Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]([NH:10][C:11]2[CH:16]=[C:15]([CH2:17][OH:18])[CH:14]=[C:13]([NH:19][C:20]3[CH:25]=[N:24][CH:23]=[CH:22][N:21]=3)[N:12]=2)[CH3:9])=[CH:4][CH:3]=1.[C:26](Br)(Br)(Br)Br.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C[O-].[Na+].CO>C(Cl)Cl.C(OCC)(=O)C>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]([NH:10][C:11]2[CH:16]=[C:15]([CH2:17][O:18][CH3:26])[CH:14]=[C:13]([NH:19][C:20]3[CH:25]=[N:24][CH:23]=[CH:22][N:21]=3)[N:12]=2)[CH3:9])=[CH:4][CH:3]=1
Reactant: C[C@H](Nc1cc(CO)cc(Nc2cnccn2)n1)c1ccc(F)cc1
Reactant: BrC(Br)(Br)Br
Agent: C[O-]
Agent: [Na+]
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: ClCCl
Solvent: CCOC(C)=O
Solvent: CO
Product: COCc1cc(Nc2cnccn2)nc(N[C@@H](C)c2ccc(F)cc2)c1
Reaction time: 0.5 h
Yield: 33.6 %

Procedure:
20 mg of (S)-{2-[1-(4-fluorophenyl)ethylamino]-6-(pyrazin-2-ylamino)pyridin-4-yl}methanol (Example 140) was dissolved in methylene chloride, and 59 mg of carbon tetrabromide and 47 mg of triphenylphosphine were added under ice-cooling, and the mixture was stirred for 30 minutes. Subsequently, 90 μl of 9.8 M sodium methoxide/methanol solution was added thereto, and the mixture was stirred overnight. The reaction solution was diluted with ethyl acetate and was washed in turn with water and brine and then dried over magnesium sulfate. The solvent was distilled off under reduced pressure, and then the obtained residue was purified by silica gel column chromatography to obtain 7 mg of the objective compound as yellow powder.
Reaction SMILES: [C:1]1([S:7]([C:10]2[CH:15]=[CH:14][C:13](Br)=[CH:12][CH:11]=2)(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.O1CCCC1.N#N.C1(C)C=CC=CC=1.C([Li:35])CCC>CCCCCC>[C:1]1([S:7]([C:10]2[CH:15]=[CH:14][C:13]([Li:35])=[CH:12][CH:11]=2)(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: [Li]CCCC
Reactant: O=S(=O)(c1ccccc1)c1ccc(Br)cc1
Agent: N#N
Solvent: CCCCCC
Solvent: C1CCOC1
Solvent: Cc1ccccc1
Product: [Li]c1ccc(S(=O)(=O)c2ccccc2)cc1

Procedure:
A solution of 30 grams (0.1 mole) of 4-bromophenyl phenyl sulfone in 500 ml. of tetrahydrofuran was cooled to -100° C. in a liquid nitrogen-toluene slush, and 42 ml. (0.1 mole) of 2.38 M n-butyl lithium in hexane was added, forming 4-phenylsulfonyl-phenyl lithium. After about 10 minutes, 9.5 grams (0.05 mole) of diethyl dichlorophosphoramide was added, and the reaction mixture was allowed to warm slowly to room temperature, and then to stand a room temperature for 18 hours, forming diethyl bis [4-(phenylsulfonyl)phenyl] phosphoramide. Next, 125 ml. of 6 M HCl was added, and the reaction mixture was heated under reflux for 4 hours to hydrolyze the phosphoramide group. The tetrahydrofuran was removed by distillation, and 7.5 grams of almost white solid, M.P. 115°-130° C., was collected by filtration. This solid was recrystallized from tetrahydrofuran to give 7 grams (28% yield) of the bis[4-(phenylsulfonyl)phenyl] phosphinic acid product, m.p. 155°-165° C.
Reaction SMILES: Cl[C:2]1[N:7]=[C:6]([NH:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=2[S:15]([CH:18]([CH3:20])[CH3:19])(=[O:17])=[O:16])[C:5]([Cl:21])=[CH:4][N:3]=1.[CH3:22][P:23]([C:26]1[CH:32]=[CH:31][C:29]([NH2:30])=[C:28]([F:33])[CH:27]=1)([CH3:25])=[O:24].Cl.[OH-].[Na+]>COCCO.C(O)C>[Cl:21][C:5]1[C:6]([NH:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=2[S:15]([CH:18]([CH3:20])[CH3:19])(=[O:17])=[O:16])=[N:7][C:2]([NH:30][C:29]2[CH:31]=[CH:32][C:26]([P:23]([CH3:22])([CH3:25])=[O:24])=[CH:27][C:28]=2[F:33])=[N:3][CH:4]=1
Reactant: CC(C)S(=O)(=O)c1ccccc1Nc1nc(Cl)ncc1Cl
Reactant: CP(C)(=O)c1ccc(N)c(F)c1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Solvent: COCCO
Product: CC(C)S(=O)(=O)c1ccccc1Nc1nc(Nc2ccc(P(C)(C)=O)cc2F)ncc1Cl
Temperature: 90 °C
Yield: 15.1 %

Procedure:
To a solution of 2,5-dichloro-N-[2-(propan-2-ylsulfonyl)phenyl]pyrimidin-4-amine (as prepared in Example 17: 0.040 g, 0.12 mmol) in 1 mL of 2-methoxyethanol was added 4-(dimethylphosphoryl)-2-fluoroaniline (0.023 g, 0.12 mmol) and 49 μL of 2.5 M HCl in ethanol. The mixture was heated in a sealed tube at 90° C. for 16 h. The mixture was basified with 1N NaOH solution, and extracted with ethyl acetate. The organic layers were combined, washed with saturated sodium chloride solution, dried with sodium sulfate, filtered and concentrated. The crude residue was purified by prep-HPLC to afford the final compound (9.0 mg, 22% yield). MS/ES+: m/z=497.
Reaction SMILES: [H-].[Na+].[N+:3]([C:6]1[CH:11]=[CH:10][C:9]([C:12]23[CH2:18][CH:16]([CH2:17]2)[C:15](=[O:19])[NH:14][C:13]3=[O:20])=[CH:8][CH:7]=1)([O-:5])=[O:4].[CH2:21](I)[CH:22]([CH3:24])[CH3:23].C(OCC)(=O)C.CCCCCC>CN(C)C=O>[CH2:21]([N:14]1[C:15](=[O:19])[CH:16]2[CH2:17][C:12]([C:9]3[CH:8]=[CH:7][C:6]([N+:3]([O-:5])=[O:4])=[CH:11][CH:10]=3)([CH2:18]2)[C:13]1=[O:20])[CH:22]([CH3:24])[CH3:23]
Reactant: CC(C)CI
Reactant: O=C1NC(=O)C2(c3ccc([N+](=O)[O-])cc3)CC1C2
Agent: [H-]
Agent: [Na+]
Solvent: CCCCCC
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: CC(C)CN1C(=O)C2CC(c3ccc([N+](=O)[O-])cc3)(C2)C1=O
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
0.36 g of sodium hydride is added to a solution of 2.46 g of 1-(4-nitrophenyl)-3-azabicyclo[3.1.1]heptane-2,4-dione in 25 ml of N,N-dimethylformamide and the whole is stirred at room temperature for 30 minutes. 2.76 g of isobutyl iodide dissolved in 10 ml of N,N-dimethylformamide are then added dropwise thereto. When the reaction is complete, the reaction mixture is freed of N,N-dimethylformamide. The residue is partitioned between ethyl acetate and water, and the organic phase is dried over magnesium sulphate and, after concentration by evaporation and purification by chromatography over silica gel in the system ethyl acetate/hexane 1:2, the product is obtained in the form of a solid. Melting point 136°-137°. Rf (ethyl acetate/hexane 4:1)=0.6.
Reaction SMILES: CCCC[N+](CCCC)(CCCC)CCCC.[F-].[Si]([O:36][CH2:37][C@@H:38]1[CH2:43][CH:42]2[CH:40]([CH2:41]2)[N:39]1[C:44]([O:46][C:47]([CH3:50])([CH3:49])[CH3:48])=[O:45])(C(C)(C)C)(C1C=CC=CC=1)C1C=CC=CC=1.[NH4+].[Cl-]>C1COCC1>[OH:36][CH2:37][C@@H:38]1[CH2:43][CH:42]2[CH:40]([CH2:41]2)[N:39]1[C:44]([O:46][C:47]([CH3:50])([CH3:49])[CH3:48])=[O:45]
Reactant: CC(C)(C)OC(=O)N1C2CC2C[C@H]1CO[Si](c1ccccc1)(c1ccccc1)C(C)(C)C
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [Cl-]
Agent: [F-]
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)N1C2CC2C[C@H]1CO
Temperature: 25 °C
Reaction time: 4.75 h
Yield: 94 %

Procedure:
TBAF (7.27 mL of 1.0 M in THF, 7.27 mmol) was added dropwise over 5 min to a THF (30 mL) solution of (3S)-tert-butyl 3-((tert-butyldiphenylsilyloxy)methyl)-2-azabicyclo[3.1.0]hexane-2-carboxylate (mixture of cis/trans-isomers) (3.13 g, 6.93 mmol) and the mixture was stirred at ambient temperature for 4.75 h. After the addition of saturated NH4Cl solution (5 mL), most of the volatile material was removed in vacuo and the residue partitioned between CH2Cl2 (70 mL) and 50% saturated NH4Cl solution (30 mL). The aqueous phase was extracted with CH2Cl2 (30 mL) and the combined organic phase was dried (MgSO4), filtered, concentrated in vacuo and then exposed to high vacuum overnight. The crude material was purified using a flash chromatography (silica gel; 40-50% EtOAc/hexanes) to afford (3S)-tert-butyl 3-(hydroxymethyl)-2-azabicyclo[3.1.0]hexane-2-carboxylate (1.39 g, 94% yield) as a mixture of cis/trans-isomers and a colorless oil. [Note: the exact cis/trans-isomer ratio was not determined at this stage.] LC-MS (M+Na)+=236.20. 1H NMR (400 MHz, DMSO-d6, δ=2.5 ppm) δ ppm 4.70 (t, J=5.7, 1H), 3.62-3.56 (m, 1H), 3.49-3.44 (m, 1H), 3.33-3.27 (m, 1H), 3.08-3.04 (m, 1H), 2.07 (br m, 1H), 1.93-1.87 (m, 1H), 1.51-1.44 (m, 1H), 1.40 (s, 9H), 0.76-0.71 (m, 1H), 0.26 (m, 1H).
Reaction SMILES: [N+:1]([C:4]1[CH:44]=[CH:43][C:7]([C:8]([C:10]2[CH:15]=[CH:14][C:13]([C:16]3([C:26]4[CH:31]=[CH:30][C:29]([C:32](=O)[C:33]5[CH:38]=[CH:37][C:36]([N+:39]([O-:41])=[O:40])=[CH:35][CH:34]=5)=[CH:28][CH:27]=4)[CH2:21][CH2:20][CH:19]([CH2:22][CH2:23][CH2:24][CH3:25])[CH2:18][CH2:17]3)=[CH:12][CH:11]=2)=O)=[CH:6][CH:5]=1)([O-:3])=[O:2].C([SiH](CC)CC)C>ClCCl>[N+:1]([C:4]1[CH:5]=[CH:6][C:7]([CH2:8][C:10]2[CH:15]=[CH:14][C:13]([C:16]3([C:26]4[CH:31]=[CH:30][C:29]([CH2:32][C:33]5[CH:34]=[CH:35][C:36]([N+:39]([O-:41])=[O:40])=[CH:37][CH:38]=5)=[CH:28][CH:27]=4)[CH2:21][CH2:20][CH:19]([CH2:22][CH2:23][CH2:24][CH3:25])[CH2:18][CH2:17]3)=[CH:12][CH:11]=2)=[CH:43][CH:44]=1)([O-:3])=[O:2]
Reactant: CCCCC1CCC(c2ccc(C(=O)c3ccc([N+](=O)[O-])cc3)cc2)(c2ccc(C(=O)c3ccc([N+](=O)[O-])cc3)cc2)CC1
Agent: CC[SiH](CC)CC
Solvent: ClCCl
Product: CCCCC1CCC(c2ccc(Cc3ccc([N+](=O)[O-])cc3)cc2)(c2ccc(Cc3ccc([N+](=O)[O-])cc3)cc2)CC1
Temperature: 25 °C
Reaction time: 5 h
Yield: 87.9 %

Procedure:
1,1-Bis[4-(4-nitrobenzoyl)phenyl]-4-butylcyclohexane 45.40 g was dissolved in dichloromethane 660 ml, and a solution of trifluorosulfuric acid 36.9 g in dichloromethane 860 ml was added dropwise for one hour. Then, a solution of triethylsilane 47.38 g in dichloromethane 80 ml was added dropwise for 90 minutes. When 30 minutes passed after the addition was finished, the ice bath was removed and the solution was stirred for five hours at room temperature. The finish of the reaction was confirmed by liquid chromatography, and then the reaction solution was neutralized with an aqueous solution of sodium carbonate and washed with water. After dichloromethane was removed with a rotary evaporator, the residue was dissolved in toluene, the solution was treated with an alumina column, and the solvent was distilled away from the elute to obtain 1,1-bis[4-(4-nitrobenzyl)phenyl]-4-butylcyclohexane 38.0 g.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][C:5]([OH:24])=[C:6]([C:8]2[C:17]([CH2:18][OH:19])=[C:16]3[C:11]([NH:12][C:13]([CH3:23])([CH3:22])[C:14](=[O:21])[N:15]3[CH3:20])=[CH:10][CH:9]=2)[CH:7]=1.CI.[C:27](=O)([O-])[O-].[K+].[K+].C(OCC)(=O)C>CN(C)C=O.O.C(OCC)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:24][CH3:27])=[C:6]([C:8]2[C:17]([CH2:18][OH:19])=[C:16]3[C:11]([NH:12][C:13]([CH3:22])([CH3:23])[C:14](=[O:21])[N:15]3[CH3:20])=[CH:10][CH:9]=2)[CH:7]=1
Reactant: CN1C(=O)C(C)(C)Nc2ccc(-c3cc(Cl)ccc3O)c(CO)c21
Reactant: O=C([O-])[O-]
Agent: [K+]
Solvent: CCOCC
Solvent: CI
Solvent: CCOC(C)=O
Product: COc1ccc(Cl)cc1-c1ccc2c(c1CO)N(C)C(=O)C(C)(C)N2
Temperature: 50 °C
Reaction time: 1 h
Yield: 96.1 %

Procedure:
A mixture of 7-(5-chloro-2-hydroxyphenyl)-8-hydroxymethyl-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one (Reference Compound No. 12-1, 1.36 g, 3.92 mmol), methyl iodide (244 μL, 3.92 mmol), and potassium carbonate (1.08 g, 7.81 mmol) was suspended in anhydrous N,N-dimethylformamide (20 mL) and stirred at 50° C. for 1 hour. After cooling down, ethyl acetate (70 mL), diethylether (70 mL), and water (150 mL) were added and partitioned. The organic layer was washed with water (100 mL) and saturated brine (50 mL) successively, dried over anhydrous magnesium sulfate, and then the solvent was removed under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane-ethyl acetate) to give the titled reference compound (1.36 g) as a pale yellow amorphous product. (Yield 96%)
Reaction SMILES: [CH3:1][O:2][C:3]1[C:8]([O:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[O:16][CH3:17])=[C:7]([NH:18][S:19]([C:22]2[CH:27]=[CH:26][C:25]([CH3:28])=[CH:24][N:23]=2)(=[O:21])=[O:20])[N:6]=[C:5]([C:29]2[CH:34]=[CH:33][N:32]=[C:31]([C:35]([OH:37])=[O:36])[CH:30]=2)[N:4]=1.[C:38](=[O:50])([O:46][CH:47](Cl)[CH3:48])[O:39][CH:40]1[CH2:45][CH2:44][CH2:43][CH2:42][CH2:41]1>>[CH:40]1([O:39][C:38]([O:46][CH:47]([O:36][C:35]([C:31]2[CH:30]=[C:29]([C:5]3[N:4]=[C:3]([O:2][CH3:1])[C:8]([O:9][C:10]4[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=4[O:16][CH3:17])=[C:7]([NH:18][S:19]([C:22]4[CH:27]=[CH:26][C:25]([CH3:28])=[CH:24][N:23]=4)(=[O:21])=[O:20])[N:6]=3)[CH:34]=[CH:33][N:32]=2)=[O:37])[CH3:48])=[O:50])[CH2:45][CH2:44][CH2:43][CH2:42][CH2:41]1
Reactant: COc1ccccc1Oc1c(NS(=O)(=O)c2ccc(C)cn2)nc(-c2ccnc(C(=O)O)c2)nc1OC
Reactant: CC(Cl)OC(=O)OC1CCCCC1
Product: COc1ccccc1Oc1c(NS(=O)(=O)c2ccc(C)cn2)nc(-c2ccnc(C(=O)OC(C)OC(=O)OC3CCCCC3)c2)nc1OC

Procedure:
In analogy to example 77, from 4-[4-methoxy-5-(2-methoxy-phenoxy)-6-(5-methyl-pyridine-2-sulfonylamino)-pyrimidin-2-yl]-pyridine-2-carboxylic acid, product of example 21, and cyclohexyl 1-chlorethyl carbonate (synthesis described by A. Riondel et al., Tetrahedron, 1988, Vol. 44, 1619) there was obtained 4-[4-methoxy-5-(2-methoxy-phenoxy)-6-(5-methyl-pyridine-2-sulfonylamino)-pyrimidin-2-yl]-pyridine-2-carboxylic acid 1-cyclohexyloxycarbonyloxy-ethyl ester as a white solid. ISN mass spectrum, m/e 692.1 (M−1 calculated for C33H35N5O10S: 692).
Reaction SMILES: [N:1]1([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH:5]2[CH2:6][NH:7][CH2:8][CH2:9][CH:4]2[CH2:3][CH2:2]1.C([O-])([O-])=O.[K+].[K+].Br[CH2:24][CH2:25][CH2:26][Cl:27]>CC(C)=O.O>[C:13]([O:12][C:10]([N:1]1[CH:5]2[CH2:6][N:7]([CH2:24][CH2:25][CH2:26][Cl:27])[CH2:8][CH2:9][CH:4]2[CH2:3][CH2:2]1)=[O:11])([CH3:16])([CH3:15])[CH3:14]
Reactant: CC(C)(C)OC(=O)N1CCC2CCNCC21
Reactant: ClCCCBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Solvent: O
Product: CC(C)(C)OC(=O)N1CCC2CCN(CCCCl)CC21
Yield: 75 %

Procedure:
To a solution of tert-butyl octahydro-1H-pyrrolo[2,3-c]pyridine-1-carboxylate (1.21 g) in acetone (15 mL) was added K2CO3 (3.00 g) and 1-bromo-3-chloropropane (1.6 mL). The reaction mixture was heated to reflux for 7 h, diluted with water and extracted with EtOAc. The organic layer was dried over anhydrous Na2SO4 for 1 h and filtered. The filtrate was concentrated in vacuo and the residue was chromatographed with a silica gel column (eluting agent: 30:1 (v/v) CH2Cl2/MeOH) to afford the title compound as pale yellow liquid (1.20 g, 75.00%).
Reaction SMILES: [N:1]1([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[C:9]2[CH:8]=[CH:7][CH:6]=[C:5]([C:10]([O:12]CC3C=CC=CC=3)=[O:11])[C:4]=2[CH:3]=[CH:2]1.[H][H]>[Pd].CO.O>[C:23]([O:22][C:20]([N:1]1[C:9]2[CH:8]=[CH:7][CH:6]=[C:5]([C:10]([OH:12])=[O:11])[C:4]=2[CH:3]=[CH:2]1)=[O:21])([CH3:26])([CH3:24])[CH3:25]
Reactant: [H][H]
Reactant: CC(C)(C)OC(=O)n1ccc2c(C(=O)OCc3ccccc3)cccc21
Agent: [Pd]
Solvent: O
Solvent: CO
Product: CC(C)(C)OC(=O)n1ccc2c(C(=O)O)cccc21
Yield: 61.2 %

Procedure:
The mixture of 4-benzyl 1-tert-butyl 1H-indole-1,4-dicarboxylate (6.37 g) and 10% palladium on carbon (964 mg) in MeOH (95.6 mL) and water (3.2 mL) was hydrogenated at 3.5 atm of hydrogen for 3.5 hours. The resulting mixture was filtered through a bed of celite and the filtrate was evaporated in vacuo. The residue was dissolved in chloroform (100 mL) and the solution was dried over anhydrous MgSO4, filtered and evaporated in vacuo. The residue was triturated with cold MeOH (20 mL) to give 1-(tert-butoxycarbonyl)-1H-indole-4-carboxylic acid (2.90 g) as a colorless crystals. The above filtrate was evaporated in vacuo and the residue was triturated with solvent (n-hexane:EtOAc=5:1, 12 mL) to afford 1-(tert-butoxycarbonyl)-1H-indole-4-carboxylic acid (1.31 g) as colorless crystals.
Reaction SMILES: CC1[C:6](=O)[O:5][C@@H:4]([O:8]/C=C2\[C@@H]3[C@H](OC\2=O)C2C(C)(C)CC[C@H](O)C=2C3)[CH:3]=1.[CH3:26][C:27]1[C:32](=[O:33])[CH2:31][CH2:30][C:29]([CH3:35])([CH3:34])[C:28]=1[C:36]([OH:38])=O.[Na]C(C(OC)=O)C(OC)=O>>[O:38]=[C:36]1[C:28]2[C:29]([CH3:34])([CH3:35])[CH2:30][CH2:31][C:32](=[O:33])[C:27]=2[CH2:26][CH:3]1[C:4]([O:5][CH3:6])=[O:8]
Reactant: CC1=C(C(=O)O)C(C)(C)CCC1=O
Reactant: CC1=C[C@H](O/C=C2/C(=O)O[C@@H]3C4=C(C[C@H]23)[C@@H](O)CCC4(C)C)OC1=O
Agent: COC(=O)C([Na])C(=O)OC
Product: COC(=O)C1CC2=C(C1=O)C(C)(C)CCC2=O

Procedure:
A process for preparing dl-strigol, a potent seed germination agent, which comprises preparing the 2-bromomethyl-substituted methyl ester of 2,6,6-trimethylcyclohex-1-en-3-one-1-carboxylic acid, alkylating and cyclizing the said compound with an excess of dimethyl sodiomalonate to obtain methyl 1,4-diketo-7,7-dimethyl-4,5,6,7-tetrahydroindane-2-carboxylate and its enol, subjecting the said keto and enol forms of the compound, in admixture, to alkylation with methyl bromoacetate followed by acidic hydrolysis and spontaneous decarboxylation to obtain methyl 1,4-diketo-7,7-dimethyl-4,5,6,7-tetrahydroindane-2-acetic acid, reducing the said acetic acid with a hydride reducing agent and recovering and separating the resulting 1,4-cis and trans-dihydroxy-7,7-dimethyl-4,5,6,7-tetrahydroindane-2-acetic acid lactones, formylating each of the cis and trans γ lactones, alkylating the respective resulting hydroxy methylene lactones with bromobutenolide and recovering dl-strigol, dl-4'-epi-strigol, dl-4-epi-strigol and dl-4,4'-diepi-strigol.
Reaction SMILES: [O:1]=[C:2]([CH3:8])[CH2:3][CH2:4][CH2:5][C:6]#[N:7].[Cl-].[Ce+3].[Cl-].[Cl-].[CH:13]1([Mg]Cl)[CH2:17][CH2:16][CH2:15][CH2:14]1.Cl>C1COCC1>[CH:13]1([C:2]([OH:1])([CH3:8])[CH2:3][CH2:4][CH2:5][C:6]#[N:7])[CH2:17][CH2:16][CH2:15][CH2:14]1
Reactant: CC(=O)CCCC#N
Reactant: Cl[Mg]C1CCCC1
Agent: Cl
Agent: [Ce+3]
Agent: [Cl-]
Solvent: C1CCOC1
Product: CC(O)(CCCC#N)C1CCCC1
Temperature: 25 °C
Reaction time: 1 h
Yield: 60 %

Procedure:
5-Oxohexanenitrile (11.1 g; 0.10 mmol) was added at 20° C. to a suspension of anhydrous cerium(III) chloride (30 g; 0.12 mol) in THF (250 ml). After 1 hour stirring at room temperature, cyclopentylmagnesium chloride (60 ml of 2.0 M solution in diethyl ether; 0.12 mol) was added dropwise at 5° C. and stirring continued for more 0.5 hour at the same temperature. 2 N HCl (60 ml) was added, and the reaction mixture was extracted with MTBE (2×200 ml). The combined organic phases were washed with 2 N HCl (100 ml), and brine (2×100 ml), dried (MgSO4), and concentrated in vacuo, to give 13 g of crude (83% GC pure; 60% yield) 5-cyclopentyl-5-hydroxyhexanenitrile. The 5-cyclopentyl-5-hydroxyhexanenitrile was used without further purification in the next step.
Reaction SMILES: [Cl-].[Al+3].[Cl-].[Cl-].[CH3:5][C:6]1([CH3:16])[C:14]2[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=2)[NH:8][C:7]1=[O:15].[Cl:17][CH2:18][C:19](Cl)=[O:20].Cl>CN(C=O)C>[Cl:17][CH2:18][C:19]([C:12]1[CH:13]=[C:14]2[C:9](=[CH:10][CH:11]=1)[NH:8][C:7](=[O:15])[C:6]2([CH3:16])[CH3:5])=[O:20]
Reactant: CC1(C)C(=O)Nc2ccccc21
Reactant: O=C(Cl)CCl
Agent: Cl
Agent: [Al+3]
Agent: [Cl-]
Solvent: CN(C)C=O
Product: CC1(C)C(=O)Nc2ccc(C(=O)CCl)cc21
Temperature: 70 °C
Reaction time: 0.25 h

Procedure:
13.3 g aluminium chloride and 2.2 ml DMF were mixed and heated with stirring, at 70° C. during 15 min. After cooling to 40° C., 1.5 g 1,3-dihydro-3,3-dimethyl-2H-indol-2-one and 1.1 g 2-chloroacetyl chloride were added and stirred at 70° C. for 45 min. The mixture was poured onto 50 g ice and 10 ml 10N HCl and extracted with 3×75 ml ethyl acetate.
Reaction SMILES: [NH2:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[CH:4]=[CH:5][NH:6]2.[Br:11][C:12]1[CH:17]=[CH:16][C:15]([CH2:18][N:19]=[C:20]=[O:21])=[CH:14][CH:13]=1.CCCCCC>C1COCC1>[Br:11][C:12]1[CH:13]=[CH:14][C:15]([CH2:18][NH:19][C:20]([NH:1][C:2]2[CH:10]=[CH:9][CH:8]=[C:7]3[C:3]=2[CH:4]=[CH:5][NH:6]3)=[O:21])=[CH:16][CH:17]=1
Reactant: Nc1cccc2[nH]ccc12
Reactant: O=C=NCc1ccc(Br)cc1
Solvent: CCCCCC
Solvent: C1CCOC1
Product: O=C(NCc1ccc(Br)cc1)Nc1cccc2[nH]ccc12

Procedure:
4-aminoindole (0.13 g, 1 mmol) in THF (3 mL) was treated with 1-bromo-4-(isocyanatomethyl)benzene (0.23 g, 1.1 mmol) for 3 hours at ambient temperature. Hexane was added to the reaction mixture to precipitate 0.26 g of the title compound as a tan solid. mp 198° C.; 1H NMR (300 MHz, DMSO-d6) δ 4.30 (d, 2H), 6.51 (t, 1H), 6.89 (t, 1H), 6.95 (d, 2H), 7.29 (t, 1H), 7.31 (d, 2H), 7.55 (d, 2H), 7.62 (dd, 1H), 8.3 (s, 1H), 11.04 (s, 1H); MS (DCI+) m/z 346 (M+H); Anal. Calcd. For C16H14N3BrO: C, 55.83; H, 4.10; N, 12.21. Found: C, 55.71; H, 4.12; N, 12.01.
Reaction SMILES: [CH3:1][Mg]Br.[OH:4][C:5]1[CH:10]=[CH:9][C:8]([O:11][CH3:12])=[CH:7][C:6]=1[C:13](=[O:15])[CH3:14]>C1COCC1>[OH:15][C:13]([C:6]1[CH:7]=[C:8]([O:11][CH3:12])[CH:9]=[CH:10][C:5]=1[OH:4])([CH3:1])[CH3:14]
Reactant: C[Mg]Br
Reactant: COc1ccc(O)c(C(C)=O)c1
Solvent: C1CCOC1
Product: COc1ccc(O)c(C(C)(C)O)c1
Temperature: 25 °C
Yield: 91.9 %

Procedure:
To a solution of methylmagnesium bromide (221 ml, 665 mmol) in 800 ml THF at 0° C. was added 1-(2-hydroxy-5-methoxy-phenyl)-ethanone (20.21 g, 302 mmol) in portions over 30 min. The mixture was allowed to warm to room temperature. After 16 h the mixture was quenched by the slow addition of 10% NH4Cl, carefully acidified to pH=1 (slow addition) with concentrated HCl and extracted with Et2O. The combined organics were washed with H2O, washed with brine, died over MgSO4, filtered and concentrated in vacuo to give 2-(1-hydroxy-1-methyl-ethyl)-4-methoxy-phenol (50.57 g, 100%) as a tan solid.
Reaction SMILES: [CH3:1][O:2][CH:3]([CH2:6][O:7][C:8]([C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)([C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)[CH2:4][OH:5].C(N(CC)CC)C.[C:34]1([CH3:44])[CH:39]=[CH:38][C:37]([S:40](Cl)(=[O:42])=[O:41])=[CH:36][CH:35]=1.Cl>C(Cl)Cl>[CH3:1][O:2][CH:3]([CH2:4][O:5][S:40]([C:37]1[CH:38]=[CH:39][C:34]([CH3:44])=[CH:35][CH:36]=1)(=[O:42])=[O:41])[CH2:6][O:7][C:8]([C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)([C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=1)[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1
Reactant: COC(CO)COC(c1ccccc1)(c1ccccc1)c1ccccc1
Reactant: Cc1ccc(S(=O)(=O)Cl)cc1
Agent: Cl
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: COC(COC(c1ccccc1)(c1ccccc1)c1ccccc1)COS(=O)(=O)c1ccc(C)cc1
Temperature: 25 °C
Reaction time: 17 h
Yield: 89.4 %

Procedure:
In 40 ml of methylene chloride were dissolved 3.484 g (10 mmole) of the alcohol derivative as synthesized in (i) and 3.036 g (30 mmole) of triethylamine, and 2.478 g (13 mmole) of p-toluenesulfonyl chloride was added to the solution under ice-cooling. The reaction solution was stirred at room temperature for 17 hours, treated with 1N hydrochloric acid and extracted with chloroform. The organic layer was dried over magnesium sulfate and the solvent was distilled off under reduced pressure. The resulting crude product was purified by column chromatography [silica gel: 170 g; eluent: n-hexane/ethyl acetate=5/1 to 3/1] to give 4.491 g (89.4%) of the objective compound as a colorless solid.
Reaction SMILES: [O:1]1[CH:5]=[CH:4][CH:3]=[CH:2]1.C([Li])CCC.[CH3:11][O:12][CH2:13][CH2:14][O:15][CH2:16]Cl>C1COCC1>[CH3:11][O:12][CH2:13][CH2:14][O:15][C:16]1[CH:3]=[CH:2][O:1][C:5]=1[CH3:4]
Reactant: COCCOCCl
Reactant: c1ccoc1
Agent: [Li]CCCC
Solvent: C1CCOC1
Product: COCCOc1ccoc1C
Temperature: -78 °C
Reaction time: 3 h
Yield: 63.2 %

Procedure:
To a solution of furan (10.7 mL, 0.147 mol) in 100 mL of THF at 0° C. was added n-butyllithium (65 mL, 0.149 mol). The reaction was stirred 3 h and was cooled to -78° C. To the reaction flask was then slowly added 2-methoxy-ethoxymethylchloride (16.8 mL, 0.147 mol) in 100 mL THF. The solution was warmed to -20° C. and allowed to stir until the solution was clear. It was then quenched with saturated ammonium chloride solution (50mL) and the aqueous layer was washed with ethyl acetate (3×, 50 mL). The combined organic layer was washed with brine, dried (MgSO4), filtered and evaporated to yield 18 g of crude product. Distillation under high vacuum yielded 14.5 g (63%) of 2-methoxyethoxy-methylfuran.