Chiral Modification of the Tetrakis(pentafluorophenyl)borate Anion with Myrtanyl Groups

Supporting Information

Chiral Modification of the

Tetrakis(pentafluorophenyl)borate

Anion with Myrtanyl Groups

Phillip Pommerening and Martin Oestreich*

ejoc201901434-sup-0001-SupMat.pdf

Table of Contents

3 Investigation of Substrate-Controlled Hydrogenation of 10 S8 4 Investigation of Catalyst-Controlled Hydrogenation of 10 S9 5 Deuteration Experiments for the Investigation of Triphenylmethane

Formation S10 5.1 (1S,2S,5S)-6,6-Dimethyl-2-(1-(2,3,5,6-tetrafluorophenyl)ethyl-1,2-d2 )bicyclo-[3.1.1]heptane (11-d2) S10 5.2 Lithium tetrakis(4-(1-((1S,2S,5S)-6,6-dimethylbicyclo[3.1.1]heptan-2-yl)ethyl-1,2-d2)-2,3,5,6-tetrafluorophenyl)borate ([Li]+[4-d2]–) S11 5.3 Sodium tetrakis(4-(1-((1S,2S,5S)-6,6-dimethylbicyclo[3.1.1]heptan-2-yl)ethyl-1,2-d2)-2,3,5,6-tetrafluorophenyl)borate ([Na]+[4-d2]–) S12 5.4 Triphenylmethylium tetrakis(4-(1-((1S,2S,5S)-6,6-dimethylbicyclo[3.1.1]-heptan-2-yl)ethyl-1,2-d2)-2,3,5,6-tetrafluorophenyl)borate ([Tr]+[4-d2]–) S13

6 Characterization Data of Mukaiyama Aldol Products S15 6.1 tert-Butyl((1-ethoxyvinyl)oxy)dimethylsilane (18) S15 6.2 Ethyl 3-((tert-butyldimethylsilyl)oxy)-3-phenylpropanoate (20) S15 6.3 tert-Butyl((1-ethoxyvinyl)oxy)dimethylsilan (21) S16 6.4 rac-Ethyl 3-hydroxy-2,2-dimethyl-3-phenylpropanoat (23) S17 6.5 Dimethyl 3,3'-oxybis(2,2-dimethyl-3-(naphthalen-2-yl)propanoate) S18 7 Characterization Data of Diels–Alder Products S19 7.1 endo-Phenyl-(3-phenylbicyclo[2.2.2]oct-5-en-2-yl)methanone (15) S19 7.2 endo-2-Methylbicyclo[2.2.2]oct-5-ene-2-carbaldehyde (17) S19

8 NMR Spectra of All Compounds S20

1

General Informations

All reactions were performed in dried glassware using an MBraun glove box (O2 < 1 ppm,

H2O < 1 ppm) or conventional Schlenk techniques under a static pressure of argon (glove

box) or nitrogen. All reactions under H2 or D2 pressure were carried out in glass vials (50 x 14

mm, Schütt), equipped with a magnetic stir bar and a rubber septum in autoclaves BR-100 or BR-300 (including the appropriate heating blocks, Berghof). The autoclave was purged with N2 (3 x 10 bar) before the vials were placed in the autoclave and the septum was pierced

under a counter flow of N2. The autoclave was purged with N2 (2 x 10 bar) and H2 or D2 (3 x

10 bar). H2 pressure was applied (pressure is given as initial pressure before heating). The

heating block was preheated before the autoclave was placed inside. After the respective reaction time te autoclave was allowed to cool to r.t. and H2 was released. The autoclave

was purged with N2 (3 x 10 bar) before the vials were taken out. Liquids and solutions were

transferred with syringes. Solvents (benzene, 1,2-Cl2C6H4, ClC6H5, CH2Cl2, EtOH, THF, Et2O

and MeCN) were dried and purified following standard procedures. 1,2-Cl2C6D4 (purchased

from Eurisotop) was dried over CaH2, distilled, and stored under argon. Technical grade

solvents for extraction or chromatography (tert-butylmethyl ether, ethyl acetate, cyclohexane, CH2Cl2, n-pentane) were distilled prior to use. C6D6 (purchased from Eurisotop) was stored

over 4 Å molecular sieves or degassed and stored in a glove box over 4 Å molecular sieves. CD2Cl2 (purchased from Eurisotop) was degassed and stored in a glove box over 4 Å

molecular sieves. 1_H, 1_H/13_{C HSQC,} 1_H/13_{C HMBC,} 7_Li, 11_B, 13_C, 19_F, 29_{Si-DEPT and} 1_H/29

Si-HMQC NMR spectra were recorded in CDCl3, C6D6 or CD2Cl2 on Bruker AV400, Bruker

AV500 and Bruker AV700 instruments. Chemical shifts are reported in parts per million (ppm) and are referenced to the residual solvent resonance as the internal standard (C6D5H

δ = 7.16 ppm for 1_{H NMR, C6D6 δ = 128.06 ppm for} 13_{C NMR, CHCl3: δ = 7.26 ppm for} 1_H

NMR, CDCl3: δ = 77.16 ppm for 13C NMR and CHDCl2: δ = 5.32 ppm for 1H NMR and

CD2Cl2: δ = 53.84 ppm for 13C NMR). All other nuclei (7Li, 11B, 19F and 29Si) are referenced in

compliance with the unified scale for NMR chemical shifts as recommended by the IUPAC stating the chemical shift relative to LiCl, BF3∙Et2O, CCl3F and Me4Si.[S1] Data are reported as

follows: chemical shift, multiplicity (s = singlet, d = doublet, t = triplet, m = multiplet, mc =

centrosymmetric multiplet), coupling constant (Hz), and integration. Analytical gas liquid chromatography (GLC) of reaction mixtures and pure substances was performed using a gas chromatograph 430-GC (Varian Inc.). The instrument was equipped with a FactorFour VF-WAXms capillary column (Varian Inc., length: 30 m, inner diameter: 0.25 mm, film thickness of the stationary phase: 0.25 μm), The following temperature program was used for the analysis: carrier gas N2; injection temperature 270°C; detector temperature 270°C; flow rate

4.0 mL/min; temperature program: 40°C start temperature, 20°C/min heating rate to 250°C for 10 min, then 20°C/min heating rate to final temperature 260°C for 5 min. The data was

recorded with the program Galaxie 1.9.302.952 (Varian Inc.) High-resolution mass spectrometry (HRMS) was performed at the Analytical Facility of the Institut für Chemie, Technische Universität Berlin. Optical rotations were measured on a Perkin–Elmer 341 polarimeter with [α]20_{D values reported in 10}1 _{(° cm}2 _g1_{); concentration c is in g/100 mL and}

λ = 589 nm (Na-D-line). Analytical thin-layer chromatography (TLC) was performed on pre-coated aluminium sheets with silica gel 60 with fluorescent indicator from Macherey-Nagel. Flash column chromatography was performed on silica gel 60 (40–63 µm, 230–400 mesh, ASTM) by Grace using the indicated solvents.

2

Experimental Details

2.1 ((1S,2R,5S)-6,6-Dimethylbicyclo[3.1.1]heptan-2-yl)methanol

According to a literature-known procedure,[S2] _{a solution of (–)-β-pinene}[S3] _{(6.0 g, 7.0 mL, 44}

mmol, 1.0 equiv.) in THF (18 mL) was cooled to 0°C. BH3·DMS (90%, 4.6 mL, 44 mmol, 1.0

equiv.) was added dropwise over a period of 1 h, and the resulting solution stirred for 1 h at 0°C. Afterwards, EtOH (21 mL), aqueous NaOH (1.0M, 24 mL), and H2O2 (30%, 11 mL) were

added subsequently, and the resulting suspension was stirred for 30 min at room tempera-ture before heating to 80°C for 2 h. The reaction mixtempera-ture was extracted with tert-butylmethyl ether (3 x 100 mL). The combined organic phases were washed with H2O (3 x 100 mL) and

brine (100 mL) before drying over MgSO4. After removal of all volatiles under reduced

pressure, the residue was purified by flash column chromatography on silica gel using cyclohexane/tert-butylmethyl ether = 4/1 as eluent to afford myrtanol (5.0 g, 73%) as colorless oil.

HRMS (APCI) for C10H17O [M–H]: calculated 153.1274, found 153.1277. 1H NMR (500

MHz, CDCl3): δ/ppm = 0.94 (d, J = 9.5 Hz, 1H), 0.97 (s, 3H), 1.19 (s, 3H), 1.40–1.51 (m, 2H),

1.83–1.98 (m, 4H), 2.00 (mc, 1H), 2.20–2.29 (m, 1H), 2.34–2.41 (m, 1H), 3.57 (mc, 1H). The

OH proton could not be detected. 13_C{1_{H} NMR (126 MHz, CDCl}

3): δ/ppm = 18.9, 23.5, 26.1,

28.1, 33.3, 38.8, 41.6, 43.1, 44.6, 68.0.

2.2 (1S,2R,5S)-6,6-Dimethylbicyclo[3.1.1]heptane-2-carbaldehyde (5)

According to a literature-known procedure,[S2] _{a solution of oxalyl chloride (3.4 mL, 39 mmol,}

was added dropwise, and the resulting mixture was stirred for 5 min. Myrtanol (4.0 g, 26 mmol, 1.0 equiv.) in CH2Cl2 (20 mL) and Et3N (18 mL, 0.13 mol) were added subsequently,

and the reaction mixture was stirred 5 min at –78°C. Afterwards, the reaction was stirred for 1.5 h at room temperature and then quenched by the addition of H2O (150 mL). The phases

were separated, and the organic phase washed with H2O (2 x 100 mL) and brine (100 mL)

before drying over MgSO4. After removal of all volatiles, the aldehyde 5 (4.4 g, quant.) was

stored at –20°C and used without further purification.

HRMS (APCI) for C10H17O [M+H]: calculated 153.1274, found 153.1273. 1H NMR (500

MHz, CDCl3): δ/ppm = 0.71 (s, 3H), 1.21 (s, 3H), 1.25 (d, J = 9.9 Hz, 1H), 1.82–1.97 (m, 4H), 2.22–2.31 (m, 1H), 2.36–2.43 (m, 1H), 2.51–2.57 (m, 1H), 2.70–2.77 (m, 1H), 9.76 (s, 1H). 13_C{1_{H} NMR (126 MHz, CDCl} 3): δ/ppm = 13.4, 23.3, 24.8, 26.9, 29.5, 39.1, 40.8, 42.5, 52.9, 206.1. 2.3 ((1S,2R,5S)-6,6-Dimethylbicyclo[3.1.1]heptan-2-yl)(2,3,5,6-tetrafluorophenyl)meth-anone (9)

A solution of the alcohol 6 (1.7 g, 5.6 mmol, 1.0 equiv.) in CH2Cl2 (60 mL) was cooled to 0°C.

Dess–Martin periodinane (3.6 g, 8.4 mmol, 1.5 equiv.) was added in one portion and the resulting mixture stirred 4 h at room temperature. The reaction was quenched by the addition of H2O (100 mL). The phases were separated, the organic phase washed with H2O (5 x 100

mL) and dried over MgSO4. After removal of all volatiles, the resulting white solid was

removed by filtration through a pad of cotton to afford the ketone 9 (d.r. = 95:5, 1.4 g, 84%) as an orange brown oil without further purification. The diastereomeric ratio was determined by GLC analysis.

HRMS (APCI) for C16H15F4O [M–H]: calculated 299.1054, found 299.1051.

Major diastereomer [(1S,2R,5S)-9]:

1_{H NMR (700 MHz, C}

6D6): δ/ppm = 0.85 (d, J = 9.9 Hz, 1H), 0.88 (s, 3H), 1.06 (s, 3H), 1.55–

1.65 (m, 2H), 1.67–1.71 (m, 1H), 1.76–1.83 (m, 1H), 2.12–2.19 (m, 1H), 2.25–2.31 (m, 1H), 2.34–2.39 (m, 1H), 3.13–3.20 (mc, 1H), 6.08 (mc, 1H). 13C{1H} NMR (176 MHz, C6D6): δ/ppm

= 14.4, 22.7, 25.1, 27.1, 30.8, 39.0, 40.8, 43.0, 54.3, 107.2 (t, J = 23 Hz), 121.3 (t, J = 21 Hz), 142.9 (dm), 146.0 (dm), 196.9. 19_{F NMR (659 MHz, C} 6D6): δ/ppm = –142.4 (mc, 2F), – 137.6 (mc, 2F). Minor diastereomer [(1S,2S,5S)-9]: 1_{H NMR (500 MHz, C} 6D6): δ/ppm = 0.64 (s, 3H) 1.02 (s, 3H), 1.38–1.46 (m, 1H), 1.48 (d, J = 10.6 Hz, 1H), 1.59–1.70 (m, 3H), 2.02 (mc, 1H), 2.21 (mc, 1H), 2.26–2.37 (m, 1H), 3.31 (mc, 1H), 6.06 (mc, 1H). 13C{1H} NMR (176 MHz, C6D6): δ/ppm = 15.0, 20.2, 23.9, 24.2, 26.4, 39.4, 40.5, 42.6, 50.8, 107.2 (t, J = 23 Hz), 121.6 (t, J = 21 Hz), 143.2 (dm), 145.9 (dm), 196.8. 2.4 (1S,2R,5S)-6,6-Dimethyl-2-(1-(2,3,5,6-tetrafluorophenyl)vinyl)bicyclo[3.1.1]heptane (10)

Dimethyltitanocene (0.43M in THF, 5.9 mL, 2.5 mmol, 1.5 equiv.) was added to a solution of the ketone 9 (0.50 g, 1.7 mmol, 1.0 equiv.) in THF (10 mL), and the resulting mixture was heated to 65°C until full conversion as monitored by GLC analysis (18–48 h). The reaction was cooled to room temperature, quenched by the addition of H2O (5.0 mL) and extracted

with tert-butylmethyl ether (2 x 10 mL). The combined organic phases were dried over MgSO4. After removal of all volatiles, the residue was purified by flash column

chromato-graphy on silica gel using n-pentane as eluent to afford the alkene 10 (d.r. = 96:4, 0.28 g, 57%) as a colorless liquid. The diastereomeric ratio was determined by GLC analysis.

HRMS (APCI) for C17H17F4 [M–H]: calculated 297.1261, found 297.1265.

Major diastereomer [(1S,2R,5S)-10]: 1_{H NMR (500 MHz, C} 6D6): δ/ppm = 0.81 (d, J = 9.8 Hz, 1H), 1.00 (s, 3H), 1.15 (s, 3H), 1.48– 1.70 (m, 3H), 1.75–1.88 (m, 2H), 2.18 (mc, 1H), 2.27 (mc, 1H), 3.07 (mc, 1H), 4.95 (d, J = 2.0 Hz, 1H), 5.21 (d, J = 2.2 Hz, 1H), 6.24 (mc, 1H). 13C{1H} NMR (126 MHz, CDCl3): δ/ppm = 19.6, 23.6, 26.2, 28.1, 33.5, 38.7, 41.6, 44.0, 44.6, 104.5 (t, J = 23 Hz), 117.2, 141.7. The ortho- and meta-carbon atom of the aromatic ring could not be detected. 19_F{1_{H} NMR (471}

MHz, C6D6): δ/ppm = –142.3 (dd, J = 13 Hz, J = 24 Hz, 2F), –139.4 (dd, J = 13 Hz, J = 23

Hz, 2F).

Figure 1. Proton correlation signals determined by nOe experiment; R = p-HC6F4.

Minor diastereomer [(1S,2S,5S)-10]: 1_{H NMR (500 MHz, C} 6D6): δ/ppm = 0.70 (s, 3H), 1.11 (s, 3H), 1.38 (d, J = 9.4 Hz, 1H), 1.41– 1.47 (m, 1H), 1.52–1.69 (m, 3H), 1.71–1.76 (m, 1H), 1.99–2.08 (m, 2H), 2.96 (mc, 1H), 4.92 (br s, 1H), 5.23 (br s, 1H), 6.23 (mc, 1H). 13C{1H} NMR (126 MHz, C6D6): δ/ppm = 19.9, 20.8, 23.9, 24.5, 26.9, 39.6, 40.4, 40.6, 44.4, 104.5 (t, J = 23 Hz), 116.8, 123.6 (t), 141.7. The ortho- and meta-carbon atom of the aromatic ring could not be detected. 19_F{1_{H} NMR (471}

MHz, C6D6): δ/ppm = –142.3 (dd, J = 13 Hz, J = 24 Hz, 2F), –139.4 (dd, J = 13 Hz, J = 23

Hz, 2F).

3

Investigation of Substrate-Controlled Hydrogenation of 10

F F F F F F F F catalyst (5.0 mol%) ligand (20 mol%) H2 solvent temp.

entry catalyst ligand H2

-pressure solvent temp.

1 2 3 4 5 conv.[2] d.r.[3]

[Rh(cod)Cl]2 25 bar _benzeneEtOH/ 10 °C 85% 86:14

[Rh(cod)Cl]2 25 bar _benzeneEtOH/ 10 °C 7% –

[Rh(cod)Cl]2 25 bar _benzeneEtOH/ 10 °C >99% 89:11

[Rh(cod)Cl]2 P(2-MeC6H5)3 25 bar _benzeneEtOH/ 10 °C 0 –

P(4-MeOC6H5)3

P(4-CF3C6H5)3

P(4-tBuC6H5)3

(Ph3P)3RhCl – 25 bar _benzeneEtOH/ 10 °C 20% 90:10

6 (Ph3P)3RhCl – 25 bar 1,4-dioxane 10 °C 70% 85:15 8 (Ph3P)3RhCl – 25 bar benzene 10 °C >99% 88:12 7 (Ph3P)3RhCl – 30 bar benzene 30 °C >99% 87:13 H 10 11 H *  

[1] All reactions were performed in a 0.15 mmol scale respective to alkene 10. [2] Conversion was determined by GLC analysis. [3] The d.r. was determined by 1_{H NMR and GLC analysis.}

4

Investigation of Catalyst-Controlled Hydrogenation of 10

[1] All reactions were performed in a 0.15 mmol scale respective to alkene 10. [2] The conversion was determined by GLC analysis. [3] The d.r. was determined by 1_{H NMR and GLC analysis.}

5

Deuteration Experiments for the Investigation of Triphenylmethane

Formation

5.1 (1S,2S,5S)-6,6-Dimethyl-2-(1-(2,3,5,6-tetrafluorophenyl)ethyl-1,2-d2

)bicyclo-[3.1.1]heptane (11-d2)

In a glass vial the alkene 10 (45 mg, 0.15 mmol, 1.0 equiv.) and (Ph3P)3RhCl (6.9 mg, 7.5

mol, 5.0 mol%) were placed under a nitrogen atmosphere and dissolved in degassed benzene (2.0 mL). The reaction vessel was transferred to an autoclave, pressurized with D2

(30 bar) and stirred for 18 h at 30°C (for further details, see section General Information). Afterwards the vial was removed from the autoclave and filtered through a plug of silica. Removal of all volatiles under reduced pressure gave the alkane 11-d2 (d.r. = 85:15, 45 mg,

quant.) as a colorless liquid. The diastereomeric ratio was determined by GLC analysis.

1_{H NMR (500 MHz, C} 6D6): δ/ppm = 0.72 (d, J = 9.7 Hz, 1H), 1.01 (s, 3H), 1.03 (s, 3H), 1.11 (br s, 2H), 1.33–1.43 (m, 1H), 1.51 (mc, 1H), 1.68–1.90 (m, 4H), 2.17 (mc, 1H), 2.35–2.44 (m, 1H), 6.18 (mc, 1H). 2H NMR (77 MHz, C6D6): δ/ppm = 0.98–1.15 (m), 3.05–3.22 (m). 13C{1H} NMR (126 MHz, C6D6): δ/ppm = 17.0, 21.8, 22.9, 26.8, 28.3, 34.2, 36.8 [Determined by 1_H/13_{C HMBC NMR (500/175 MHz, C6D6)], 38.6, 41.4, 44.9, 45.1, 103.6 (t, J = 22 Hz), 145.4} [Determined by 1_H/13_{C HMBC NMR (500/175 MHz, C} 6D6)], 147.2 [Determined by 1H/13C HMBC NMR (500/175 MHz, C6D6)]. 19F NMR (471 MHz, C6D6): δ/ppm = –144.7–[–140.8] (m, 2F), –139.6 (br s, 2F).  

5.2 Lithium tetrakis(4-(1-((1S,2S,5S)-6,6-dimethylbicyclo[3.1.1]heptan-2-yl)ethyl-1,2-d2)-2,3,5,6-tetrafluorophenyl)borate ([Li]+[4-d2]–)

To a solution of alkane 11-d2 (d.r. = 85:15, 0.35 g, 1.2 mmol, 5.0 equiv.) in Et2O (22 mL) was

added dropwise nBuLi (2.7M in hexane, 0.42 mL, 1.1 mmol, 4.4 equiv.) at –78°C and the resulting mixture stirred for 3 h. Afterwards BCl3 (1M in heptane, 0.23 mL, 0.23 mmol, 1.0

equiv.) was added dropwise and the solution was allowed to warm up to room temperature overnight slowly. The reaction was quenched by addition of H2O (20 mL) and extracted with

CH2Cl2 (2 x 10 mL). After removal of all volatiles the residue was purified by flash column

chromatography on silica gel using subsequent CH2Cl2 (200 mL) and acetone (500 mL) as

eluent. The lithium borate [Li]+_[4-d

2]– was obtained as a white solid and directly used in the

subsequent salt metathesis reaction.

5.3 Sodium tetrakis(4-(1-((1S,2S,5S)-6,6-dimethylbicyclo[3.1.1]heptan-2-yl)ethyl-1,2-d2)-2,3,5,6-tetrafluorophenyl)borate ([Na]+[4-d2]–)

To a solution of the lithium borate [Li]+_[4-d

2]– in CH2Cl2 (5.0 mL) was added a saturated

aqueous solution of NaCl (5.0 mL) and the two-phase mixture stirred overnight at room temperature rapidly. Afterwards the phases were separated, the organic phase was dried over Na2SO4 and all volatiles removed under high vacuum (130°C/10–3mbar). The sodium

borate [Na]+_[4-d

2]– (0.28 g, 94% over two steps) was obtained as a white solid.

HRMS (APCI) for C68H68D8BF16– [M]–: calculated 1215.6292, found 1215.6276. 1H NMR (500

MHz, C6D6): δ/ppm = 0.71–0.80 (br m, 4H), 1.01–1.12 (br m, 24H), 1.12–1.23 (br m, 8H),

1.42–1.53 (br m, 4H), 1.62–1.74 (br m, 4H), 1.74–1.96 (br m, 16H), 2.13–2.24 (br m, 4H), 2.42–2.54 (br m, 4H). 11_B{1_{H} NMR (160 MHz, C}

6D6): δ/ppm = –15.8. 13C{1H} NMR (126

MHz, C6D6): δ/ppm = 17.6, 22.2, 23.0, 27.0, 28.3, 34.2, 36.8, 38.6, 41.5, 45.2, 45.4, 120.1 (t,

J = 18 Hz). The ortho- and meta carbon atoms of the aromatic rings as well as the carbon atoms of the C–B bonds could not be detected. 19_{F NMR (471 MHz, C}

6D6): δ/ppm = –150.8–

[–143.5] (br m, 8F), –139.0–[–130.7] (br m, 8F).

5.4 Triphenylmethylium tetrakis(4-(1-((1S,2S,5S)-6,6-dimethylbicyclo[3.1.1]heptan-2-yl)ethyl-1,2-d2)-2,3,5,6-tetrafluorophenyl)borate ([Tr]+[4-d2]–)

The borate [Na]+_[4-d

2]– (0.10 g, 80 mol, 1.0 equiv.) and triphenylmethyl chloride (0.11 g,

0.40 mmol, 5.0 equiv.) were suspended in n-hexane (6.0 mL) and stirred 2.5 h at room temperature. The suspension was filtered under nitrogen and the remaining solid was washed with n-hexane (6 x 3.0 mL). The orange solid was redissolved in CH2Cl2 (2.0 mL)

and then dried under high vacuum (50°C/10–3 _{mbar). The trityl salt [Tr]}+_[4-d

2]– (86 mg, 0.058

mmol, 72%) was obtained as an orange solid with triphenylmethane (3.0 mg, 0.011 mmol, 14%) as byproduct. The amount of triphenylmethane was determined in 1_{H NMR by}

integration of the baseline separated signals at δ 7.64 ppm and δ 7.13 ppm.

HRMS (APCI) for C68H68D8BF16– [M]–: calculated 1215.6292, found 1215.6290. HRMS

(APCI) for C19H15+ [M]+: calculated 243.1168, found 243.1167. 1H NMR (700 MHz, CD2Cl2):

δ/ppm = 0.74–0.80 (br m, 4H), 1.02 (br s, 24H), 1.19 (br s, 8H), 1.40–1.57 (br m, 4H), 1.57– 1.67 (br m, 4H), 1.78–1.90 (br m, 8H), 1.93–2.08 (br m, 8H), 2.17–2.26 (br m, 4H), 2.29–2.40 (br m, 4H), 7.64 (dd, J = 8.5 Hz, J = 1.3 Hz, 6H), 7.84 (mc, 6H), 8.24 (tt, J = 7.5 Hz, J = 1.3 Hz, 3H). 2_{H NMR (107 MHz, CD} 2Cl2): δ/ppm = 1.22 (br s), 3.12 (br s). 11B{1H} NMR (161 MHz, CD2Cl2): δ/ppm = –16.5. 13C{1H} NMR (176 MHz, CD2Cl2): δ/ppm = 17.7 (mc), 22.2, 22.9, 27.1, 28.3, 34.3, 36.1–36.7, 38.7, 41.6, 45.1, 45.4, 119.0 (t, J = 17 Hz), 131.0, 140.3, 143.0, 144.0, 211.1. The ortho- and meta carbon atoms of the aromatic rings as well as the carbon atoms of the C–B bonds could not be detected. 19_{F NMR (471 MHz, CD}

2Cl2): δ/ppm =

–151.3–[–145.6] (br m, 8F), –134.1 (br s, 8F).

6

Charaterization Data of Mukaiyama Aldol Products

nBuLi (2.5M in hexane, 4.4 mL, 12 mmol, 1.1 equiv.) was added dropwise to a solution of freshly distilled N,N-diisopropylamine (1.7 mL, 12 mmol, 1.2 equiv.) in THF (20 mL) at 0°C. The resulting solution was stirred for 20 min at 0 °C and then cooled to 78 °C. Ethyl acetate (1.0 mL, 10 mmol, 1.0 equiv.) was added dropwise over 10 min, and the mixture stirred for additional 30 min. DMPU (3 mL) was then added dropwise, followed by a solution of tert-butyldimethylsilyl chloride (1.8 g, 12 mmol, 1.2 equiv.) in THF (3.0 mL). The reaction mixture was stirred for 30 min at 78 °C and then allowed to warm to room temperature overnight. The volatiles were removed under reduced pressure, and the residue resolved in n-pentane (80 mL). The organic phase was washed successively with water (30 mL), saturated aqueous CuSO4 solution (30 mL), saturated aqueous NaHCO3 solution (30 mL), and brine

(30 mL). After removal of volatiles under reduced pressure, the title compound was purified by distillation (bp 72 °C at 23 mbar) to give 18 (1.1 g, 54%) as colorless oil.

1_{H NMR (400 MHz, CDCl} 3): δ/ppm = 0.17 (s, 6H), 0.93 (s, 9H), 1.29 (t, 3J = 7.0 Hz, 3H), 3.06 (d, J = 2.3 Hz, 1H), 3.22 (d, J = 2.3 Hz, 1H), 3.75 (q, J = 7.1 Hz, 2H). 13_C{1_{H} NMR (126} MHz, CDCl3): δ/ppm = 4.4, 14.5, 18.3, 25.8, 60.6, 63.5, 161.4. 29Si DEPT NMR (99 MHz, CDCl3): δ/ppm = 21.8. 6.2 Ethyl 3-((tert-butyldimethylsilyl)oxy)-3-phenylpropanoate (20)  

In a glovebox, the trityl salt [Me_Tr]+_[4]– _{(41 mg, 0.021 mmol, 10 mol%) is placed in a}

medium-sized vial, dissolved in CH2Cl2 (1 mL), transferred to a fume hood, and connected to a

benzaldehyde (19, 21 mg, 0.20 mmol, 1.0 equiv.) in CH2Cl2 (0.5 mL) was added. The mixture

was stirred for 15 min, and a solution of 1-(tert-butyldimethylsilyloxy)-1-ethoxyethylen (18, 45 mg, 0.22 mmol, 1.1 equiv.) in CH2Cl2 (0.7 mL) was then added dropwise over a period of 2 h.

The reaction mixture was stirred for additional 4.5 h at 78°C and then quenched by the addition of aqueous saturated NaHCO3 solution (30 mL). The aqueous phase was extracted

with CH2Cl2 (3 x 10 mL), the combined organic phases dried over MgSO4, and the solvent

removed under reduced pressure. Purification of the residue by flash column chromatography on silica gel using cyclohexane/tert-butylmethyl ether = 50/1 as eluent afforded the silylether 20 (35 mg, 55%) as a yellow oil.

1_{H NMR (500 MHz, CDCl} 3): δ/ppm = 0.18 (s, 3H), 0.02 (s, 3H), 0.85 (s, 9H), 1.25 (t, 3J = 7.1 Hz, 3H), 2.54 (dd, J = 14.5, 4.2 Hz, 1H), 2.72 (dd, J = 14.6, 9.3 Hz, 1H), 4.13 (mc, 2H), 5.15 (dd, J = 9.1, 4.1 Hz, 1H), 7.227.26 (m, 1H), 7.297.37 (m, 4H). 13_C{1_{H} NMR (126 MHz,} CDCl3): δ/ppm = 5.2, 4.6, 14.3, 18.2, 25.8, 46.6, 60.6, 72.4, 126.0 (2C), 127.6, 128.4 (2C), 144.3 171.4. 29_{Si DEPT NMR (99 MHz, CDCl} 3): δ/ppm = 19.9.

The enantiomeric excess was determined by HPLC analysis on a chiral stationary phase of the corresponding alcohol (Daicel Chiralcel OD-H column, 20 °C, n-heptane/i-PrOH = 96/4, flow rate 0.50 mL/min, λ = 254 nm): tR = 29.8 min, tR = 45.5 min. Deprotection of 17 (20 mg,

0.065 mmol) in THF (1 mL) by the addition of aqueous HCl (1 M, 1 mL) gave the product as a yellow oil (11 mg) without further purification.

1_{H NMR (500 MHz, CDCl} 3): δ/ppm = 1.27 (t, J = 7.1 Hz, 3H), 2.692.80 (m, 2H), 4.19 (q, J = 7.2 Hz, 2H), 5.14 (dd, J = 3.9 Hz, 8.9 Hz, 1H), 7.277.31 (m, 1H), 7.347.40 (m, 4H). 13_C{1_H} NMR (126 MHz, CDCl3): δ/ppm = 14.3, 43.5, 61.0, 70.5, 125.8 (2C), 128.0, 128.7 (2C), 142.6, 172.6. 6.3 tert-Butyl((1-ethoxyvinyl)oxy)dimethylsilan (21)  

To a solution of N,N-diisopropylamine (4.8 mL, 34 mmol, 1.3 equiv.) in THF (20 mL) was added nBuLi (2.67M in hexane, 12 mL, 31 mmol, 1.2 equiv.) dropwise at 0°C and the mixture was stirred for 30 min. Methyl isobutyrate (3.0 mL, 26 mmol, 1.0 equiv.) was added and the solution stirred for an additional hour at 0°C before trimethylsilyl chloride (3.0 mL, 26 mmol,

1.0 equiv.) was added. After stirring for 1 h at 0°C the solution was filtered, all volatiles removed under reduced pressure and the residue taken up in Et2O (30 mL). The suspension

was filtered again, the volatiles removed again under reduced pressure. Purification by distillation (bp. 42°C at 13 mbar) of the residue afforded the silylketene acetal 21 (2.0 g, 44%) as a colorless liquid. 1_{H NMR (500 MHz, C} 6D6): δ/ppm = 0.18 (s, 9H, Si(CH3)3), 1.66 (s, 3H, 4-CH3-a), 1.73 (s, 3H, 4-CH3-b), 3.33 (s, 3H, H-1). 1H/29Si-HMQC (500/99 MHz, 298K, optimized on J = 7.0 Hz): δ/ppm = 0.18/18.6. 6.4 rac-Ethyl 3-hydroxy-2,2-dimethyl-3-phenylpropanoat (23)  

N,N-Diisopropylamine (1.3 g, 13 mmol, 1.3 equiv.) was suspended in THF (44 mL) and cooled to –78°C. nBuLi (2.67M in hexane, 4.5 mL, 12 mmol, 1.2 equiv.) was added dropwise and the mixture stirred for 30 min at 0°C. The resulting solution was cooled to –78°C, methyl isobutyrate was added, and the mixture was stirred for 1 h before a solution of 2-naphth-aldehyde (22, 1.9 g, 12 mmol, 1.2 equiv.) in THF (7 mL) was added dropwise. The mixture was warmed to room temperature and stirred for 1.5 h. The reaction was quenched by the addition of saturated aqueous solution of NH4Cl (10 mL) and extracted with tert-butylmethyl

ether (2 x 15 mL). The combined organic phases were dried over MgSO4. After removal of all

volatiles, the residue was purified by flash column chromatography on silica gel using cyclo-hexane/tert-butylmethy ether = 5/1 as eluent to afford the title compound 23 (1.8 g, 70%) as colorless solid.

HRMS (APCI) for C16H17O2+ [M–OH]+: calculated 241.1229, found 241.1228. 1H NMR (500

MHz, CDCl3): δ/ppm = 1.16 (s, 3H, 3-CH3), 1.20 (s, 3H, 3-CH3), 3.25 (d, 3JH,H = 4.5 Hz, 1H,

OH), 3.74 (s, 3H, H-1), 5.07 (d, 3_J

H,H = 4.2 Hz, 1H, H-4), 7.41–7.52 (m, 3H, H-Ar), 7.74–7.87

(m, 4H, H-Ar). 13_C{1_{H} NMR (126 MHz, CDCl}

3): δ/ppm = 19.3 (3-CH3), 23.3 (3-CH3), 48.1

3), 52.3 1), 78.9 4), 125.8 Ar), 126.1 Ar), 126.2 Ar), 126.8 Ar), 127.4 (C-Ar), 127.7 (C-(C-Ar), 128.2 (C-(C-Ar), 133.0 (C-10ꞌ)*_{, 133.1 (C-6ꞌ)}*_{, 137.6 (C-5), 178.4 (C-2).}

6.5 Dimethyl 3,3'-oxybis(2,2-dimethyl-3-(naphthalen-2-yl)propanoate)

  To a solution of sodium borate [Na]+_[4]– _{(24 mg, 0.020 mmol, 10 mol%) and}

2-naphth-aldehyde (22, 31 mg, 0.20 mmol, 1.0 equiv.) in toluene (2.0 mL) was added at –80°C the silylketene acetal 21 (44 mg, 0.25 mmol, 1.25 equiv.) and trimethylsilyl chloride (0.05 mL). The reaction was stirred for 22 h at –80°C (full conversion of aldehyde determined by GLC analysis) and then for 30 min at room temperature (full conversion of silyl ether to alcohol determined by GLC analysis). The reaction was quenched by the addition of saturated aqueous NaHCO3 solution (3.0 mL). The organic phase was dried over Na2SO4. During

workup formation of the shown ether was determined by GLC. After removal of all volatiles the ether was observed exclusively.

HRMS (APCI) for C32H35O5+ [M+H]+: calculated 499.2479, found 499.2484. Spectroscopic

data of one diastereomer: 1_{H NMR (500 MHz, CDCl}

3): δ/ppm = 0.98 (s, 3H, 3-CH3), 1.29 (s, 3H, 3-CH3), 3.75 (s, 3H, H-1), 4.94 (s, 1H, H-4), 7.12 (mc, 1H, H-12), 7.32–7.37 (m, 1H, H-8)*, 7.37–7.42 (m, 2H, H-6, H9*_{), 7.46–7.52 (m, 2H, H-10}*_{, H-11), 7.70 (d,} 3_J H,H = 8.2 Hz, 1H, H-7). 13_C{1_{H} NMR (126 MHz, CDCl} 3): δ/ppm = 19.6 (3-CH3), 22.9 (3-CH3), 48.6 3), 52.0 (C-1), 86.0 (C-4), 125.8 (C-8)*_{, 125.9 (C-9)}*_{, 126.7 (C-10)}*_{, 126.9 12), 127.5 7), 128.0} (C-11), 128.2 (C-6), 132.6 (C-6ꞌ), 132.9 (C-10ꞌ), 136.1 (C-5), 177.2 (C-2).

The enantiomeric excess of 23 was determined by HPLC analysis of an aliquot of the reaction mixture, filtered over a plug of silica (Daicel Chiralcel OD-H column, 20 °C, n-heptane/i-PrOH = 95/5, flow rate 1.00 mL/min, λ = 254 nm): tR = 23.1 min, tR = 26.7 min.

7

Characterization Data of Diels

Alder Products

7.1 endo-Phenyl-(3-phenylbicyclo[2.2.2]oct-5-en-2-yl)methanone (15)

In a glovebox, the trityl salt [Me_Tr]+_[4]– _{(23 mg, 13 µmol, 5.0 mol%) and chalcone (13, 52 mg,}

0.25 mmol, 1.0 equiv.) were placed in a medium-sized vial and dissolved in benzene (0.80 mL). Cyclohexa-1,3-diene (14, 40 mg, 50 µL, 0.50 mmol, 2.0 equiv.) was added, and the mixture was maintained for 17 h at room temperature. The reaction was quenched by the addition of saturated aqueous NaHCO3 solution (5.0 mL), the phases were separated, and

the aqueous phase extracted with tert-butylmethyl ether (2 × 10 mL). The combined organic phases were dried over Na2SO4, and the volatiles removed under reduced pressure.

Purification of the residue by flash column chromatography on silica gel using cyclohexane/tert-butylmethyl ether = 70/1 as eluent afforded the title compound 15 (58 mg, 80%). 1_{H NMR (500 MHz, CDCl} 3): δ/ppm = 1.08–1.17 (m, 1H), 1.49 (mc = 1H), 1.79–1.87 (m, 1H), 1.87–1.94 (m, 1H), 2.64–2.70 (m, 1H), 2.94–3.01 (m, 1H), 3.45–3.50 (m, 1H), 3.78–3.83 (m, 1H), 6.11 (mc, 1H), 6.56 (mc, 1H), 7.18–7.23 (m, 1H) 7.27–7.34 (m, 4H) 7.37–7.42 (m, 2H), 7.48–7.53 (m, 1H), 7.85–7.89 (m, 2H). 13_C{1_{H} NMR (101 MHz, CDCl} 3): δ/ppm  18.6, 26.6, 34.7, 36.6, 44.8, 51.1, 126.3, 128.3, 128.57 (3C), 128.62, 130.8, 132.8, 136.4, 136.5, 143.0, 200.9. HPCL (Daicel Chiralcel OD-H, 20 °C, n-heptane/i-PrOH = 97/3, flow rate 0.65 mL/min,  = 254 nm): tR = 13.0 min, tR = 15.2 min.

7.2 endo-2-Methylbicyclo[2.2.2]oct-5-ene-2-carbaldehyde (17)

In a glovebox, the trityl salt [Me_Tr]+_[4]– _{(13 mg, 7.0 µmol 5.0 mol%) is placed in a medium}

equiv.) and cyclohexa-1,3-diene (14, 14 mg, 0.14 mmol, 1.0 equiv.) were placed in a second medium sized vial. Both vials were transferred to a fume hood, connected to a nitrogen– vacuum manifold and cooled to 20 °C. The trityl solution was transferred to the substrates and the mixture was stirred for 23 h at 20 °C. Filtration over a plug of silica gave the product 17 (9.7 mg, 46%) as slightly yellow oil.

1_{H NMR (400 MHz, CDCl}

3): δ/ppm = 1.15 (s, 3H), 1.161.32 (m, 3H), 1.491.58 (m, 1H),

1.90 (dddd, J = 12.6 Hz, J = 9.5, J = 3.0, J = 2.5 Hz, 1H), 2.01 (ddd, J = 13 Hz, J = 9.6 Hz, J = 3.2 Hz, 1H), 2.48 (mc, 1H), 2.60 (mc, 1H), 6.25 (mc, 2H), 9.32 (s, 1H). 13C{1H} NMR (101

MHz, CDCl3): δ/ppm = 20.3, 21.3, 25.2, 30.6, 35.6, 36.2, 50.1, 133.6, 135.2, 205.8.

The enantiomeric excess was determined after reduction of 17 with NaBH4 to the

corresponding alcohol, conversion to the (S)-MTPA ester derivate,[S5] _{and integration of the}

baseline-separated 1_{H NMR resonances (400 MHz, CDCl3): δ/ppm = 3.99 (d, J = 10.4 Hz,}

1H), (3.89, d, J = 10.4 Hz, 1H), 3.83 (d, J = 10.4 Hz, 1H), 3.72 (d, J = 10.4 Hz, 1H).

8

NMR Spectra of All Compounds

  10.0 9.0 8.0 7.0 6.0 5.0 4.0 3.0 2.0 1.0 0.0 ppm 0.92 0.94 0.97 1.19 1.40 1.51 1.83 1.98 1.99 2.04 2.20 2.29 2.34 2.41 3.53 3.55 3.55 3.57 3.57 3.59 3.60 3.61 1. 03 3. 00 3. 15 2. 32 4. 17 1. 00 1. 00 1. 04 2. 01 ((1S,2R,5S)-6,6-Dimethylbicyclo[3.1.1]heptan-2-yl)methanol 1_{H NMR (500 MHz, CDCl} 3):

  210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm 18.91 23.47 26.14 28.12 33.29 38.79 41.64 43.04 44.63 67.98 13_C{1_{H} NMR (126 MHz, CDCl} 3):

  10.0 9.0 8.0 7.0 6.0 5.0 4.0 3.0 2.0 1.0 0.0 ppm 0.71 1.21 1.24 1.26 1.82 1.97 2.22 2.31 2.36 2.43 2.51 2.57 2.70 2.77 9.76 3.00 3.10 1.20 4.21 1.07 1.10 0.91 0.87 0.76

(1S,2R,5S)-6,6-Dimethylbicyclo[3.1.1]heptane-2-carbaldehyde (5)

  210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm 13.41 23.30 24.76 26.90 29.53 39.06 40.79 42.51 52.86 206.08 13_C{1_{H} NMR (126 MHz, CDCl} 3):

  10.0 9.0 8.0 7.0 6.0 5.0 4.0 3.0 2.0 1.0 0.0 ppm 0.74 0.76 1.01 1.03 1.06 1.11 1.18 1.22 1.53 1.64 1.69 1.77 1.82 2.29 2.36 2.39 2.44 2.47 2.57 4.95 4.97 6.23 1.02 3.00 2.33 4.25 1.90 1.12 1.05 1.20 0.94 1.00 0.90 0.86

((1S,2R,5S)-6,6-Dimethylbicyclo[3.1.1]heptan-2-yl)(2,3,5,6-tetrafluorophenyl)methanol (6, major diastereomer)

1_{H NMR (500 MHz, C} 6D6):

tBuOMe

tBuOMe

  210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm 18.24 22.93 26.34 27.10 27.25 28.18 33.41 38.68 41.52 42.39 46.56 69.40 104.68 104.86 105.04 123.36 123.48 123.60 143.74 145.34 145.74 147.31 13

_C{

_{H} NMR (126 MHz, C}

_D

_):

-105 -110 -115 -120 -125 -130 -135 -140 -145 -150 -155 -160 -165 -170 -175 ppm -143.51 -143.48 -143.46 -143.43 -139.42 -139.39 -139.37 -139.34 19

_F{

_{H} NMR (471 MHz, C}

_D

_):

  10.0 9.0 8.0 7.0 6.0 5.0 4.0 3.0 2.0 1.0 0.0 ppm 0.89 0.95 1.12 1.27 1.30 1.53 1.89 1.97 2.43 2.50 2.63 5.06 6.99 1.20 3.64 4.01 1.29 1.45 2.71 2.30 1.13 1.08 1.00

((1S,2R,5S)-6,6-Dimethylbicyclo[3.1.1]heptan-2-yl)(2,3,5,6-tetrafluorophenyl)methanol (6, minor diastereomer)

1_{H NMR (500 MHz, C} 6D6):

tBuOMe

210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm 19.91 23.00 26.35 27.93 33.58 38.58 41.41 43.81 46.81 70.99 104.72 104.90 105.08 123.53 123.65 123.77 143.77 145.15 145.80 147.13 13_C{1_{H} NMR (126 MHz, C} 6D6):

  -105 -110 -115 -120 -125 -130 -135 -140 -145 -150 -155 ppm -143.51 -143.48 -143.46 -143.43 -139.41 -139.39 -139.37 -139.34 19_F{1_{H} NMR (471 MHz, C} 6D6):

  10.0 9.0 8.0 7.0 6.0 5.0 4.0 3.0 2.0 1.0 0.0 ppm 0.73 0.75 1.11 1.13 1.18 1.21 1.53 1.63 1.70 1.80 2.03 2.25 2.32 2.38 3.07 6.13 6.14 6.15 6.16 6.16 6.16 6.17 6.18 6.19 7.17 1.07 3.09 4.92 1.18 2.02 2.93 1.20 1.11 1.16 1.00 1.13

O

-(((1S,2R,5S)-6,6-Dimethylbicyclo[3.1.1]heptan-2-yl)(2,3,5,6-tetrafluorophenyl)-methyl) S-methyl carbonodithioate (7)

1_{H NMR (500 MHz, C} 6D6):

  210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm 17.38 18.89 22.79 26.11 27.92 33.15 38.55 41.34 42.55 43.34 78.65 106.10 106.28 106.46 118.35 118.47 118.59 144.26 145.15 146.24 147.13 13_C{1_{H} NMR (126 MHz, C} 6D6):

-105 -110 -115 -120 -125 -130 -135 -140 -145 -150 -155 -160 -165 -170 -175 ppm -141.04 -140.57 -138.68 -138.65 -138.63 -138.60 19_F{1_{H} NMR (471 MHz, C} 6D6):

  10.0 9.0 8.0 7.0 6.0 5.0 4.0 3.0 2.0 1.0 0.0 ppm 0.68 0.70 1.07 1.14 1.31 1.47 1.60 1.73 1.77 1.88 2.15 2.25 2.52 2.64 6.22 1.00 3.06 3.01 1.24 3.11 2.05 2.01 1.99 0.92

(1S,2S,5S)-6,6-Dimethyl-2-(2,3,5,6-tetrafluorobenzyl)bicyclo[3.1.1]heptane (8)

210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm 22.02 22.95 26.56 28.17 30.05 33.89 38.88 41.45 41.56 45.34 103.44 103.62 103.80 120.91 121.06 121.21 144.09 144.48 144.88 145.29 146.04 146.38 146.90 147.30 13_C{1_{H} NMR (126 MHz, C} 6D6):

  10.0 9.0 8.0 7.0 6.0 5.0 4.0 3.0 2.0 1.0 0.0 ppm 0.84 0.86 0.88 1.06 1.53 1.66 1.71 1.75 1.83 2.15 2.28 2.36 3.11 3.20 6.07 1.16 3.00 3.21 2.33 1.18 1.09 1.09 1.04 0.99 1.00 0.90

((1S,2R,5S)-6,6-Dimethylbicyclo[3.1.1]heptan-2-yl)(2,3,5,6-tetrafluorophenyl)methanone (9, major diastereomer)

1_{H NMR (700 MHz, C} 6D6):

210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm 14.42 22.69 25.11 27.10 30.82 38.97 40.85 43.03 54.31 107.04 107.17 107.30 121.32 142.24 143.64 145.28 146.70 196.87 13_C{1_{H} NMR (176 MHz, C} 6D6):

  -105 -110 -115 -120 -125 -130 -135 -140 -145 -150 -155 -160 -165 -170 -175 ppm

-142.40

-137.60

19_F{1_{H} NMR (659 MHz, C} 6D6):

  10.0 9.0 8.0 7.0 6.0 5.0 4.0 3.0 2.0 1.0 0.0 ppm 0.64 1.02 1.38 1.46 1.47 1.49 1.59 1.70 2.02 2.20 2.21 2.22 2.26 2.37 3.29 3.31 3.33 6.03 6.04 6.04 6.06 6.06 6.06 6.07 6.08 6.09 3.08 3.10 1.39 1.27 3.61 1.17 1.06 1.36 1.02 1.00

((1S,2S,5S)-6,6-Dimethylbicyclo[3.1.1]heptan-2-yl)(2,3,5,6-tetrafluorophenyl)methanone (9, minor diastereomer)

1_{H NMR (500 MHz, C} 6D6):

  210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm 15.00 20.17 23.86 24.21 26.36 39.40 40.46 42.64 50.78 107.04 107.22 107.40 121.57 142.22 144.19 144.96 146.94 196.76 13_C{1_{H} NMR (126 MHz, C} 6D6):

  10.0 9.0 8.0 7.0 6.0 5.0 4.0 3.0 2.0 1.0 0.0 ppm 0.80 0.82 1.00 1.15 1.48 1.70 1.75 1.88 2.18 2.27 3.06 3.07 3.09 4.94 4.95 5.21 5.22 6.24 1.20 3.20 3.29 3.66 2.17 1.04 1.08 1.04 1.09 1.10 1.00

(1S,2R,5S)-6,6-Dimethyl-2-(1-(2,3,5,6-tetrafluorophenyl)vinyl)bicyclo[3.1.1]heptane (10, major diastereomer)

1_{H NMR (500 MHz, C} 6D6):

  210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm 19.60 23.56 26.22 28.11 33.48 38.71 41.59 44.03 44.62 104.31 104.49 104.67 117.22 141.66 13_C{1_{H} NMR (126 MHz, C} 6D6):

-105 -110 -115 -120 -125 -130 -135 -140 -145 -150 -155 -160 -165 -170 -175 ppm -142.32 -142.29 -142.27 -142.25 -139.49 -139.46 -139.44 -139.41 19_F{1_{H} NMR (659 MHz, C} 6D6):

  10.0 9.0 8.0 7.0 6.0 5.0 4.0 3.0 2.0 1.0 0.0 ppm 0.70 1.11 1.37 1.39 1.41 1.47 1.52 1.69 1.71 1.76 1.99 2.08 2.95 2.96 2.98 4.92 5.23 5.24 6.23 3.11 3.29 1.24 1.15 3.97 1.20 2.29 1.07 1.05 1.03 1.00

(1S,2S,5S)-6,6-Dimethyl-2-(1-(2,3,5,6-tetrafluorophenyl)vinyl)bicyclo[3.1.1]heptane (10, minor diastereomer)

1_{H NMR (500 MHz, C} 6D6):

210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm 19.91 20.78 23.90 24.45 26.86 39.56 40.45 40.62 44.38 104.36 104.55 104.73 116.77 123.57 141.67 13_C{1_{H} NMR (126 MHz, C} 6D6):

  -105 -110 -115 -120 -125 -130 -135 -140 -145 -150 -155 -160 -165 -170 -175 ppm -142.20 -142.17 -142.15 -142.12 -139.41 -139.39 -139.37 -139.34 19_F{1_{H} NMR (659 MHz, C} 6D6):

  10.0 9.0 8.0 7.0 6.0 5.0 4.0 3.0 2.0 1.0 0.0 ppm 0.71 0.73 1.01 1.03 1.12 1.14 1.33 1.44 1.51 1.68 1.90 2.17 2.34 2.46 3.21 6.18 1.41 3.10 3.01 3.48 1.39 1.11 4.97 1.04 1.33 1.00 1.02

(1S,2S,5S)-6,6-Dimethyl-2-(1-(2,3,5,6-tetrafluorophenyl)ethyl)bicyclo[3.1.1]heptane (11)

  210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm 17.39 21.87 22.90 26.81 28.29 34.22 37.29 38.65 41.45 45.06 45.11 103.46 103.65 103.83 125.79 125.91 126.04 13_C{1_{H} NMR (126 MHz, C} 6D6):

-105 -110 -115 -120 -125 -130 -135 -140 -145 -150 -155 -160 -165 -170 -175 ppm -144.61 -140.99 -140.18 -139.16 19_F{1_{H} NMR (471 MHz, C} 6D6):

  10.0 9.0 8.0 7.0 6.0 5.0 4.0 3.0 2.0 1.0 0.0 ppm 0.71 0.73 1.01 1.03 1.11 1.33 1.43 1.47 1.54 1.68 1.91 2.13 2.21 2.35 2.44 6.18 1.02 6.23 2.02 1.21 0.95 4.55 1.00 1.10

(1S,2S,5S)-6,6-Dimethyl-2-(1-(2,3,5,6-tetrafluorophenyl)ethyl-1,2-d

)bicyclo-[3.1.1]heptane (11-d

)

10.0 9.0 8.0 7.0 6.0 5.0 4.0 3.0 2.0 1.0 0.0 ppm

1.23

1.00

2_{H NMR (77 MHz, C} 6D6):

  210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm 17.02 21.81 22.88 26.80 28.29 34.20 38.63 41.44 44.92 45.10 103.64 13_C{1_{H} NMR (126 MHz, C} 6D6):

-105 -110 -115 -120 -125 -130 -135 -140 -145 -150 -155 -160 -165 -170 -175 ppm -144.72 -140.83 -139.63 19_F{1_{H} NMR (471 MHz, C} 6D6):

  10.0 9.0 8.0 7.0 6.0 5.0 4.0 3.0 2.0 1.0 0.0 ppm 0.85 0.87 1.14 1.19 1.57 1.67 1.80 1.94 1.95 2.02 2.24 2.37 2.65 2.76 1.07 2.83 2.88 1.02 3.96 1.47 2.00 1.89

Lithium tetrakis(4-(((1S,2S,5S)-6,6-dimethylbicyclo[3.1.1]heptan-2-yl)methyl)-2,3,5,6-tetrafluorophenyl)borate [Li]

_[3]

1_{H NMR (500 MHz, (CD}

3)2CO):

EtOAc

-40 -30 -20 -10 40 30 20 10 0 ppm -1 6.27 11_B{1_{H} NMR (160 MHz, (CD} 3)2CO)

  210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm 22.53 23.28 27.01 28.51 30.30 34.26 39.44 42.19 42.27 45.98 114.53 114.68 114.83 143.63 144.14 145.55 146.05 148.06 148.49 149.91 150.44 13_C{1_{H} NMR (126 MHz, (CD} 3)2CO):

-105 -110 -115 -120 -125 -130 -135 -140 -145 -150 -155 -160 -165 -170 -175 ppm -150.53 -150.51 -150.46 -150.42 -150.40 -133.39 19_F{1_{H} NMR (471 MHz, (CD} 3)2CO):

  10.0 9.0 8.0 7.0 6.0 5.0 4.0 3.0 2.0 1.0 0.0 ppm 0.67 0.83 0.97 1.13 1.30 1.40 1.56 1.64 1.74 1.87 1.99 2.09 2.27 2.40 2.58 3.20 3.34 1.13 6.76 3.92 1.26 1.05 2.19 2.05 1.18 1.22 1.00

Lithium tetrakis(4-(1-((1S,2S,5S)-6,6-dimethylbicyclo[3.1.1]heptan-2-yl)ethyl)-2,3,5,6-tetrafluorophenyl)borate [Li]

_[4]

1_{H NMR (500 MHz, C} 6D6):

-10 10 0 ppm -0. 00 7_{Li NMR (194 MHz, C} 6D6)

  -40 -30 -20 -10 40 30 20 10 0 ppm -1 5.81 11_B{1_{H} NMR (160 MHz, C} 6D6):

210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm 18.04 22.23 23.03 27.00 28.32 34.22 37.21 38.61 41.51 45.18 45.51 119.91 120.05 120.19 143.80 145.72 148.44 150.33 13_C{1_{H} NMR (126 MHz, C} 6D6):

  -105 -110 -115 -120 -125 -130 -135 -140 -145 -150 -155 -160 -165 -170 -175 ppm -150.47 -143.67 -138.24 -131.69 19_{F NMR (471 MHz, C} 6D6):

  10.0 9.0 8.0 7.0 6.0 5.0 4.0 3.0 2.0 1.0 0.0 ppm 0.71 0.84 1.03 1.16 1.22 1.37 1.45 1.58 1.64 1.75 1.88 2.01 2.12 2.28 2.46 2.64 3.26 3.41 1.12 6.58 3.44 1.32 0.97 2.82 2.19 1.14 1.18 1.00

Cesium tetrakis(4-(1-((1S,2S,5S)-6,6-dimethylbicyclo[3.1.1]heptan-2-yl)ethyl)-2,3,5,6-tetrafluorophenyl)borate [Cs]

_[4]

  -40 -30 -20 -10 40 30 20 10 0 ppm -1 5.76 11_B{1_{H} NMR (160 MHz, C} 6D6):

210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm 18.18 22.25 23.05 26.98 28.34 34.28 37.25 38.62 41.46 45.26 45.58 13_C{1_{H} NMR (126 MHz, C} 6D6):

  -105 -110 -115 -120 -125 -130 -135 -140 -145 -150 -155 -160 -165 -170 -175 ppm -150.25 -142.19 -132.30 19_{F NMR (471 MHz, C} 6D6):

  10.0 9.0 8.0 7.0 6.0 5.0 4.0 3.0 2.0 1.0 0.0 ppm 0.62 0.64 1.05 1.09 1.38 1.51 1.56 1.67 1.73 1.84 2.08 2.15 2.18 2.28 2.59 1.00 3.23 3.10 1.16 2.13 3.20 1.03 1.00 2.05

Sodium tetrakis(4-(((1S,2S,5S)-6,6-dimethylbicyclo[3.1.1]heptan-2-yl)methyl)-2,3,5,6-tetrafluorophenyl)borate [Na]

_[3]

1_{H NMR (500 MHz, C} 6D6):

  -40 -30 -20 -10 40 30 20 10 0 ppm -1 5.51 11_B{1_{H} NMR (160 MHz, C} 6D6):

210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm 21.83 23.10 26.67 28.23 30.22 33.95 38.85 41.49 41.64 45.99 13_C{1_{H} NMR (126 MHz, C} 6D6):

  -105 -110 -115 -120 -125 -130 -135 -140 -145 -150 -155 -160 -165 -170 -175 ppm

-147.74

-134.69

19_F{1_{H} NMR (471 MHz, C} 6D6):

  10.0 9.0 8.0 7.0 6.0 5.0 4.0 3.0 2.0 1.0 0.0 ppm 0.72 0.83 1.09 1.15 1.31 1.44 1.55 1.63 1.75 1.88 2.00 2.14 2.27 2.42 2.56 3.23 3.35 1.08 6.04 4.08 1.09 0.77 2.37 1.83 1.02 1.09 1.00

Sodium tetrakis(4-(1-((1S,2S,5S)-6,6-dimethylbicyclo[3.1.1]heptan-2-yl)ethyl)-2,3,5,6-tetrafluorophenyl)borate [Na]

_[4]

1_{H NMR (500 MHz, C} 6D6):

  -40 -30 -20 -10 40 30 20 10 0 ppm -1 5.85 11_B{1_{H} NMR (160 MHz, C} 6D6):

210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm 18.02 22.21 23.03 26.99 28.32 34.23 37.22 38.61 41.49 45.20 45.50 120.20 120.34 120.47 143.86 145.83 148.37 150.26 13_C{1_{H} NMR (126 MHz, C} 6D6):

  -105 -110 -115 -120 -125 -130 -135 -140 -145 -150 -155 -160 -165 -170 -175 ppm -151.53 -143.56 -136.56 -129.01 19_{F NMR (471 MHz, C} 6D6):

  10.0 9.0 8.0 7.0 6.0 5.0 4.0 3.0 2.0 1.0 0.0 ppm 0.70 0.80 1.02 1.12 1.22 1.40 1.54 1.62 1.74 1.97 2.11 2.25 2.41 2.55 1.00 6.17 3.35 1.12 2.97 4.27 1.05 1.07

Sodium tetrakis(4-(1-((1S,2S,5S)-6,6-dimethylbicyclo[3.1.1]heptan-2-yl)ethyl-1,2-d

)-2,3,5,6-tetrafluorophenyl)borate [Na]

[4-d

]

1_{H NMR (500 MHz, C6D6):}

  -40 -30 -20 -10 40 30 20 10 0 ppm -1 5.80 11_B{1_{H} NMR (160 MHz, C} 6D6):

210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm 17.62 22.16 23.00 27.00 28.29 34.20 36.78 38.59 41.49 45.15 45.35 119.93 120.07 120.21 13_C{1_{H} NMR (126 MHz, C} 6D6): acetone

  -105 -110 -115 -120 -125 -130 -135 -140 -145 -150 -155 -160 -165 -170 -175 ppm -150.82 -143.50 -139.05 -130.70 19_{F NMR (471 MHz, C} 6D6):

  10.0 9.0 8.0 7.0 6.0 5.0 4.0 3.0 2.0 1.0 0.0 ppm 0.80 0.82 1.11 1.18 1.51 1.62 1.76 1.91 2.00 2.22 2.34 2.60 2.71 7.58 7.70 7.82 7.84 7.85 8.18 8.29 0.99 2.91 3.23 1.13 4.23 1.10 2.11 2.00 1.40 1.39 0.66

Triphenylmethylium

tetrakis(4-(((1S,2S,5S)-6,6-dimethylbicyclo[3.1.1]heptan-2-yl)methyl)-2,3,5,6-tetrafluorophenyl)borate

[Tr]

_[3]

  -40 -30 -20 -10 40 30 20 10 0 ppm -1 6.42 11_B{1_{H} NMR (161 MHz, CD} 2Cl2):

210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm 22.26 23.14 26.84 28.34 30.16 34.10 39.13 41.77 41.89 45.74 114.46 131.03 140.32 143.06 143.98 13_C{1_{H} NMR (176 MHz, CD} 2Cl2):

  -105 -110 -115 -120 -125 -130 -135 -140 -145 -150 -155 -160 -165 -170 -175 ppm -149.80 -149.77 -149.76 -134.08 19_F{1_{H} NMR (471 MHz, CD} 2Cl2):

  ppm 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0 9.5 ppm 240 220 200 180 160 140 120 100 80 60 40 20 0 1_H/13_{C HMBC NMR (500/175 MHz, CD} 2Cl2) [Tr]+

  10.0 9.0 8.0 7.0 6.0 5.0 4.0 3.0 2.0 1.0 0.0 ppm 0.76 0.85 0.96 1.13 1.18 1.32 1.43 1.58 1.72 1.81 1.95 2.12 2.19 2.32 2.46 3.09 3.29 7.67 7.67 7.69 7.69 7.87 7.88 7.89 7.91 8.28 1.01 5.61 3.85 0.87 1.07 2.18 1.82 1.00 1.18 1.00 1.37 1.37 0.67

Triphenylmethylium

tetrakis(4-(1-((1S,2S,5S)-6,6-dimethylbicyclo[3.1.1]heptan-2-yl)ethyl)-2,3,5,6-tetrafluorophenyl)borate

[Tr]

_[4]

-40 -30 -20 -10 40 30 20 10 0 ppm -1 6.50 11_B{1_{H} NMR (161 MHz, CD} 2Cl2):

  210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm 18.04 22.23 22.91 27.10 28.31 34.32 36.84 38.68 41.61 45.05 45.44 131.03 140.28 143.05 144.01 211.09 13_C{1_{H} NMR (176 MHz, CD} 2Cl2):

-105 -110 -115 -120 -125 -130 -135 -140 -145 -150 -155 -160 -165 -170 -175 ppm -151.85 -145.73 -134.14 19_{F NMR (471 MHz, CD} 2Cl2):

  10.0 9.0 8.0 7.0 6.0 5.0 4.0 3.0 2.0 1.0 0.0 ppm 0.74 0.80 0.88 0.89 0.90 1.02 1.19 1.57 1.67 1.78 1.91 1.93 2.08 2.17 2.26 2.29 2.40 5.55 7.63 7.64 7.65 7.65 7.83 7.84 7.85 8.24 0.69 3.97 1.85 0.62 0.75 1.55 1.37 0.77 0.83 1.00 1.00 0.50

Triphenylmethylium

tetrakis(4-(1-((1S,2S,5S)-6,6-dimethylbicyclo[3.1.1]heptan-2-yl)ethyl-1,2-d

)-2,3,5,6-tetrafluorophenyl)-borate [Tr]

_[4-d

_]

10.0 9.0 8.0 7.0 6.0 5.0 4.0 3.0 2.0 1.0 0.0 ppm 2_{H NMR (107 MHz, CD}

  -40 -30 -20 -10 40 30 20 10 0 ppm -1 6.50 11_B{1_{H} NMR (161 MHz, CD} 2Cl2):

210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm 17.68 17.68 17.79 22.21 22.92 27.12 28.33 34.34 36.13 36.70 38.70 41.65 45.08 45.35 118.91 119.00 119.10 131.04 140.31 143.05 144.02 211.12 13_C{1_{H} NMR (176 MHz, CD} 2Cl2):

  -105 -110 -115 -120 -125 -130 -135 -140 -145 -150 -155 -160 -165 -170 -175 ppm -151.33 -145.56 -134.13 19_{F NMR (471 MHz, CD} 2Cl2):

  10.0 9.0 8.0 7.0 6.0 5.0 4.0 3.0 2.0 1.0 0.0 ppm 0.76 0.78 1.03 1.22 1.39 1.56 1.68 1.78 1.92 2.09 2.15 2.27 2.28 2.41 2.70 3.08 3.18 7.54 7.62 7.66 7.68 7.79 7.81 7.82 8.16 8.18 8.19 1.84 11.13 7.01 1.71 2.03 4.24 3.67 1.96 2.63 1.45 1.78 2.96 0.99 1.96 0.97

Diphenyl(4-tolyl)methylium

tetrakis(4-(1-((1S,2S,5S)-6,6-dimethylbicyclo[3.1.1]heptan-2-yl)ethyl)-2,3,5,6-tetrafluorophenyl)-borate [

_Tr]

_[4]

  -40 -30 -20 -10 40 30 20 10 0 ppm -1 6.48 11_B{1_{H} NMR (161 MHz, CD} 2Cl2):

210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm 18.08 22.28 22.95 23.68 27.14 28.36 34.37 36.88 38.72 41.67 45.12 45.51 118.89 119.03 119.17 130.75 132.50 138.17 140.07 142.02 142.68 143.75 160.76 208.39 13_C{1_{H} NMR (176 MHz, CD} 2Cl2):

  -105 -110 -115 -120 -125 -130 -135 -140 -145 -150 -155 -160 -165 -170 -175 ppm -151.49 -145.07 -134.05 19_{F NMR (471 MHz, CD} 2Cl2):

  10.0 9.0 8.0 7.0 6.0 5.0 4.0 3.0 2.0 1.0 0.0 ppm 0.17 0.93 1.27 1.29 1.31 3.05 3.06 3.21 3.22 3.72 3.74 3.75 3.77 5.94 9.37 3.12 0.97 0.99 2.00

tert

-Butyl((1-ethoxyvinyl)oxy)dimethylsilane (18)

  10.0 9.0 8.0 7.0 6.0 5.0 4.0 3.0 2.0 1.0 0.0 ppm -0.18 0.02 0.85 1.25 2.54 2.72 4.13 5.15 7.22 7.26 7.29 7.37 3.00 2.99 9.23 3.15 1.03 1.03 2.02 1.00 0.83 4.02

Ethyl 3-((tert-butyldimethylsilyl)oxy)-3-phenylpropanoate (20)

210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 ppm -5 .16 -4 .55 14 .33 18 .19 25 .80 46 .64 60 .61 72 .38 125.99 127.61 128.40 144.26 171.37 13_C{1_{H} NMR (101 MHz, CDCl} 3):

  -90 -80 -70 -60 -50 -40 -30 -20 -10 100 90 80 70 60 50 40 30 20 10 0 ppm 19.87 29_{Si DEPT NMR (99 MHz, CDCl} 3):

Ethyl 3-hydroxy-3-phenylpropanoate

1_{H NMR (500 MHz, CDCl} 3):

EtO

  210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm 14 .34 18 .20 25 .82 46 .65 60 .59 72 .40 126.01 127.62 128.41 144.29 171.34 13_C{1_{H} NMR (126 MHz, CDCl} 3):

  10.0 9.0 8.0 7.0 6.0 5.0 4.0 3.0 2.0 1.0 0.0 ppm 0.18 1.66 1.73 3.33 9.00 2.89 2.90 2.87

tert

-Butyl((1-ethoxyvinyl)oxy)dimethylsilan (21)