Cross-Coupling of Aromatic Bromides with Allylic Silanolate Salts

Transcription

1 S1 Cross-Coupling of Aromatic Bromides with Allylic Silanolate Salts Scott E. Denmark* and Nathan S. Werner Roger Adams Laboratory, University of Illinois, 600 S. Mathews Avenue, Urbana, Illinois 6101 SUPPORTING INFORMATION Table of Contents General Experimental Response Factors Literature Preparations Experimental Procedures General Cross-Coupling Procedures Allylation Procedures Crotylation Procedures References Page S1 S S5 S5 S1 S1 S1 S56 1 H NMR Spectra S5 General Experimental All reactions were performed in oven (10 o C) and /or flame dried glassware under an atmosphere of dry argon unless otherwise noted. Reaction solvents tetrahydrofuran (Fisher, HPLC grade), ether (Fisher, BHT stabilized ACS grade) and methylene chloride (Fisher, unstabilized HPLC grade) were dried by percolation through two columns packed with neutral alumina under a positive pressure of argon. Reaction solvents hexanes (Fisher, OPTIMA grade) and toluene (Fisher, ACS grade were dried by percolation through a column packed with neutral alumina and a column packed with Q5 reactant, a supported copper catalyst for scavenging oxygen, under a positive pressure of argon. Reaction solvents dioxane and benzene were

2 S2 distilled from sodium, acetonitrile was distilled from CaH 2, and dimethoxyethane (DME) was distilled from sodium benzophenone ketyl prior to use. Solvents for filtration and chromatography were certified ACS grade. Brine refers to a saturated solution of sodium chloride in water. All reaction temperatures correspond to internal temperatures measured with Teflon coated thermocouples. 1 H and 1 C NMR spectra were recorded on a Varian Unity-500 MHz (126 MHz, 1 C) spectrometer. Spectra are referenced to residual chloroform (δ =.26 ppm, 1 H;.0 ppm, 1 C) or residual benzene (δ =.15 ppm, 1 H; 12.0 ppm, 1 C). Chemical shifts are reported in ppm, multiplicities are indicated by s (singlet), d (doublet), t (triplet), q (quartet), p (pentet), h (hextet), m (multiplet) and br (broad). Coupling constants, J, are reported in Hertz, and integration is provided and assignments are indicated. Mass Spectrometry (MS) was performed by the University of Illinois Mass Spectrometer Center. Electron Impact (EI) spectra were performed at 0 ev using methane as the carrier gas on a Finnegan-MAT C5 spectrometer. Data are reported in the form of m/z (intensity relative to the base peak = 100). Infrared spectra (IR) spectra were recorded on a Perkin-Elmer FT-IR system and peaks are reported in cm -1 with indicated relative intensities: s (strong, 0-% T); m (medium, -66% T), w (weak, 6-100% T). lting points (mp) were determined on a Thomas-Hoover capillary melting point apparatus in sealed tubes and are corrected. Kugelrohr (bulb-to-bulb) distillations were performed on a Büchi GKR-50 apparatus with boiling points (bp) corresponding to uncorrected air bath temperatures (ABT). Analytical gas chromatography (GC) was performed using a Hewlett-Packard 590 Gas Chromatograph fitted with a flame ionization detector. Three GC thods were used. GC thod 1 involved injections onto a Hewlett-Packard HP1 (0 m x 0.2 mm) capillary column. Injector temperature was 250 o C and the detector temperature was 00 o C with a H 2 carrier gas

3 S flow of 16 ml/min. The column temperature program was as follows: 15 o C for 5 min, 15 o C to 250 o C at 10 o C/min, then hold for min for a total run time of 1 min. GC thod 2 involved injections onto a Hewlett-Packard HP1MS (0m x 0.2 mm) capillary column. Injector temperature was 250 o C and the detector temperature was 00 o C with a H 2 carrier gas flow of 16 ml/min. The column temperature program was as follows: 100 o C for min, 100 o C to 260 o C at 0 o C/min, then hold for min for a total run time of 1 min. GC thod involved injections onto a Hewlett-Packard HP1 (0m x 0.2 mm) capillary column. Injector temperature was 250 o C and the detector temperature was 00 o C with a H 2 carrier gas flow of 16 ml/min. The column temperature program was as follows: 100 o C for min, 100 o C to 260 o C at 0 o C/min, then hold for min for a total run time of 1 min. Retention times (t R ) were obtained using Agilent Chemstation software. Response factors were generated by triplicate runs of three molar ratios of compound and biphenyl dissolved in ethyl acetate. Commercial reagents were purified by distillation or recrystallization prior to use unless noted. 1-Bromonaphthalene, -bromobenzotrifluoride, -bromobenzophenone, and 2-bromo-6- methoxynaphthalene were purchased from Alfa Aesar. -Bromoanisole, -bromo-n,ndimethylaniline, -bromobenzoyl chloride, -bromochlorobenzene, -bromobenzonitrile, 2- bromonaphthalene, 2-bromoanisole, 2-bromo-N,N-dimethylaniline, 5-bromo-m-xylene, - bromobenzyl alcohol, trichlorosilane, crotyl chloride, cyclooctadiene, 1,-benzoquinone, norbornadiene, maleic anhydride, and tetramethylethylene were purchased from Aldrich.,5- bis(trifluoromethyl)bromobenzene was purchased from Matrix Scientific. Triphenylphosphine, 2-(di-t-butylphosphino)biphenyl, triphenylphosphine oxide, (t-bu P) 2 Pd, 6-bromoindole, - bromophenol, triphenylarsine, Li (titrated at 1. M in ether), diallylcarbonate, (o-tol) P, 1,- bis(diphenylphosphino)propane, 1,1 bis(diphenylphosphino)ferrocene, BINAP, palladium

4 S acetate, palladium bromide and dicyclopentadiene were purchased from Aldrich and used as received. Allyldimethylchlorosilane was purchased from Gelest. trans, trans- Dibenzylideneacetone was purchased from Acros and used as received. Tricyclohexylphosphine, Josiphos, and allylchloro[1,-bis(2,6-di-i-propylphenyl)imidazol-2- ylidene]palladium(ii) were purchased from Strem and used as received. Palladium chloride was purchased from Pressure Chemical and used as received. Sodium hydride and potassium hydride were purchased from Aldrich as a suspension in mineral oil, washed with hexanes and stored under dry argon. Response Factors Response factors for quantitative GC analysis using GC thod were calculated using the following equation and data: Response factor = (mmol compound * rel. area biphenyl)/(mmol biphenyl * rel. area compound) mmol biphenyl Rel. Area biphenyl mmol 1- bromonaphthalene Rel. Area 1- bromonaphthalene Response Factor Avg: 1.20 mmol biphenyl Rel. Area biphenyl mmol γ-1h Rel. Area γ-1h Response Factor Avg: 0.95

5 S5 Literature Preparations The following compounds were prepared by literature methods: allylpalladium chloride dimer (APC), 1 Pd(dba) 2, 2 Pd 2 dba, 2 -allylbenzophenone, 2-butenyltrichlorosilane,,- dimethylcyclohexa-2,5-diene-1-one, 5 2-propenyldimethylchlorosilane, 6 2- butenyldimethylchlorosilane, diallyl ether, diphenylphosphino-2,6 -dimethyoxybiphenyl, 9 diphenylphosphino-2 6 -triisopropylbiphenyl, 10 6-bromo-N-Boc-indole, 11 - bromotriethylsilylbenyl ether, 12 tert-butyl -bromobenzoate, 1 -bromophenyldimethyl(tertbutyl)silyl ether, 1 (E)-2-butynol, 15 (E)-1-chloro-2-butene, 16 (Z)-2-butenyltrichlorosilane, bis(- methoxybenzylidene)acetone, 1 and bis(-trifluoromethylbenzylidene)acetone). Preparation of 1,1-Dimethyl-1-(2-propen-1-yl)silanol (1) Si Cl 1M acetate buffer ph = 5 ether, rt 6 1 1' 1' 2 Si OH To a single-necked, 1-L, round-bottomed flask equipped with a magnetic stir bar was added 29 ml of 1 M acetate buffer (ph = 5) and ether ( ml). Allyldimethylchlorosilane (.5 g, 65.0 mmol) was then dissolved in ether ( ml) then added by pipette to the vigorously stirring, heterogeneous mixture of acetate buffer and ether. After being stirred for 5 min, the reaction mixture was then poured into a 1-L separatory funnel and diluted with ether (0 ml). The aqueous phase was separated and washed with ether (2 x 0 ml). The three separate organic extracts were then sequentially washed with sat. aq. NaHCO (20 ml) and the ph of the resulting aqueous wash was checked with litmus paper to ensure alkalinity. The organic extracts were then washed with brine, combined, and dried over Na 2 SO, and then filtered through a pad 1

6 S6 of silica gel (5 g) in a glass-fritted funnel (coarse, 5 cm x cm). The filtrate was concentrated (ambient temp., 20 mm Hg) and the residue purified by column chromatography (SiO 2, 0 mm x 20 cm, pentane/et 2 O, :1), followed by simple distillation to provide 6. g (90%) of 1 as a clear, colorless oil. Data for (1): bp: 1 C (60 mmhg) 1 H NMR: (500 MHz, CDCl ) 5.2 (ddt, J = 16.9, 10.1,.1, 1 H, HC(2)),.91 (m, 2 H, HC()), 1.1 (b, 1 H, HO), 1.6 (d, J =.1, 2 H, HC(1)), 0.16 (s, 6 H, HC(1 )). 1 C NMR: (126 MHz, CDCl ) 1. C(2), 11.9 C(), 25.9 C(1), C(1 ). IR: (film) 29 (s), 00 (m), 062 (w), 299 (w), 2960 (m), 1916 (w), 26 (w), 162 (m), 120 (w), 19 (w), 1256 (s), 1192 (w), 1160 (m), 106 (m), 10 (m), 992 (m), 92 (m), 95 (s), 6 (s), (s), 5 (m), 22 (w), 69 (w), 65 (m), 6 (m). MS: (EI, 0 ev) 1 (6), 19 (6), 1 (6), 116 (M +, 5), 101 (9), 5 (100), 61 (10). TLC: R f 0.19 (pentane/et 2 O, :1) [silica gel, aqueous KMnO ]

7 S Preparation of Sodium 1,1-Dimethyl-1-(2-propen-1-yl)silanolate (Na ) Si OH NaH THF, rt 1' 1' 2 Si O - Na + 1 Na In a dry box, washed NaH (61 mg, 25. mmol, 1.1 equiv) and THF (1 ml) were combined in a 50-mL, single-necked, round-bottomed flask containing a magnetic stir bar. In a separate 50-mL, single-necked, round-bottomed flask containing allyldimethylsilanol (2.2 g, 2. mmol) was added THF (2 ml), this solution was then mixed and added drop-wise over 10 min to the stirred suspension of NaH. After being stirred for 0 min, the resulting mixture was filtered through a glass-fritted filter (medium,.5 cm x.5 cm) into a 25-mL Schlenk flask. The filtrate was concentrated (ambient temp., 20 mm Hg) to afford a colorless amorphous solid. Hexane (10 ml) was then added and the resulting solution was concentrated (ambient temp., 0.5 mm Hg) to afford 2.2 g (9%) of Na as a white powder. Data for (Na ): 1 H NMR: (500 MHz, C 6 D 6 ) 6.11 (ddt, J = 1.1, 10.0,., 1 H, HC(2)),.9 (m, 2 H, HC()), 1.5 (d, J =., 2 H, HC(1)), 0.0 (s, 6 H, HC(1 )). 1 C NMR: (126 MHz, C 6 D 6 ) 11.2 C(2), C(), 0.5 C(1),.2 C(1 ). Analysis: C 5 H 11 NaOSi (1.22) Calcd: C,.5; H,.02 Found: C,.06; H,.21 1

8 S Preparation of 1,1-Dimethyl-1-(2-buten-1-yl)silanol (1) Si Cl acetate buffer ph = 5 ether, rt 12 1 Si OH To a single-necked, 1-L, round-bottom flask equipped with a magnetic stir bar was added 99 ml of 1 M acetate buffer (ph = 5) and ether (0 ml). 2-butenyldimethylchlorosilane (10.0 g, 60.5 mmol) was then dissolved in ether (0 ml) then added by pipette to the vigorously stirring, heterogeneous mixture of acetate buffer and ether. After being stirred for 5 min, the reaction mixture was then poured into a 1-L separatory funnel and diluted with ether (50 ml). The aqueous phase was separated and washed with ether (2 x 50 ml), The three separate organic extracts were then sequentially washed with sat. aq. NaHCO (50 ml) and the ph of the resulting aqueous wash was checked with litmus paper to ensure alkalinity. The organic extracts were then washed with brine (50 ml), combined, dried over Na 2 SO, and then filtered through a pad of silica gel (10 g). The filtrate was concentrated (ambient temp., 20 mm Hg) and the residue purified by column chromatography (SiO 2, 0 mm x 20 cm, pentane/et 2 O, :1). Fractions were combined, concentrated to ~20 ml (ambient temp., 20 mm Hg) and then was transferred to a dry box for conversion to its sodium salt. Data for (1): bp: 19 C (60 mmhg) TLC: R f 0.2 (pentane/et 2 O, :1) [silica gel, aqueous KMnO ]

9 S9 Preparation of Sodium 1,1-Dimethyl-1-(2-buten-1-yl)silanolate (Na ) Si OH NaH THF, rt 2 1' 1' Si O - Na Na In a dry box, washed NaH (1. g, 6.6 mmol, 1.1 equiv) and THF (20 ml) were combined in a 50-mL, single-neck, round-bottomed flask containing a magnetic stir bar. In a separate 50-mL, single-neck, round-bottomed flask containing 2-butenyldimethylsilanol (69.6 mmol) was added THF (10 ml), this solution was then mixed and added drop-wise over 10 min to the stirred suspension of NaH. After being stirred for 0 min, the resulting mixture was filtered through a glass-fritted filter (medium,.5 cm x.5 cm) into a 100-mL Schlenk flask. The filtrate was concentrated (ambient temp., 20 mm Hg) to afford a colorless amorphous solid. Hexane (10 ml) was then added and the resulting solution was concentrated (ambient temp., 0.5 mm Hg) to afford.5 g (1%) of Na as a white powder. Data for (Na ): 1 H NMR: (500 MHz, C 6 D 6 ) 5.0 (m, 1 H, HC(2)), 5.2 (m, 1 H, HC()), 1.2 (dd, J = 6., 0.9, H, HC()), 1.52 (d, J =.9, 2 H, HC(1)), 0.1 (s, 6 H, HC(1 )). 1 C NMR: (126 MHz, C 6 D 6 ) 11. C(2), C(), 2. C(1), 1.2 C(),.1 (C(1 ).

10 S10 Preparation of (E)-1,1-Dimethyl-1-(2-buten-1-yl)silanol ((E)-1) Si Cl acetate buffer ph = 5 ether, rt (E)-12 (E)-1 Si OH To a single-necked, 1-L, round-bottom flask equipped with a magnetic stir bar was added 250 ml of 1 M acetate buffer (ph = 5) and ether (20 ml). (E)-2-butenyldimethylchlorosilane (5. g, 9. mmol) was then dissolved in ether ( ml) then added by pipette to the vigorously stirring, heterogeneous mixture of acetate buffer and ether. After being stirred for 5 min, the reaction mixture was then poured into a 1-L separatory funnel and diluted with ether (50 ml). The aqueous phase was separated and washed with ether (2 x 50 ml), The three separate organic extracts were then sequentially washed with sat. aq. NaHCO (50 ml) and the ph of the resulting aqueous wash was checked with litmus paper to ensure alkalinity. The organic extracts were then washed with brine (50 ml), combined, dried over Na 2 SO, and then filtered through a pad of silica gel (10 g). The filtrate was concentrated (ambient temp., 20 mm Hg) and the residue purified by column chromatography (SiO 2, 0 mm x 20 cm, pentane/et 2 O, :1). Fractions were combined, concentrated to ~20 ml (ambient temp., 20 mm Hg) and then was transferred to a dry box for conversion to its sodium salt. Data for ((E)-1): TLC: R f 0.2 (pentane/et 2 O, :1) [silica gel, aqueous KMnO ]

11 S11 Preparation of Sodium (E)-1,1-Dimethyl-1-(2-buten-1-yl)silanolate (Na + (E)-1 - ) Si OH NaH THF, rt 2 1' 1' Si O - Na + 1 (E)-1 (E)-Na In a dry box, washed NaH (1.0 g,.2 mmol, 1.1 equiv) and THF (10 ml) were combined in a 50-mL, single-neck, round-bottomed flask containing a magnetic stir bar. In a separate 50-mL, single-neck, round-bottomed flask containing (E)-2-butenyldimethylsilanol (9. mmol) was added THF (10 ml), this solution was then mixed and added drop-wise over 10 min to the stirred suspension of NaH. After being stirred for 0 min, the resulting mixture was filtered through a glass-fritted filter (M,.5 cm x.5 cm) into a 100-mL Schlenk flask. The filtrate was concentrated (ambient temp., 20 mm Hg) to afford a colorless amorphous solid. Hexane (10 ml) was then added and the resulting solution was concentrated (ambient temp., 0.5 mm Hg) to afford 5.00 g (%) of Na + (E)-1 - as a white powder. Data for (Na + (E)-1 - ): 1 H NMR: (500 MHz, C 6 D 6 ) 5.0 (m, 1 H, HC(2)), 5.2 (m, 1 H, HC()), 1.2 (dd, J = 6., 1.2, H, HC()), 1.52 (d, J =.9, 2 H, HC(1)), 0.1 (s, 6 H, HC(1 )). 1 C NMR: (126 MHz, C 6 D 6 ) 11.6 C(2), 121. C(), 2.5 C(1), 1. C(),.2 (C(1 ).

12 S12 Preparation of (Z)-1,1-Dimethyl-1-(2-buten-1-yl)silanol ((Z)-1) Si Cl acetate buffer ph = 5 ether, rt Si OH (Z)-12 (Z)-1 To a single-necked, 1-L, round-bottom flask equipped with a magnetic stir bar was added 19 ml of 1 M acetate buffer (ph = 5) and ether (15 ml). (Z)-2-Butenyldimethylchlorosilane (.6 g, 0.0 mmol) was then dissolved in ether (25 ml) then added by pipette to the vigorously stirring, heterogeneous mixture of acetate buffer and ether. After being stirred for 5 min, the reaction mixture was then poured into a 1-L separatory funnel and diluted with ether (50 ml). The aqueous phase was separated and washed with ether (2 x 50 ml), The three separate organic extracts were then sequentially washed with sat. aq. NaHCO (50 ml) and the ph of the resulting aqueous wash was checked with litmus paper to ensure alkalinity. The organic extracts were then washed with brine (50 ml), combined, dried over Na 2 SO, and then filtered through a pad of silica gel (10 g). The filtrate was concentrated (ambient temp., 20 mm Hg) and the residue purified by column chromatography (SiO 2, 0 mm x 20 cm, pentane/et 2 O, :1). Fractions were combined, concentrated to ~20 ml (ambient temp., 20 mm Hg) and then was transferred to a dry box for conversion to its sodium salt. Data for ((Z)-1): TLC: R f 0.2 (pentane/et 2 O, :1) [silica gel, aqueous KMnO ]

13 S1 Preparation of Sodium (Z)-1,1-Dimethyl-1-(2-buten-1-yl)silanolate (Na + (Z)-1 - ) Si OH NaH THF, rt 1' 1' 2 Si O - Na + (Z)-1 (Z)-Na In a dry box, washed NaH (00 mg,.0 mmol, 1.1 equiv) and THF (10 ml) were combined in a 50-mL, single-neck, round-bottomed flask containing a magnetic stir bar. In a separate 50-mL, single-neck, round-bottomed flask containing (Z)-2-butenyldimethylsilanol (0.0 mmol) was added THF (10 ml), this solution was then mixed and added drop-wise over 10 min to the stirred suspension of NaH. After being stirred for 0 min, the resulting mixture was filtered through a glass-fritted filter (M,.5 cm x.5 cm) into a 100-mL Schlenk flask. The filtrate was concentrated (ambient temp., 20 mm Hg) to afford a colorless amorphous solid. Hexane (10 ml) was then added and the resulting solution was concentrated (ambient temp., 0.5 mm Hg) to afford. g (5%) of Na + (Z)-1 - as a colorless solid. Data for (Na + (Z)-1 - ): 1 H NMR: (500 MHz, C 6 D 6 ) 5. (m, 1 H, HC(2)), 5.9 (m, 1 H, HC()), 1.66 (d, J = 6.6, H, HC()), 1.55 (d, J =.6, 2 H, HC(1)), 0.12 (s, 6 H, HC(1 )). 1 C NMR: (126 MHz, C 6 D 6 ) 10.1 C(2), C(), 2. C(1), 12.9 C(),.6 (C(1 ). 1

14 S1 General Procedure I. Preparative Cross-coupling of Sodium 2-Propenyldimethylsilanolate with Aryl Bromides Br Si + O - Na + R 2.5 equiv 1.0 equiv APC (2.5 mol%) DME (0.5 M), 5 o C R To a 5-mL, single-necked, round-bottomed flask containing a magnetic stir bar, equipped with a reflux condenser and an argon inlet capped with a septum was added allylpalladium chloride dimer (APC, 9.2 mg, mmol, equiv). The flask was then sequentially evacuated and filled with argon three times. The aryl bromide (1.0 mmol) was then added by syringe. Sodium 2-propenyldimethylsilanolate (6 mg, 2.5 mmol, 2.5 equiv), pre-weighed into a 10-mL, two-necked, round-bottomed flask in a dry-box, was then dissolved in DME (2.0 ml) then added to the aryl bromide by syringe. The reaction mixture was heated in a preheated oil bath to 5 o C under argon. After complete consumption of the aryl bromide was observed by GC analysis, the mixture was cooled to rt, filtered through silica gel (2 cm x 2 cm) in a glass-fritted filter (coarse, 2 cm x 5 cm) and the filter cake washed with ether ( x 10 ml). The filtrate was concentrated (ambient temp., 20 mm Hg) and the residue was purified by column chromatography (silica gel or C-1 reverse phase) followed by Kugelrohr distillation or recrystallization to afford the product. General Procedure II. Preparative Cross-Coupling of Sodium 2-Butenyldimethylsilanolate with Aryl Bromides Br Si + O - Na + R 2.0 equiv 1.0 equiv Pd(dba) 2 (5 mol%) nbd (5 mol %) toluene (0.5 M), 0 o C R

15 S15 To an oven dried, 5-mL, single-neck, round-bottomed flask, containing a magnetic stir bar, equipped with a reflux condenser and an argon inlet capped with a septum was added Pd(dba) 2 (2. mg, 0.05 mmol, 0.05 equiv). The flask was then sequentially evacuated and filled with argon three times. The aryl bromide (1.0 mmol) was then added by syringe. Sodium 2- butenyldimethylsilanolate (0 mg, 2.0 mmol, 2.0 equiv), pre-weighed into a 10-mL, twonecked, round-bottomed flask in a dry-box, was then dissolved in toluene (2.0 ml) and then norbornadiene (nbd, 5.2 µl, 0.05 mmol, equiv) was added by syringe. The solution of Na and nbd in toluene was then added to the aryl bromide by syringe. The reaction mixture was heated under argon to 0 o C in a preheated oil bath. After complete consumption of the aryl bromide was observed by GC analysis, the mixture was cooled to rt, filtered through silica gel (2 cm x 2 cm) in a glass-fritted filter (C, 2 cm x 5 cm) and the filter cake washed with ether ( x 10 ml). The filtrate was concentrated (ambient temp., 20 mm Hg) and the residue was purified by column chromatography (silica gel or C-1 reverse phase) followed by Kugelrohr distillation or recrystallization to afford the product. General Procedure III. Small-scale Cross-coupling of Sodium 2- Propenyldimethylsilanolate with -Bromoanisole (Dry-Box Set-Up) Br Si + O - Na + O 1. equiv 1.0 equiv APC (2.5 mol%) toluene (0.5 M), 0 o C O In a 5-mL, single-necked, round-bottomed flask containing a magnetic stir bar, equipped with a reflux condenser was combined APC (.0 mg, mmol, equiv), biphenyl (0 mg, 0.26 mmol), -bromoanisole (5.0 mg, 0.0 mmol), toluene (0.0 ml) and Sodium 2- propenyldimethylsilanolate (2 mg, 0.52 mmol, 1. equiv). The flask was then sealed with a

16 S16 septum, removed from the dry-box, and heated in a preheated oil bath to 0 o C under argon using a stainless steel 16 gauge needle. Aliquots (50 µl) were removed from the reaction mixture by syringe, then were quenched with 10% 2-(dimethylamino)ethanethiol hydrochloride solution (0.25 ml), and were extracted with EtOAc (1 ml). The organic extract was then filtered through a small plug of silica gel in a pipette (0.5 cm x 1.0 cm) and the filter cake washed with EtOAc (0.5 ml). The sample was then analyzed by GC or GC/MS using thods 1, 2, or. General Procedure IV. Small-scale Cross-coupling of Sodium 2- Propenyldimethylsilanolate or Sodium 2-Butenyldimethylsilanolate with Aryl Bromides (Bench-Top Set-Up) Si O - Na + + R Br [Pd] (loading) ligand (loading) solvent, temp R In a 5-mL, single-necked, round-bottomed flask containing a magnetic stir bar, equipped with a reflux condenser was combined palladium catalyst, ligand, and biphenyl (internal standard). The flask was then sequentially evacuated and filled with argon three times. The aryl bromide (1.0 equiv) was then added by syringe. The silanolate pre-weighed into a 10-mL, twonecked, round-bottomed flask in a dry-box, was then dissolved in solvent, and added to the aryl bromide by syringe. The reaction mixture was heated under argon in a preheated oil bath. Aliquots (50 µl) were removed from the reaction mixture by syringe, quenched with 10% 2- (dimethylamino)ethanethiol hydrochloride solution (0.25 ml), and were extracted with EtOAc (1 ml). The organic extract was then filtered through a small plug of silica gel (0.5 cm x 1.0 cm) and the filter cake washed with EtOAc (0.5 ml). The sample was then analyzed by GC or GC/MS using thods 1, 2, or.

17 S1 1-thoxy--(2-propen-1-yl)benzene (a) 5 6 O 1 2 Following General Procedure I, APC (9.2 mg, mmol, equiv), -bromoanisole (1 mg, 1.0 mmol), Na (6 mg, 2.5 mmol, 2.5 equiv), and DME (2.0 ml) were combined and heated to 5 o C. After h, the mixture was cooled to rt, filtered through silica gel (2 cm x 2 cm) and the filter cake washed with ether. Purification by silica gel chromatography (20 cm X 20 mm, hexane/etoac, gradient 100:0 to 20:1) followed by Kugelrohr distillation afforded 119 mg (0%) of a as a clear, colorless oil. Spectroscopic data matched those reported in the literature. 1 Data for (a): bp: 90 C (10 mmhg, ABT) 1 H NMR: (500 MHz, CDCl ).1 (d, J =.5, 2 H, HC()), 6. (d, J =.5, 2 H, HC(2)), 5.99 (ddt, J = 16., 10., 6.6, 1 H, HC(6)), 5.09 (m, 2 H, HC()),.1 (s, H, HC()),.6 (d, J = 6.6, 2 H, HC(5)). 1 C NMR: (126 MHz, CDCl ) 15.2 C(1), 1.2 C(6), 12. C(), 129. C(), 115. C(), 11.1 C(2), 55.5 C(), 9.6 C(5). IR: (film) 0 (m), 02 (m), 00 (m), 29 (m), 295 (m), 29 (m), 2906 (m), 25 (m), 169 (m), 1611 (s), 15 (m), 1511 (s), 16 (s), 11 (m), 121 (w), 101 (s), 12 (s), 11 (s), 1111 (m), 10 (s), 1012 (w), 995 (m), 91 (s), 2 (m),

18 S1 0 (m), 15 (m), 61 (m), 0 (w), 69 (m), 62 (m). MS: (EI, 0eV) 1 (M +, 100), 1 (19), 121 (0), 105 (1), 91 (15), (16). TLC: R f 0.5 (hexanes/etoac, 20:1) [silica gel, UV] GC: t R : 6.21 min (GC thod 1). 1-thoxy-2-(2-propen-1-yl)benzene (b) O 2 10 Following General Procedure I, APC (9.2 mg, mmol, equiv), 2-bromoanisole (1 mg, 1.0 mmol), Na (6 mg, 2.5 mmol, 2.5 equiv), and DME (2.0 ml) were combined and heated to 5 o C. After 12 h, the mixture was cooled to rt, filtered through silica gel (2 cm x 2 cm) and the filter cake washed with ether. Purification by silica gel chromatography (20 cm X 20 mm, hexane/etoac, gradient 100:0 to 50:1) followed by Kugelrohr distillation afforded 116 mg (%) of b as a clear, colorless oil. Spectroscopic data matched those reported in the literature. 19 Data for (b): bp: 5 C (11 mmhg, ABT) 1 H NMR: (500 MHz, CDCl ).21 (td, J =.2 and 1., 1 H, HC()),.15 (dd, J =. and 1., 1 H, HC(5)), 6.92 (td, J =. and 1.0, 1 H, HC()), 6. (d, J =.2, 1 H, HC(2)), 6.01 (ddt, J = 16., 10., 6.6, 1 H, HC()), 5.06 (m, 2 H, HC(9)),. (s, H, HC(10)),.0 (d, J = 6.6, 2 H, HC()).

19 S19 1 C NMR: (126 MHz, CDCl ) 15.5 C(1), 1. C(), 10.0 C(5), 12. C(6), 12.6 C(2), 120. C(), C(), C(9), 55.6 C(10),.5 C(). IR: (film) 0 (m), 00 (m), 29 (m), 26 (m), 16 (m), 1600 (m), 19 (s), 16 (s), 19 (m), 1290 (m), 125 (s), 11 (m), 1126 (m), 1050 (m), 102 (s), 996 (m), 52 (s). MS: (EI, 0eV) 1 (M +, 100), 1 (25), 119 (22), 115 (0), 105 (), 91 (5), (1), 65 (10), 55 (). TLC: R f 0.2 (hexanes/etoac, 50:1) [silica gel, UV] GC: t R :.626 min (GC thod 2). N,N-Dimethyl--(2-propen-1-yl)benzenamine (c) 1 5 N 2 6 Following General Procedure I, APC (9.2 mg, mmol, equiv), -bromo-n,ndimethylaniline (200 mg, 1.0 mmol), Na (6 mg, 2.5 mmol, 2.5 equiv), and DME (2.0 ml) were combined and heated to 5 o C. After h, the mixture was cooled to rt, filtered through silica gel (2 cm x 2 cm) and the filter cake washed with ether. Purification by silica gel chromatography (20 cm X 20 mm, pentane/ether, gradient 100:0 to 50:1) followed by Kugelrohr distillation afforded 15 mg (%) of c as a clear, colorless oil. Spectroscopic data matched those reported in the literature. 20

20 S20 Data for (c): bp: 105 C (5 mmhg, ABT) 1 H NMR: (500 MHz, CDCl ).0 (d, J =.6, 2 H, HC(2)), 6. (d, J =.6, 2 H, HC()), 5.9 (ddt, J = 16., 10.0, 6. 1 H, HC(6)), 5.05 (m, 2 H, HC()),.2 (d, J = 6., 2 H, HC(5)), 2.9 (s, 6 H, HC()). 1 C NMR: (126 MHz, CDCl ) 19.5 C(), 1.6 C(6), 129. C(1), 12.5 C(2), 115. C(), 11. C(), 1.2 C(), 9.5 C(5). IR: (film) 06 (m), 00 (m), 296 (m), 292 (m), 25 (m), 299 (m), 16 (m), 1615 (s), 156 (w), 1521 (s), 19 (m), 1 (m), 112 (w), 16 (s), 12 (w), 122 (m), 1190 (w), 116 (m), 112 (m), 1060 (w), 99 (m), 9 (m), 911 (m), 25 (m), 02 (s). MS: (EI, 0eV) 161 (M +, 100), 1 (6), 11 (1), 91 (12), TLC: R f 0.25 (pentane/ether, 50:1) [silica gel, UV] GC: t R : 5. min (GC thod 2).

21 S21 N,N-Dimethyl-2-(2-propenyl)benzenamine (d) N 2 10 Following General Procedure I, APC (9.2 mg, mmol, equiv), 2-bromo-N,Ndimethylaniline (200 mg, 1.0 mmol), Na (6 mg, 2.5 mmol, 2.5 equiv), DME (2.0 ml) were combined and heated to 5 o C. After 12 h, the mixture was cooled to rt, filtered through silica gel (2 cm x 2 cm) and the filter cake washed with ether. Purification by silica gel chromatography (20 cm X 20 mm, hexane/etoac, gradient 100:0 to 50:1) followed by Kugelrohr distillation afforded 15 mg (%) of d as a clear, colorless oil. Spectroscopic data matched those reported in the literature. 21 Data for (d): bp: 5 C (9 mmhg, ABT) 1 H NMR: (500 MHz, CDCl ).20 (d, J =., 1 H, HC()),.19 (t, J =.6, 1 H, HC(5)),.10 (d, J =., 1 H, HC()),.02 (t, J =., 1 H, HC()), 6.01 (ddt, J = 16., 10., 6.6, 1 H, HC()), 5.11 (m, 2 H, HC(9)),.50 (d, J = 6.6, 2 H, HC()), 2.69 (s, 6 H, HC(10). 1 C NMR: (126 MHz, CDCl ) 152. C(1), 1.1 C(), 1. C(2), 10. C(5), 12.1 C(), 12. C(), 119. C(6), C(9), 5.2 C(10), 5.2 C(). IR: (film) 05 (m), 021 (m), 29 (m), 299 (s), 2 (m), 260 (m), 226 (s), 2 (s), 2610 (w), 226 (w), 190 (w), 126 (w), 16 (m), 159 (m), 19 (s), 151 (s),

22 S (m), 11 (m), 1156 (s), 1096 (m), 109 (m), 995 (m), 950 (s), 912 (s), 66 (s). MS: (EI, 0eV) 161 (M +, 100), 16 (52), 12 (), 11 (0), 10 (), 91 (25), (1), 65 (10). TLC: R f 0.12 (hexanes/etoac, 50:1) [silica gel, UV] GC: t R :.91 min (GC thod 2). 1-(1,1-Dimethylethyl)-(2-propen-1-yl)benzene (e) Following General Procedure I, APC (9.2 mg, mmol, equiv), -bromo-tertbutylbenzene (21 mg, 1.0 mmol), Na (6 mg, 2.5 mmol, 2.5 equiv), and DME (2.0 ml) were combined and heated to 5 o C. After 9 h, the mixture was cooled to rt, filtered through silica gel (2 cm x 2 cm) and the filter cake washed with ether. Purification by silica gel chromatography (20 cm X 20 mm, pentane) and C-1 reverse phase chromatography (20 cm x 10 mm, CN/H 2 O, 9:1) followed by Kugelrohr distillation afforded 12 mg (%) of e as a clear, colorless oil. Spectroscopic data matched those reported in the literature. 22 Data for (e): bp: 5 C (5 mmhg, ABT) 1 H NMR: (500 MHz, CDCl ). (d, J =., 2 H, HC()),.1 (d, J =., 2 H, HC(2)), 5.99 (ddt, J = 16.9, 10.0, 6. 1 H, HC(6)), 5.09 (m, 2 H, HC()),. (d, J = 6., 2 H, HC(5)), 1.2 (s, 9 H, HC(9)).

23 S2 1 C NMR: (126 MHz, CDCl ) 19.1 C(), 1.9 C(6), 1. C(1), 12. C(), C(2), C(), 0.0 C(5),.6 C(), 1. C(9). IR: (film) 09 (w), 05 (w), 025 (w), 00 (w), 296 (m), 2905 (m), 269 (m), 16 (w), 1515 (m), 199 (w), 15 (w), 160 (w), 12 (w), 11 (w), 19 (w), 16 (w), 1269 (w), 120 (w), 1110 (w), 1020 (w), 99 (w), 91 (w), (w), (w), 06 (w). MS: (EI, 0eV) 1 (2), 15 (M +, 100), 11 (12), 11 (1), 105 (10), 91 (1), 5 (1). TLC: R f 0.5 (pentane) [silica gel, UV] GC: t R : 5.26 min (GC thod 2). 1-[[(Triethylsilyl)oxy]methyl]--(2-propenyl)benzene (f) O Si Following General Procedure I, APC (9.2 mg, mmol, equiv), - bromotriethylsilylbenzyl ether (01 mg, 1.0 mmol), Na (6 mg, 2.5 mmol, 2.5 equiv), and DME (2.0 ml) were combined and heated to 5 o C. After h, the mixture was cooled to rt, filtered through silica gel (2 cm x 2 cm) and the filter cake washed with ether. Purification by silica gel chromatography (20 cm X 20 mm, hexane/etoac, gradient 100:0 to 20:1) followed by Kugelrohr distillation afforded 225 mg (6%) of f as a clear, colorless oil.

24 S2 Data for (f): bp: 10 C (2 mmhg, ABT) 1 H NMR: (500 MHz, CDCl ).26 (t, J =.6, 1 H, HC(5)),.1 (d, J =.9, 2 H, HC(), HC(6)),.0 (d, J =.6, 1 H, HC(2)), 5.9 (ddt, J = 16.9, 10.1, 6. 1 H, HC()), 5.0 (m, 2 H, HC(9)),.2 (s, 2 H, HC(10)),.9 (d, J = 6., 2 H, HC()), 0.9 (t, J =.9, 9 H, HC(12)), 0.65 (q, J =.9, 6 H, HC(11)). 1 C NMR: (126 MHz, CDCl ) 11. C(1), 10.2 C(), 1. C(), 12.5 C(), 12.5 C(6), 126. C(5), 12. C(2), C(9), 65.0 C(10), 0.5 C(),.0 C(12),. C(11). IR: (film) 059 (m), 005 (m), 295 (s), 2911 (s), 26 (s), 22 (w), 169 (m), 1609 (m), 1591 (w), 1 (m), 15 (m), 11 (m), 12 (m), 129 (s), 115 (s), 1105 (s), 10 (s), 1006 (s), 9 (m), 91 (s), 20 (s), (s), 00 (s), 669 (m). MS: (EI, 0eV) 2 (M + - CH 2 CH, 100), 20 (1), 15 (16), 11 (), 115 (11), 91 (1). HRMS: (CI) calc for C 16 H 2 OSi (M + +H): 26.11; found: TLC: R f 0.1 (hexanes/etoac, 20:1) [silica gel, UV] GC: t R :.10 min (GC thod ).

25 S25 2-(2-Propen-1-yl)naphthalene (g) Following General Procedure I, APC (9.2 mg, mmol, equiv), 2- bromonaphthalene (20 mg, 1.0 mmol), Na (6 mg, 2.5 mmol, 2.5 equiv), and DME (2.0 ml) were combined and heated to 5 o C. After 9 h, the mixture was cooled to rt, filtered through silica gel (2 cm x 2 cm) and the filter cake washed with ether. Purification by silica gel chromatography (20 cm X 20 mm, pentane) and C-1 reverse phase chromatography (20 cm x 10 mm, OH/H 2 O, 9:1) followed by Kugelrohr distillation afforded 120 mg (1%) of g as a clear, colorless oil. Spectroscopic data matched those reported in the literature. 2 Data for (g): bp: 62 C (0.1 mmhg, ABT) 1 H NMR: (500 MHz, CDCl ).2 (m, H, HC(), HC(6), HC(9)),.65 (bs, 1 H, HC(1)),.6 (pd, J = 6.9, H, HC(), HC()),.6 (dd, J =., 1. 1 H, HC()), 6.0 (ddt, J = 16., 10.1, 6., 1 H, HC(12)), 5.16 (m, 2 H, HC(1)),.5 (d, J = 6., 2 H, HC(11)). 1 C NMR: (126 MHz, CDCl ) 1. C(2), 1.6 C(12), 1.9 C(10), 12. C(5), 12.2 C(), 12.9 C(9), 12. C(6), 12. C(1), C(), C(), C(), 116. C(1), 0.6 C(11). IR: (film) 05 (w), 29 (w), 2900 (w), 2 (w), 1919 (w), 11 (w), 16 (w), 1600 (w), 1560 (w), 152 (w), 150 (w), 11 (w), 112 (w), 16 (w), 126 (w), 112 (w), 112 (w), 101 (w), 99 (w), 960 (w), 91 (w), 51 (w), 1 (w), 1 (w), 52

26 S26 (w). MS: (EI, 0eV) 16 (M +, 100), 15 (26), 11 (1), 115 (1). TLC: R f 0.25 (pentane) [silica gel, UV] GC: t R : 6.1 min (GC thod 2). 1-(2-Propen-1-yl)naphthalene (h) Following General Procedure I, APC (9.2 mg, mmol, equiv), 1- bromonaphthalene (20 mg, 1.0 mmol), Na (6 mg, 2.5 mmol, 2.5 equiv), and DME (2.0 ml) were combined and heated to 5 o C. After 2 h, the mixture was cooled to rt, filtered through silica gel (2 cm x 2 cm) and the filter cake washed with ether. Purification by silica gel chromatography (20 cm x 20 mm, hexane) and C-1 reverse phase chromatography (20 cm x 10 mm, OH/H 2 O, 9:1) followed by Kugelrohr distillation afforded 1 mg (5%) of h as a clear, colorless oil. Spectroscopic data matched those reported in the literature. 2 Data for (h): bp: 5 C (1.0 mmhg, ABT) 1 H NMR: (500 MHz, CDCl ).05 (d, J =.1, 1 H, HC(9)),. (d, J =.6, 1 H, HC(6)),.6 (d, J =.1, 1 H, HC()),.51 (m, 2 H, HC(), HC()),. (m, 1 H, HC()),.6 (d, J = 6.6, 1 H, C(2)), 6.1 (ddt, J = 16., 10.5, 6., 1 H, HC(12)), 5.12 (m, 2 H, HC(1)),.6 (d,

27 S2 J = 6., 2 H, HC(11)). 1 C NMR: (126 MHz, CDCl ) 1.2 C(12), 16. C(1), 1.1 C(5), 12.2 C(10), 12.9 C(6), 12.2 C(), C(), C(), C(), 125. C(9), 12. C(2), 116. C(1),.5 C(11). IR: (film) 06 (m), 005 (m), 29 (m), 2912 (m), 29 (w), 192 (w), 11 (w), 102 (w), 165 (w), 16 (m), 159 (m), 1510 (m), 10 (w), 196 (m), 152 (w), 1296 (w), 1259 (w), 12 (w), 121 (w), 1165 (w), 112 (w), 106 (w), 1016 (m), 99 (m), 96 (w), 91 (m), 5 (w), 91 (m), 6 (m), 2 (w). MS: (EI, 0eV) 16 (M + 100), 15 (65), 11 (22), 115 (2). TLC: R f 0.29 (hexanes) [silica gel, UV] GC: t R : 9.96 min (99.%) (GC thod 1). 2-thoxy-6-(2-propenyl)naphthalene (i) 2 1 O Following General Procedure I, APC (9.2 mg, mmol, equiv), 2-bromo-6- methoxynaphthalene (2 mg, 1.0 mmol), Na (6 mg, 2.5 mmol, 2.5 equiv), and DME (2.0 ml) were combined and heated to 5 o C. After 6 h, the mixture was cooled to rt, filtered through silica gel (2 cm x 2 cm) and the filter cake washed with ether. Purification by silica gel chromatography (20 cm X 20 mm, pentane/ether/ch 2 Cl 2, gradient 99:0:1 to 9:2:1) followed by recrystallization from pentane afforded 1 mg (95%) of i as white needles. Spectroscopic data

28 S2 matched those reported in the literature. 25 Data for (i): mp: 5-55 o C 1 H NMR: (500 MHz, CDCl ).69 (d, J =., 2 H, HC(), HC()),.5 (d, J = 0., 1 H, HC(5)),.1 (dd, J =. and 1., 1 H, HC()), 6. (d, J =.2, 1 H, HC(2), HC(10)), 6.06 (ddt, J = 1.1, 10.2, 6.6, 1 H, HC(12)), 5.1 (m, 2 H, HC(1)),.92 (s, H, HC(1)),.5 (d, J = 6.6, 2 H, HC(11)). 1 C NMR: (126 MHz, CDCl ) 15.5 C(1), 1. C(12), 15. C(6), 1. C(9), 129. C(), C(), 12.1 C(5), 12.1 C(), 126. C(), C(2), C(1), C(10), 55.5 C(1), 0. C(11). IR: (film) 051 (w), 01 (w), 2962 (w), 29 (w), 290 (w), 26 (w), 25 (w), 166 (w), 1629 (w), 160 (m), 1505 (w), 1 (m), 161 (w), 12 (w), 1 (w), 126 (m), 126 (m), 120 (m), 1160 (m), 1120 (w), 100 (m), 1000 (w), 919 (m), 5 (m), 25 (m). MS: (EI, 0eV) 19 (M +, 100), 1 (1), 16 (1), 155 (21), 19 (6), 12 (1), 115 (), 99 (), (2), 6 (), 6 (5). TLC: R f 0.9 (pentane/et 2 O/CH 2 Cl 2, 9/2:1) [silica gel, UV] GC: t R :.196 min (GC thod 2).

29 S29 1,,5-Trimethyl-2-(2-propenyl)benzene (j) Following General Procedure I, APC (9.2 mg, mmol, equiv), Ph PO (1 mg, 0.05 mmol, equiv), 2-bromomesitylene (199 mg, 1.0 mmol), Na (691 mg, 5.0 mmol, 5.0 equiv), and dioxane (2.0 ml) were combined and heated to 100 o C. After h, the mixture was cooled to rt, filtered through silica gel (2 cm x 2 cm) and the filter cake washed with ether. Purification by silica gel chromatography (20 cm X 20 mm, hexane) and C-1 reverse phase chromatography (20 cm x 10 mm, CN/H 2 O, 9:1) followed by Kugelrohr distillation afforded 12 mg (0%) of j as a clear, colorless oil. Spectroscopic data matched those reported in the literature. 26 Data for (j): bp: 100 C (10 mmhg, ABT) 1 H NMR: (500 MHz, CDCl ) 6.6 (s, 2 H, HC()), 5.9 (ddt, J = 1.1, 10.1, 5. 1 H, HC(6)),.99 (dq, J = 10.1, 1., 1 H, H cis C()),. (dq, J = 1.1, 1., 1 H, H trans C()),. (dt, J = 5., 1., 2 H, HC(5)), 2.2 (s, 9 H, HC(), HC(9)). 1 C NMR: (126 MHz, CDCl ) 16. C(6), 15. C(1), 15.6 C(), 1. C(2), C(), 11.9 C(),.6 C(5), 21.1 C(), 20.0 C(9). IR: (film) 0 (w), 002 (m), 29 (m), 296 (m), 2919 (m), 261 (m), 21 (w), 16 (m), 161 (w), 15 (w), 1559 (w), 1 (m), 1 (m), 15 (w), 125 (w),

30 S (w), 101 (w), 991 (w), 910 (m), 50 (m), 96 (w), 1 (w). MS: (EI, 0eV) 160 (M +, ), 15 (100), 1 (16), 115 (12), 105 (11), 91 (10). TLC: R f 0.5 (pentane) [silica gel, UV] GC: t R : 5.1 min (99.%) (GC thod ). Phenyl[-(1E)1-propen-1-ylphenyl]methanone, (9) O Following General Procedure I, APC (9.2 mg, mmol, equiv), - bromobenzophenone (01 mg, 1.0 mmol), Na (6 mg, 2.5 mmol, 2.5 equiv), and DME (2.0 ml) were combined and heated to 5 o C. After 1 h, the mixture was cooled to rt, filtered through silica gel (2 cm x 2 cm) and the filter cake washed with ether. Purification by silica gel chromatography (0 cm X 0 mm, hexane/etoac, gradient 100:0 to 20:1) afforded 169 mg (6%) of 9 as a pale-yellow solid. Spectroscopic data matched those reported in the literature. 2 Data for (9): mp: 62-6 o C 1 H NMR: (00 MHz, CDCl ). (m, H, HC(), HC()),.5 (m, 1 H, HC(9)),. (m, 2 H, HC()),.2 (m, 2 H, HC(2)), 6.2 (m, 2 H, HC(10), HC(11)), 1.9 (d, J = 5.1, H, HC(12)).

31 S1 1 C NMR: (126 MHz, CDCl ) C(5), 12.1 C(1), 1.9 C(6), 15.6 C(), 12.2 C(9), 10.6 C(), 10. C(11), C(), C(10), 12.2 C(), C(2), 1. C(12). IR: (film) 01 (m), 1651 (s), 1602 (s), 159 (w), 1 (m), 111 (m), 11 (m), 12 (s), 1222 (m), 120 (w), 11 (m), 1150 (w), 96 (m), 95 (w), 99 (m), 92 (m), 61 (w). MS: (EI, 0eV) 222 (M +, ), 15 (100), 115 (2), 105 (20), (19). TLC: R f 0. (hexanes/etoac, 20:1) [silica gel, UV] GC: t R :.99 min (GC thod 2). 1-thoxy--(1-methyl-2-propen-1-yl)benzene (1a) 9 O Following General Procedure II, Pd(dba) 2 (2. mg, 0.05 mmol, equiv), - bromoanisole (1 mg, 1.0 mmol), Na (0 mg, 2.0 mmol, 2.0 equiv), nbd (5.2 µl, 0.05 mmol, equiv), and toluene (2.0 ml) were combined and heated to 5 o C. After 6 h, the mixture was cooled to rt, filtered through silica gel (2 cm x 2 cm) and the filter cake washed with ether ( x 10 ml). Purification by silica gel chromatography (20 cm x 20 mm, hexane/etoac, gradient 100:0 to 20:1) followed by Kugelrohr distillation afforded 5 mg (6%) of 1a as a clear, colorless oil. Spectroscopic data matched those reported in the literature. 2

32 S2 Data for (1a): bp: 120 C (10 mmhg, ABT) 1 H NMR: (500 MHz, CDCl ).1 (m, 2 H, HC()), 5.99 (m, 2 H, HC(2)), 5.99 (ddd, J = 16.9, 10., 6., 1 H, HC()), 5.0 (m, 2 H, HC()),.0 (s, H, HC(9)),. (ap, J =.0, 1 H, HC(6)), 1.5 (d, J =.0, H, HC(5)). 1 C NMR: (126 MHz, CDCl ) 15.2 C(), 1.9 C(), 1.9 C(1), 12. C(2), 11.0 C(), 11.0 C(), 55.5 C(9), 2.6 C(6), 21.1 C(5). IR: (film) 2962 (m), 2 (m), 165 (w), 166 (m), 1610 (m), 15 (m), 1512 (m), 15 (m), 120 (w), 169 (w), 125 (m), 11 (m), 1109 (w), 10 (m), 912 (m), 0 (m), 9 (w). MS: (EI, 0eV) 162 (M +, 62), 1 (100), 11 (12), 115 (11), 91 (2). TLC: R f 0. (hexane/etoac, 20:1) [silica gel, UV] GC: γ-t R : 5.15 min, α-t R : 5.5 and 5.5 min (29:1 [2.:1], γ:α [E or Z]) (GC thod ). N,N-Dimethyl--(1-thyl-2-propen-1-yl)benzenamine (1c) 9 N Following General Procedure II, Pd(dba) 2 (2. mg, 0.05 mmol, equiv), -bromo- N,N-dimethylaniline (200 mg, 1.0 mmol), Na (0 mg, 2.0 mmol, 2.0 equiv), nbd (5.2 µl,

33 S 0.05 mmol, equiv), and toluene (2.0 ml) were combined and heated to 5 o C. After 20 h, the mixture was cooled to rt, filtered through silica gel (2 cm x 2 cm) and the filter cake washed with ether ( x 10 ml). Purification by silica gel chromatography (20 cm x 20 mm, pentane/ether, gradient 100:0 to 20:1) followed by Kugelrohr distillation afforded 5 mg (%) of 1c as a clear, colorless oil. Data for (1c): bp: 110 C (10 mmhg, ABT) 1 H NMR: (500 MHz, CDCl ).11 (m, 2 H, HC()), 6. (m, 2 H, HC(2)), 6.00 (ddd, J = 1.0, 10., 6.5, 1 H, HC()), 5.02 (m, 2 H, HC()),.0 (ap, J =.0, 1 H, HC(6)), 2.9 (s, 6 H, HC(9)), 1.5 (d, J =.0, H, HC(5)). 1 C NMR: (126 MHz, CDCl ) 1.2 C(), 12.0 C(1), C(2), 11. C(), C(), 2. C(9), 1.2 C(6), 21.0 C(5). IR: (film) 296 (m), 2 (w), 29 (w), 161 (m), 1521 (s), 1 (w), 1 (w), 1 (m), 122 (w), 1165 (w), 1060 (w), 9 (w), 910 (w), 1 (m). MS: (EI, 0eV) 15 (M +, 100), 160 (9), 1 (20), 115 (12). HRMS: (EI, 0eV) calc for C 12 H 1 N (M + ): ; found: TLC: R f 0.0 (pentane/ether, 20:1) [silica gel, UV] GC: γ-t R : 6.00 min, α-t R : 6.0, 6.52 min (.5:1 [1.:1], γ:α [E or Z]) (GC thod ).

34 S 1-[[(Triethylsilyl)oxy]methyl]--(1-methyl-2-propen-1-yl)benzene (1f) O Si 12 1 Following General Procedure II, Pd(dba) 2 (2. mg, 0.05 mmol, equiv), triethylsilyl -bromobenzyl ether (01 mg, 1.0 mmol), Na (0 mg, 2.0 mmol, 2.0 equiv), nbd (5.2 µl, 0.05 mmol, equiv), and toluene (2.0 ml) were combined and heated to 0 o C. After h, the mixture was cooled to rt, filtered through silica gel (2 cm x 2 cm) and the filter cake washed with ether ( x 10 ml). Purification by silica gel chromatography (20 cm x 20 mm, hexane/etoac, gradient 100:0 to 20:1) followed by Kugelrohr distillation afforded 21 mg (9%) of 1f as a clear, colorless oil. Data for (1f): bp: 15 C (1.0 mmhg, ABT) 1 H NMR: (500 MHz, CDCl ).2 (t, J =.6, 1 H, HC(5)),.1 (m, 2 H, HC() and HC(6)),.10 (d, J =.6, 1 H, HC(2)), 6.00 (ddd, J = 1.1, 10., 6., 1 H, HC(9)), 5.0 (m, 2 H, HC(10)),.2 (s, 2 H, HC(11)),. (ap, J = 6., 1 H, HC()), 1.6 (d, J = 6., H, HC()), 0.9 (t, J =.9, 9 H, HC(1)), 0.65 (q, J =.9, 6 H, HC(12)). 1 C NMR: (126 MHz, CDCl ) 15.5 C(1), 1.2 C(9), 11. C(), 12. C(), C(6), 12.1 C(5), 12. C(2), 11.0 C(10), 6. C(11),.2 C(), 20. C(), 6. C(1),.5 C(12).

35 S5 IR: (film) 2956 (m), 25 (m), 166 (w), 160 (w), 1 (w), 15 (w), 15 (w), 11 (m), 12 (w), 129 (w), 1160 (w), 102 (m), 1016 (m), 911 (w), 19 (w), 1 (m), 0 (w). MS: (EI, 0eV) 25 (M-1, ), 261 (6), 2 (9), 21 (11), 205 (22), 191 (12), 165 (1), 15 (6), 11 (2), 11 (), 10 (100), 91 (22), 5 (2). TLC: R f 0.1 (hexane/etoac, 20:1) [silica gel, UV] GC: γ-t R :.25 min, α-t R :. and.52 min (15:1 [2.:1], γ:α [E or Z]) (GC thod ). 2-(1-thyl-2-propen-1-yl)naphthalene (1g) Following General Procedure II, Pd(dba) 2 (2. mg, 0.05 mmol, equiv), 2- bromonaphthalene (20 mg, 1.0 mmol), Na (0 mg, 2.0 mmol, 2.0 equiv), nbd (5.2 µl, 0.05 mmol, equiv), and toluene (2.0 ml) were combined and heated to 0 o C. After 6 h, the mixture was cooled to rt, filtered through silica gel (2 cm x 2 cm) and the filter cake washed with ether ( x 10 ml). Purification by silica gel chromatography (20 cm x 20 mm, pentane) and C- 1 reverse phase chromatography (20 cm x 10 mm, OH/H 2 O, 9:1) followed by Kugelrohr distillation afforded 15 mg (0%) of 1g as a clear, colorless oil. Spectroscopic data matched those reported in the literature. 29 Data for (1g): bp: 160 C (5 mmhg, ABT)

36 S6 1 H NMR: (500 MHz, CDCl ).0 (m, H, HC(), HC(6), HC(9)),.66 (s, 1 H, HC(1)),.5 (m, 2 H, HC(), HC()),. (m, 1 H, HC()), 6.10 (ddd, J = 16.9, 10., 6.9, 1 H, HC(1)), 5.11 (m, 2 H, HC(1)),.65 (ap, J = 6.9, 1 H, HC(12)), 1. (d, J = 6.9, H, HC(11)). 1 C NMR: (126 MHz, CDCl ) 1. C(1), 1.2 C(2), 1.9 C(10), 12. C(5), 12.2 C(), 12.9 C(9), 12. C(6), C(1), C(), C(), 125. C(), 11. C(1),.5 C(12), 20.9 C(11). IR: (film) 055 (m), 01 (w), 2965 (m), 290 (w), 2 (w), 162 (w), 1600 (w), 150 (w), 152 (w), 112 (w), 1 (w), 125 (m), 1126 (w), 102 (m), 99 (w), 96 (w), 99 (w), 912 (m), 9 (w), 55 (m), 1 (s), (s). MS: (EI, 0eV) 12 (M +, 69), 16 (100), 152 (22), 12 (11). TLC: R f 0.9 (pentane) [silica gel, UV] GC: γ-t R : 6.50 min, α-t R : 6.1 and 6.9 min (25:1 [1.9:1], γ:α [E or Z]) (GC thod ). 1-(1-thyl-2-propen-1-yl)naphthalene (1h) Following General Procedure II, Pd(dba) 2 (2. mg, 0.05 mmol, equiv), 1- bromonaphthalene (20 mg, 1.0 mmol), Na (6 mg, 2.5 mmol, 2.5 equiv), nbd (5.2 µl, 0.05

37 S mmol, equiv), and toluene (2.0 ml) were combined and heated to 0 o C. After 6 h, the mixture was cooled to rt, filtered through silica gel (2 cm x 2 cm) and the filter cake washed with ether ( x 10 ml). Purification by silica gel chromatography (20 cm x 20 mm, pentane) followed by Kugelrohr distillation afforded 116 mg (6%) of 1h as a clear, colorless oil. Spectroscopic data matched those reported in the literature. 0 Data for (1h): bp: 120 C (1 mmhg, ABT) 1 H NMR: (500 MHz, CDCl ).15 (d, J =., 1 H, HC(9)),. (d, J =.9, 1 H, HC(6)),. (d, J =.1, 1 H, HC()),.9 (m, H, HC(2), HC(), HC(), HC()), 6.1 (ddd, J = 1., 10.0, 5. 1 H, HC(1)), 5.15 (m, 2 H, HC(1)),.2 (ap, J =.0, 1 H, HC(12)), 1.5 (d, J =.0, H, HC(11)). 1 C NMR: (126 MHz, CDCl ) 1.1 C(1), 11. C(1), 1.2 C(5), 11. C(10), C(6), 12.0 C(), C(), 125. C(9), C(), 12.9 C(), 12. C(2), 11.9 C(1),.1 C(12), 20.5 C(11). IR: (film) 0 (m), 296 (m), 291 (m), 2 (m), 192 (w), 10 (w), 100 (w), 16 (w), 165 (w), 166 (m), 1596 (m), 1509 (m), 152 (m), 110 (m), 195 (m), 169 (m), 1250 (m), 125 (w), 116 (w), 1016 (m), 99 (m), 912 (m), 59 (w), 9 (m), (m). MS: (EI, 0eV) 12 (M +, 6), 16 (100), 152 (2), 12 (1).

38 S TLC: R f 0.2 (pentane) [silica gel, UV] GC: γ-t R : 6.50 min, α-t R : 6.6 and 6. min (1:1 [1.5:1], γ:α [E or Z]) (GC thod ). 2-thoxy-6-(1-methyl-2-propen-1-yl)naphthalene (1i) O Following General Procedure II, Pd(dba) 2 (2. mg, 0.05 mmol, equiv), 2-bromo- 6-methoxynaphthalene (2 mg, 1.0 mmol), Na (0 mg, 2.0 mmol, 2.0 equiv), nbd (5.2 µl, 0.05 mmol, equiv), and toluene (2.0 ml) were combined and heated to 0 o C. After h, the mixture was cooled to rt, filtered through silica gel (2 cm x 2 cm) and the filter cake washed with ether ( x 10 ml). Purification by silica gel chromatography (20 cm x 20 mm, pentane/ether/ch 2 Cl 2, gradient 99:0:1 to 9:2:1) followed by Kugelrohr distillation afforded 16 mg (69%) of 1i as a clear, colorless oil. Spectroscopic data matched those reported in the literature. 1 Data for (1i): bp: 10 C (5 mmhg, ABT) 1 H NMR: (500 MHz, CDCl ).0 (dd, J =.5, 2., 2 H, HC(), HC()),.5 (s, 1 H, HC(5)),. (dd, J =.5, 1., 1 H, HC()),.1 (m, 2 H, HC(2), HC(10)), 6.09 (ddd, J = 16., 10., 6., 1 H, HC(1)), 5.09 (m, 2 H, HC(1)),.92 (s, H, HC(15)),.61 (ap, J =.0, 1 H, HC(12)), 1.5 (d, J =.0, H, HC(11)).

39 S9 1 C NMR: (126 MHz, CDCl ) 15.5 C(1), 1.6 C(1), 10.9 C(6), 1. C(9), 129. C(), 129. C(), 12.1 C(5), 12.0 C(), 125. C(), 11.9 C(2), 11.5 C(1), C(10), 55.5 C(15),. C(12), 20.9 C(11). IR: (film) 05 (w), 000 (w), 296 (m), 2 (w), 166 (m), 1606 (s), 1506 (m), 1 (m), 16 (w), 1 (w), 115 (w), 191 (m), 169 (w), 1266 (m), 121 (m), 121 (m), 1195 (w), 11 (w), 1162 (m), 10 (m), 92 (w), 912 (w), 9 (w), 51 (m), 10 (m). MS: (EI, 0eV) 26 (M +, 9), 19 (100), 165 (9), 15 (2), 11 (1), 11 (), (22). TLC: R f 0.29 (pentane/ether/ch 2 Cl 2, 9/2:1) [silica gel, UV] GC: γ-t R :. min, α-t R :.6 and. min (2:1 [1.5:1], γ:α [E or Z]) (GC thod ). [-(1-thyl-2-propen-1-yl)phenyl]phenylmethanone (1k) O Following General Procedure II, Pd(dba) 2 (2. mg, 0.05 mmol, equiv), - bromobenzophenone (261 mg, 1.0 mmol), Na (0 mg, 2.0 mmol, 2.0 equiv), nbd (5.2 µl, 0.05 mmol, equiv), and toluene (2.0 ml) were combined and heated to 0 o C. After 20 h, the mixture was cooled to rt, filtered through silica gel (2 cm x 2 cm) and the filter cake washed with ether ( x 10 ml). Purification by silica gel chromatography (20 cm x 20 mm,

40 S0 hexane/etoac, gradient 100:0 to 20:1) followed by Kugelrohr distillation afforded 1 mg (1%) of 1k as a clear, colorless oil. Spectroscopic data matched those reported in the literature. 2 Data for (1k): bp: 10 C (5 mmhg, ABT) 1 H NMR: (500 MHz, CDCl ).9 (m, H, HC(), HC()),.5 (m, 1 H, HC(9)),. (m, 2 H, HC()),. (m, 2 H, HC(2)), 6.02 (m, 1 H, HC(12)), 5.10 (m, 2 H, HC(1)),.56 (ap, J =.0, 1 H, HC(11)), 1.1 (d, J =.0, H, HC(10)). 1 C NMR: (126 MHz, CDCl ) 196. C(5), 150. C(1), 12.5 C(12), 1.1 C(), 15. C(6), 12.5 C(9), 10. C(), 10.2 C(), 12.5 C(), 12.5 C(2), 11.2 C(1),.5 C(11), 20. C(10). IR: (film) 059 (m), 296 (m), 290 (m), 25 (m), 165 (s), 160 (s), 15 (m), 1 (m), 112 (m), 10 (w), 116 (s), 12 (s), 11 (m), 119 (m), 1111 (w), 100 (m), 101 (m), 1000 (m), 9 (m), 92 (m), 50 (m), 95 (m), (m), 00 (m). MS: (EI, 0eV) 26 (M +, 96), 159 (66), 11 (2), 105 (100), (5). TLC: R f 0.2 (hexane/etoac, 20:1) [silica gel, UV] GC: γ-t R :.2 min, α-t R :. and.61 min (1:1 [.:1], γ:α [E or Z]) (GC thod ).

41 S1 1,-Dimethyl-5-(1-methyl-2-propenyl)benzene (1l) Following General Procedure II, Pd(dba) 2 (5.6 mg, 0.10 mmol, equiv), 5-bromoo-xylene (0 mg, 2.0 mmol), Na (61 mg,.0 mmol, 2.0 equiv), nbd (10. µl, 0.10 mmol, equiv), and toluene (.0 ml) were combined and heated to 0 o C. After h, the mixture was cooled to rt, filtered through silica gel (2 cm x 2 cm) and the filter cake washed with ether ( x 10 ml). Purification by silica gel chromatography (20 cm x 0 mm, pentane) followed by Kugelrohr distillation afforded 215 mg (69%) of 1l as a clear, colorless oil. Spectroscopic data matched those reported in the literature. Data for (1l): bp: 10 C (10 mmhg, ABT) 1 H NMR: (500 MHz, CDCl ) 6. (m, H, HC(2), HC()), 6.0 (ddd, J = 1.1, 10., 6.5, 1 H, HC()), 5.0 (m, 2 H, HC()),. (ap, J =.0, 1 H, HC(6)), 2. (s, 6 H, HC(9)), 1. (d, J =.0, H, HC(5)). 1 C NMR: (126 MHz, CDCl ) 15. C(1), 1. C(), 1.1 C(), 12.0 C(), 125. C(2), 11.1 C(),. C(6), 21.6 C(9), 21.0 C(5). IR: (film) 01 (w), 01 (m), 2965 (s), 291 (m), 20 (m), 20 (w), 166 (w), 1602 (m), 15 (m), 110 (m), 10 (w), 105 (w), 125 (m), 116 (w), 106 (m), 99 (m),