 (C6H5C, 11.6).

3.1.7. 4,5-Diphenyl-5-propyl-2-thien-2-yl-4,5-dihydro-furan-3-carbonitrile (3g). Yield 26% (193 mg) as a paleyellow oil. [Found: C, 77.5; H, 5.5; N, 4.0; S, 8.5.C24H21NOS requires C, 77.6; H, 5.7; N, 3.8; S, 8.6%];nmax (KBr disc, CHCl3) 2955, 2876, 2203 (CN), 1617(C]C), 756, 701; dH (400 MHz, CDCl3) 7.83 (1H, d, JZ3.8 Hz), 7.40 (1H, d, JZ4.9 Hz, arom.), 7.23–7.08 (10H, m,arom.), 7.04 (1H, t, JZ4.8 Hz, arom.), 4.22 (1H, s, H4),1.31 (1H, td, JZ11.0, 4.7 Hz, CHaHbCH2Me), 1.20 (1H, td,

M. Yılmaz et al. / Tetrahedron 61 (2005) 8860–8867 8865

JZ11.3, 4.5 Hz, CHaHbCH2Me), 1.16 (1H, m), 0.66(1H, m), 0.45 (3H, t, JZ7.0 Hz, Me); m/z (APCI, 150 eV)372 (MHC, 11.6), 371 (MC, 42.4), 356 (MCKCH3, 1.6),328 (MCKC3H7, 2.6), 294 (MCKC6H5, 2.8), 288(MCKC4H3S, 18.7), 260 (MCKC5H3SO, 2.6), 245(MCKC4H3SKC3H7, 7.9), 223 (C10H12O

C, 7.9), 143(C11H11

C, 27.7), 128 (C9H6NC, 27.3), 111 (C5H3SO

C,30.6), 105 (C7H5O

C, 25.7), 91 (C7H7C, 100.00), 83

(C4H3SC, 2.5).

3.1.8. 4,5-Diphenyl-5-propyl-4,5-dihydro-2,2 0-bifuran-3-carbonitrile (3h). Yield 23% (163 mg) as a light yellow oil.[Found: C, 80.8; H, 6.2; N, 4.1. C24H21NO2 requires C, 81.1;H, 6.0; N, 4.0%]; nmax (KBr disc, CHCl3) 2961, 2874, 2207(CN), 1650 (C]C), 758, 702; dH (400 MHz, CDCl3) 7.62(1H, d, JZ0.9 Hz, arom.), 7.38–7.25 (10H, m, arom.), 7.23(1H, t, JZ7.0 Hz, arom.), 7.13 (1H, d, JZ3.7 Hz, arom.),6.56 (1H, dd, JZ3.4, 1.7 Hz, arom.), 4.41 (1H, s, H4), 1.48(1H, td, JZ11.3, 4.7 Hz, CHaHbCH2Me), 1.35 (1H, td,JZ11.5, 4.6 Hz, CHaHbCH2Me), 1.20 (1H, m), 0.81(1H, m), 0.52 (3H, t, JZ7.3 Hz, Me); m/z (APCI, 150 eV)356 (MHC, 19.7), 355 (MC, 71.3), 340 (MCKCH3, 3.2),313 (MHCKC3H7, 3.6), 288 (MCKC4H3O, 10.9),278 (MCKC6H5, 2.9), 260 (MCKC5H3O2, 12.9), 246(MCKC4H3OKC3H9, 17.1), 232 (MCKC7H7O2, 18.4),223 (MCKC10H12, 24.4), 210 (MCKC6H5KC4H3O, 4.5),178 (C14H10

C, 5.4), 143 (C11H11C, 27.8), 128 (C9H6N

C, 32.6),105 (C7H5O

C, 33.8), 95 (C5H3O2C, 31.6), 91 (C7H7

C,100.00), 77 (C6H5

C, 2.1).

3.1.9. 2-(1-Benzofuran-2-yl)-5-propyl-4,5-diphenyl-4,5-dihydrofuran-3-carbonitrile (3i). Yield 30% (243 mg) asa yellow oil. [Found: C, 83.1; H, 5.6; N, 3.3. C28H23NO2

requires C, 82.9; H, 5.7; N, 3.5%]; nmax (KBr disc, CHCl3)2209 (CN), 1648 (C]C), 1180 (C–O–C), 758, 702; dH(400 MHz, CDCl3) 7.72 (1H, d, JZ7.7 Hz, arom.), 7.56(1H, d, JZ8.4 Hz, arom.), 7.48 (1H, s, arom.), 7.48–7.35(12H, m, arom.), 4.63 (1H, s, H4), 1.86 (1H, td, JZ12.0,6.1 Hz, CHaHbCH2Me), 1.65 (1H, m), 1.52 (1H, td, JZ11.6,4.7 Hz, CHaHbCH2Me), 0.58 (1H, m), 0.54 (3H, t, JZ7.3 Hz, Me); m/z (APCI, 150 eV) 406 (MHC, 29.9), 405(MC, 100.00), 390 (MCKCH3, 3.2), 362 (M

CKC3H6, 2.3),228 (MCKC6H5, 3.5), 288 (MCKC8H5O, 37.0), 260(MCKC9H5O2, 5.5), 246 (MHCKC8H5OKC3H7, 15.2),145 (C9H5O2

C, 38.1), 105 (C7H5OC, 16.7), 91 (C7H7

C,48.2).

3.1.10. 2,4-Diphenyl-5-thien-2-yl-4,5-dihydrofuran-3-carbonitrile (3j). Yield 56% (369 mg) as a yellow oil.[Found: C, 76.3; H, 4.8; N, 4.2; S, 9.5. C21H15NOS requiresC, 76.6; H, 4.6; N, 4.3; S, 9.7%]; nmax (KBr disc, CHCl3)2203 (CN), 1623 (C]C), 1124 (C–O–C), 754, 700; dH(400 MHz, CDCl3) 8.32 (2H, dt, JZ6.7, 1.7 Hz, arom.),7.79–7.73 (3H, m, arom.), 7.67–7.56 (6H, m, arom.), 7.35(1H, dt, JZ3.0, 0.5 Hz, arom.), 7.28 (1H, dd, JZ3.6,5.1 Hz, arom.), 6.07 (1H, d, JZ7.3 Hz, H5), 4.84 (1H, d,JZ7.3 Hz, H4); dC (100 MHz, CDCl3) 166.6 (C-2), 141.9,139.3, 132.1, 129.7, 129.1, 128.6, 127.8, 127.7, 127.4,126.8, 126.4, 117.4 (CN), 88.4 (C3), 84.7 (C5), 59.1 (C4);m/z (EI, 70 eV) 330 (MHC, 19.57), 329 (MC, 81.05), 328(MCKH, 25.51), 252 (MCKC6H5, 4.33), 224 (MCKC6H5CO, 5.88), 105 (C6H5CO

C, 100.00), 83 (C4H3SC,

2.33), 77 (C6H5C, 47.02).

3.1.11. 2-(4-Methylphenyl)-4-phenyl-5-thien-2-yl-4,5-dihydofuran-3-carbonitrile (3k). Yield 60% (412 mg) asa yellow oil. [Found: C, 77.1; H, 5.2; N, 4.2; S, 9.5.C22H17NOS requires C, 76.9; H, 5.0; N, 4.1; S, 9.3%]; nmax

(KBr disc, CHCl3) 2203 (CN), 1617 (C]C), 1114 (C–O–C), 708; dH (400 MHz, CDCl3) 8.01 (2H, d, JZ8.3 Hz,arom.), 7.44–7.28 (8H, m, arom.), 7.12 (1H, d, JZ3.5 Hz,arom.), 7.05 (1H, dd, JZ5.0, 3.6 Hz, arom.), 6.02 (1H, d,JZ7.3 Hz, H5), 4.58 (1H, d, JZ7.3 Hz, H4), 2.45 (3H, s,Me); m/z (EI, 70 eV) 344 (MHC, 7.63), 343 (MC, 29.60),328 (MCKCH3, 6.76), 251 (M

CKC7H8, 2.33), 223 (MCK

C8H8O, 5.27), 119 (C8H6OC, 100.00), 91 (PhCH2

C, 63.68),77 (C6H5

C, 7.53).

3.1.12. 4-Phenyl-5-thien-2-yl-4,5-dihydro-2,2 0bifuran-3-carbonitrile (3l). Yield 58% (370 mg) as a yellow oil.[Found: C, 71.6; H, 3.8; N, 4.1; S, 10.2. C19H13NO2Srequires C, 71.5; H, 4.1; N, 4.4; S, 10.0%]; nmax (KBr disc,CHCl3) 2207 (CN), 1646 (C]C), 1174 (C–O–C), 758, 706;dH (400 MHz, CDCl3) 7.89 (1H, d, JZ1.2 Hz, arom.), 7.66–7.50 (8H, m, arom.), 7.27 (1H, dd, JZ5.1, 3.6 Hz, arom.),6.81 (1H, dd, JZ3.6, 1.7 Hz, arom.), 6.04 (1H, d, JZ7.7 Hz, H5), 4.82 (1H, d, JZ7.7 Hz, H4); m/z (EI,70 eV) 320 (MHC, 19.14), 319 (MC, 100.00), 236(MCKC4H3S, 3.85), 224 (MCKC5H3O2, 13.39), 178(MCKC10H7N, 15.11), 163 (C9H7OS

C, 10.96), 140(C10H6N

C, 51.87), 95 (C5H4O2C, 96.79), 83 (C4H3S

C,1.67), 77 (C6H5

C, 6.39).

3.1.13. 2-(1-Benzofuran-2-yl)-4-phenyl-5-thien-2-yl-4,5-dihydrofuran-3-carbonitrile (3m). Yield 52% (384 mg)as a colourless solid, mp 107–108 8C (hexane/EtOAc).[Found: C, 75.0; H, 4.1; N, 3.7; S, 8.6. C23H15NO2S requiresC, 74.8; H, 4.1; N, 3.8; S, 8.7%]; nmax (KBr disc) 2200 (CN),1643 (C]C), 1172 (C–O–C), 754, 700; dH (400 MHz,CDCl3) 7.92 (1H, d, JZ7.8 Hz, arom.), 7.85 (1H, d, JZ8.4 Hz, arom.), 7.69 (1H, s, arom.), 7.60–7.54 (8H, m,arom.), 7.37 (1H, d, JZ3.4 Hz, arom.), 7.28 (1H, dd, JZ5.0, 3.6 Hz, arom.), 6.11 (1H, d, JZ7.7 Hz, H5), 4.88(1H, d, JZ7.7 Hz, H4); m/z (EI, 70 eV) 370 (MHC, 22.68),369 (MC, 100.00), 285 (MCKC4H4S, 2.44), 227 (MHCKC8H5OKCN, 7.16), 145 (C9H5O2

C, 75.44), 83 (C4H3SC,

1.28), 89 (C7H5C, 58.15), 77 (C6H5

C, 6.4).

3.1.14. 5-Methyl-4-phenyl-5-thien-2-yl-4,5-dihydo-2,2 0bifuran-3-carbonitrile (3n). Yield 67% (446 mg) as ayellow oil. [Found: C, 72.2; H, 4.3; N, 4.0; S, 9.7.C20H15NO2S requires C, 72.1; H, 4.5; N, 4.2; S, 9.6%];nmax (KBr disc, CHCl3) 2205 (CN), 1629 (C]C), 1018(C–O–C), 754, 702; dH (400 MHz, CDCl3) 8.08 (2H, dt, JZ8.6, 1.9 Hz, arom.), 7.50 (2H, dt, JZ8.6, 1.9 Hz, arom.),7.45–7.35 (3H, m, arom.), 7.32 (1H, dd, JZ5.0, 1.2 Hz,arom.), 7.27 (1H, m, arom.), 7.10 (1H, dd, JZ3.7, 1.2 Hz,arom.), 7.05 (1H, dd, JZ5.0, 3.6 Hz, arom.), 4.79 (1H, s,H4), 1.47 (3H, s, Me); dC (100 MHz, CDCl3) 165.1 (C2),149.7, 137.9, 135.6, 129.2, 128.9, 128.85, 128.8, 128.5,127.1, 126.3, 124.9, 123.1, 117.1 (CN), 91.5 (C3), 84.3(C5), 61.8 (C4), 25.3 (Me); m/z (APCI, 100 eV) 334 (MHC,21.52), 333 (MC, 89.45), 316 (MHCKH2O, 17.42), 266(MCKC4H3O, 28.67), 239 (MHCKC5H3O2, 42.94), 224(MHCKC5H4OS, 13.81), 199 (MHCKC5H3O2KC2H2N,100.00), 95 (C5H3O2

C, 75.18).

M. Yılmaz et al. / Tetrahedron 61 (2005) 8860–88678866

3.1.15. 2-(1-Benzofuran-2-yl)-5-methyl-4-phenyl-5-thien-2-yl-4,5-dihydofuran-3-carbonitrile (3o). Yield60% (460 mg) as a colourless solid, mp 106–107 8C(hexane/EtOAc). [Found: C, 75.1; H, 4.4; N, 3.7; S, 8.4.C24H17NO2S requires C, 75.2; H, 4.5; N, 3.6; S, 8.3%]; nmax

(KBr disc) 2204 (CN), 1635 (C]C), 1132 (C–O–C), 751,694; dH (400 MHz, CDCl3) 7.65 (1H, d, JZ1.2 Hz, arom.),7.41–7.34 (5H, m, arom.), 7.28 (1H, dd, JZ5.2, 1.2 Hz,arom.), 7.25 (2H, dd, JZ6.8, 1.6 Hz, arom.), 7.13 (1H, d,JZ4.1 Hz, arom.), 7.07 (1H, dd, JZ3.6, 1.2 Hz, arom.),7.01 (1H, dd, JZ5.2, 3.2 Hz, arom.), 6.58 (1H, dd, JZ3.6,2.1 Hz, arom.), 4.70 (1H, s, H4), 1.38 (3H, s, Me); dC(100 MHz, CDCl3) 157.7 (C2), 149.5, 145.9, 143.6, 135.9,129.1, 129.0, 128.6, 127.2, 125.3, 123.65, 116.5 (CN),115.1, 112.3, 92.6 (C3), 82.7 (C5), 61.45 (C4), 60.65, 25.38,14.4 (Me); m/z (EI, 70 eV) 384 (MHC, 15.17), 383 (MC,58.51), 306 (MCKC6H5, 2.43), 257 (MCKC6H6OS,47.49), 238 (MCKC9H5O2, 15.51), 155 (MCKC9H5O2KC4H4S, 40.95), 145 (C9H5O2

C, 100.00), 126 (C6H6OSC,

15.55), 111 (C5H3OSC, 35.71), 83 (C4H3S

C, 9.45), 77(C6H5

C, 21.81).

3.1.16. 5-Methyl-2-(4-methylphenyl)-4-phenyl-5-thien-2-yl-4,5-dihydofuran-3-carbonitrile (3p). Yield 71%(507 mg) as a colourless solid, mp 152 8C (hexane/EtOAc). [Found: C, 77.1; H, 5.4; N, 4.2; S, 9.2.C23H19NOS requires C, 77.3; H, 5.3; N, 3.9; S, 9.0%];nmax (KBr disc) 2205 (CN), 1617 (C]C), 1238 (C–O–C),1078, 835, 696; dH (400 MHz, CDCl3) 8.04 (2H, d, JZ8.3 Hz, arom.), 7.44–7.27 (8H, m, arom.), 7.09 (1H, dd, JZ3.6, 1.2 Hz, arom.), 7.04 (1H, dd, JZ5.0, 3.6 Hz, arom.),4.71 (1H, s, H4), 2.46 (3H, s, Me), 1.41 (3H, s, Me); dC(100 MHz, CDCl3) 166.5 (C2), 150.1, 142.5, 136.1, 129.5,128.83, 128.8, 128.3, 127.4, 126.9, 125.1, 124.8, 123.1,117.7 (CN), 91.1 (C3), 82.9 (C5), 61.8 (C4), 25.3 (Me), 21.7(Me); m/z (APCI, 100 eV) 358 (MHC, 11.82), 357 (MC,74.01), 343 (MHCKCH3, 13.81), 238 (MCKC8H7O,35.24), 119 (C8H7O

C, 100.0), 91 (C7H7C, 19.12), 77

(C6H5C, 4.15).

3.1.17. 2-(4-Methylphenyl)-5-phenyl-5-thien-2-yl-4,5-dihydrofuran-3-carbonitrile (3r). Yield 83% (569 mg)as a yellow oil. [Found: C, 77.1; H, 5.3; N, 3.9; S, 9.5.C22H17NOS requires C, 76.9; H, 5.0; N, 4.1; S, 9.3%]; nmax

(KBr disc, CHCl3) 2198 (CN), 1608 (C]C), 1255 (C–O–C), 1182, 835, 704; dH (400 MHz, CDCl3) 8.0 (2H, d, JZ8.3 Hz, arom.), 7.50 (2H, dt, JZ6.9, 1.7 Hz, arom.), 7.38–7.44 (3H, m, arom.), 7.33 (3H, m, arom.), 7.0 (2H, m,arom.), 3.89 (1H, d, JZ14.8 Hz, Ha4), 3.71 (1H, d, JZ14.8 Hz, Hb4), 2.45 (3H, s, Me); dC (100 MHz, CDCl3)166.4 (C2), 148.9, 144.5, 143.1, 130.3, 129.4, 129.2, 128.1,127.5, 127.1, 126.6, 126.0, 125.9, 118.1 (CN), 91.1 (C3),78.7 (C5), 47.3 (C4), 21.8 (Me); m/z (APCI, 150 eV) 344(MHC, 16.8), 343 (MC, 29.8), 328 (MCKCH3, 28.79), 276(MCKC4H3S, 43.23), 224 (MCKC8H7O, 25.70), 155(MHCKC11H8OS, 34.45), 119 (C8H7O

C, 100.00), 83(C4H3S

C, 16.20), 77 (C6H5C, 12.03).

3.1.18. 2-(4-Chlorophenyl)-5-phenyl-5-thien-2-yl-4,5-dihydrofuran-3-carbonitrile (3s). Yield 93% (675 mg) asa colourless solid, mp 122 8C (hexane/ EtOAc). [Found: C,69.5; H, 3.8; N, 3.9; S, 8.9. C21H14ClNOS requires C, 69.3;H, 3.9; N, 3.9; S, 8.8%]; nmax (KBr disc) 2200 (CN), 1623

(C]C), 829, 702; dH (400 MHz, CDCl3) 8.05 (2H, dt, JZ8.7, 1.9 Hz, arom.), 7.50–7.38 (7H, m, arom.), 7.35 (1H, dd,JZ3.6, 2.8 Hz, arom.), 7.0 (2H, dd, JZ2.7, 0.9 Hz, arom.),3.91 (1H, d, JZ15.0 Hz, Ha4), 3.73 (1H, d, JZ15.0 Hz,Hb4); dC (100 MHz, CDCl3) 164.2 (C2), 147.8, 143.5,137.9, 129.4, 128.9, 128.8, 128.7, 127.1, 126.7, 126.5,126.3, 125.5, 117.1 (CN), 91.1 (C3), 80.0 (C5), 47.2 (C4);m/z (EI, 70 eV) 364 (MHC, 11.35), 363 (MC, 19.80), 362(MCKH, 18.54), 328 (MCKCl, 6.21), 252 (MCKC6H5Cl,2.20), 224 (MCKC7H5ClO, 7.17), 139 (C7H5ClO

C,100.00), 111 (C6H5Cl

C, 43.70), 77 (C6H5C, 7.66).

Acknowledgements

The authors thanks to Ankara University Scientific ResearchProjects (BAP 20010705065), and the Scientific andTechnical Research Council of Turkey (TBAG-104T348)for financial supports. EIMS analyses were performed atScientific Research Center of Ankara University(BITAUM).

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