[(E)-hex-1-enyl]boronic acid

Conditions: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To anhydrous THF (30 ml) containing compound 64 (0.64 g, 2.84 mmol), were added 1.5 eq of (E)-hexene-1-ylboronic acid (0.55 g). The resulting mixture was stirred for 2 hours under N2. Successively were added 2 eq of K3PO4 (1.2 g), 2 mol % of Pd(OAc)2 (13 mg) and 4 mol % of S-Phos (47 mg). After the addition, the resulting solution was warmed at 65° C. for 18 hours under N2. After cooling to room temperature, the mixture was diluted with ethyl acetate, washed with a saturated NaHCO3 solution, dried (Na2SO4), filtered and concentrated. The resulting residue was purified by flash chromatography (diethyl ether/PE 1/1) to afford 3-(4-hex-1-enyl-isoxazol-3-yl)-pyridine (compound 67A) as an oil (0.47 g, 69%). 1H-NMR (400 MHz, CDCl3): δ 8.9 (d, J=2 Hz, 1H), 8.72 (dd, J=5 Hz, 2 Hz, 1H), 8.49 (s, 1H), 8.0 (dt, J=8 Hz, 2 Hz, 1H), 7.45-7.41 (m, 1H), 6.11-5.99 (m, 2H), 2.22-2.14 (m, 2H), 1.46-1.29 (m, 4H), 0.91 (t, J=7 Hz, 3H). After the addition After cooling to room temperature washed with a saturated NaHCO3 solution dried (Na2SO4) filtered concentrated The resulting residue was purified by flash chromatography (diethyl ether/PE 1/1)

Conditions: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To anhydrous THF (30 ml) containing compound 64 (0.64 g, 2.84 mmol), were added 1.5 eq of (E)-hexene-1-ylboronic acid (0.55 g). The resulting mixture was stirred for 2 hours under N2. Successively were added 2 eq of K3PO4 (1.2 g), 2 mol % of Pd(OAc)2 (13 mg) and 4 mol % of S-Phos (47 mg). After the addition, the resulting solution was warmed at 65° C. for 18 hours under N2. After cooling to room temperature, the mixture was diluted with ethyl acetate, washed with a saturated NaHCO3 solution, dried (Na2SO4), filtered and concentrated. The resulting residue was purified by flash chromatography (diethyl ether/PE 1/1) to afford 3-(4-hex-1-enyl-isoxazol-3-yl)-pyridine (compound 67A) as an oil (0.47 g, 69%). 1H-NMR (400 MHz, CDCl3): δ 8.9 (d, J=2 Hz, 1H), 8.72 (dd, J=5 Hz, 2 Hz, 1H), 8.49 (s, 1H), 8.0 (dt, J=8 Hz, 2 Hz, 1H), 7.45-7.41 (m, 1H), 6.11-5.99 (m, 2H), 2.22-2.14 (m, 2H), 1.46-1.29 (m, 4H), 0.91 (t, J=7 Hz, 3H). After the addition After cooling to room temperature washed with a saturated NaHCO3 solution dried (Na2SO4) filtered concentrated The resulting residue was purified by flash chromatography (diethyl ether/PE 1/1)

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To toluene (20 ml) containing 36A (0.67 g, 1.84 mmol) (see Scheme 7), was added 1.5 eq of (E)-hexene-1-ylboronic acid (0.35 g). The resulting mixture was stirred for 2 hours under N2. Successively were added 2 eq of K3PO4 (0.78 g), 4 mol % of Pd(OAc)2 (16.5 mg) and 8 mol % of S-Phos (60.4 mg). After the addition, the resulting solution was warmed at 90° C. for 18 hours under N2. After cooling to room temperature, the mixture was diluted with ethyl acetate, washed three times with a saturated NaHCO3 solution, dried (Na2SO4), filtered and concentrated. The resulting residue was purified by flash chromatography (diethyl ether/PE 1/1) to afford 3-(1-phenylsulfonyl-4-hex-1-enyl-1H-pyrazol-3-yl)-pyridine (46A) as an oil (0.38 g, 61%). 1H-NMR (400 MHz, CDCl3): δ 8.8 (d, J=2 Hz, 1H), 8.6 (dd, J=5 Hz, 2 Hz, 1H), 8.15 (s, 1H), 8.10-8.05 (m, 2H), 7.94 (dt, J=8 Hz, 2 Hz, 1H), 7.70-7.64 (m, 1H), 7.56 (bt, J=8 Hz, 2H), 7.37-7.33 (m, 1H), 6.19-6.02 (m, 1H), 2.2-2.13 (m, 2H), 1.45-1.29 (m, 4H), 0.90 (t, J=7 Hz, 3H). After the addition After cooling to room temperature washed three times with a saturated NaHCO3 solution dried (Na2SO4) filtered concentrated The resulting residue was purified by flash chromatography (diethyl ether/PE 1/1)

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To toluene (20 ml) containing 36A (0.67 g, 1.84 mmol) (see Scheme 7), was added 1.5 eq of (E)-hexene-1-ylboronic acid (0.35 g). The resulting mixture was stirred for 2 hours under N2. Successively were added 2 eq of K3PO4 (0.78 g), 4 mol % of Pd(OAc)2 (16.5 mg) and 8 mol % of S-Phos (60.4 mg). After the addition, the resulting solution was warmed at 90° C. for 18 hours under N2. After cooling to room temperature, the mixture was diluted with ethyl acetate, washed three times with a saturated NaHCO3 solution, dried (Na2SO4), filtered and concentrated. The resulting residue was purified by flash chromatography (diethyl ether/PE 1/1) to afford 3-(1-phenylsulfonyl-4-hex-1-enyl-1H-pyrazol-3-yl)-pyridine (46A) as an oil (0.38 g, 61%). 1H-NMR (400 MHz, CDCl3): δ 8.8 (d, J=2 Hz, 1H), 8.6 (dd, J=5 Hz, 2 Hz, 1H), 8.15 (s, 1H), 8.10-8.05 (m, 2H), 7.94 (dt, J=8 Hz, 2 Hz, 1H), 7.70-7.64 (m, 1H), 7.56 (bt, J=8 Hz, 2H), 7.37-7.33 (m, 1H), 6.19-6.02 (m, 1H), 2.2-2.13 (m, 2H), 1.45-1.29 (m, 4H), 0.90 (t, J=7 Hz, 3H). After the addition After cooling to room temperature washed three times with a saturated NaHCO3 solution dried (Na2SO4) filtered concentrated The resulting residue was purified by flash chromatography (diethyl ether/PE 1/1)

Conditions: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 5-(2-benzyloxy-4-iodophenyl)-1,1-dioxo-1,2,5-thiadiazolidin-3-one (200 mg, 0.45 mmol), trans-1-hexen-1-ylboronic acid (77 mg, 0.676 mmol), resin-bound PPh3Pd (692 mg, loading 0.13 mmol/g) and aqueous Na2CO3 (0.9 mL of a 2M solution) in DME (3 mL) is placed in a microwave vial and heated at 110° C. for 30 min. The mixture is filtered, diluted with EtOAc and washed with 1N HCl. The organic phase is dried over magnesium sulfate and the solvent removed under reduced pressure. The residue is purified by preparative HPLC to give the title compound. The mixture is filtered diluted with EtOAc washed with 1N HCl The organic phase is dried over magnesium sulfate the solvent removed under reduced pressure The residue is purified by preparative HPLC

Conditions: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To anhydrous THF (30 ml) containing compound 64 (0.64 g, 2.84 mmol), were added 1.5 eq of (E)-hexene-1-ylboronic acid (0.55 g). The resulting mixture was stirred for 2 hours under N2. Successively were added 2 eq of K3PO4 (1.2 g), 2 mol % of Pd(OAc)2 (13 mg) and 4 mol % of S-Phos (47 mg). After the addition, the resulting solution was warmed at 65° C. for 18 hours under N2. After cooling to room temperature, the mixture was diluted with ethyl acetate, washed with a saturated NaHCO3 solution, dried (Na2SO4), filtered and concentrated. The resulting residue was purified by flash chromatography (diethyl ether/PE 1/1) to afford 3-(4-hex-1-enyl-isoxazol-3-yl)-pyridine (compound 67A) as an oil (0.47 g, 69%). 1H-NMR (400 MHz, CDCl3): δ 8.9 (d, J=2 Hz, 1H), 8.72 (dd, J=5 Hz, 2 Hz, 1H), 8.49 (s, 1H), 8.0 (dt, J=8 Hz, 2 Hz, 1H), 7.45-7.41 (m, 1H), 6.11-5.99 (m, 2H), 2.22-2.14 (m, 2H), 1.46-1.29 (m, 4H), 0.91 (t, J=7 Hz, 3H). After the addition After cooling to room temperature washed with a saturated NaHCO3 solution dried (Na2SO4) filtered concentrated The resulting residue was purified by flash chromatography (diethyl ether/PE 1/1)

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To toluene (20 ml) containing 36A (0.67 g, 1.84 mmol) (see Scheme 7), was added 1.5 eq of (E)-hexene-1-ylboronic acid (0.35 g). The resulting mixture was stirred for 2 hours under N2. Successively were added 2 eq of K3PO4 (0.78 g), 4 mol % of Pd(OAc)2 (16.5 mg) and 8 mol % of S-Phos (60.4 mg). After the addition, the resulting solution was warmed at 90° C. for 18 hours under N2. After cooling to room temperature, the mixture was diluted with ethyl acetate, washed three times with a saturated NaHCO3 solution, dried (Na2SO4), filtered and concentrated. The resulting residue was purified by flash chromatography (diethyl ether/PE 1/1) to afford 3-(1-phenylsulfonyl-4-hex-1-enyl-1H-pyrazol-3-yl)-pyridine (46A) as an oil (0.38 g, 61%). 1H-NMR (400 MHz, CDCl3): δ 8.8 (d, J=2 Hz, 1H), 8.6 (dd, J=5 Hz, 2 Hz, 1H), 8.15 (s, 1H), 8.10-8.05 (m, 2H), 7.94 (dt, J=8 Hz, 2 Hz, 1H), 7.70-7.64 (m, 1H), 7.56 (bt, J=8 Hz, 2H), 7.37-7.33 (m, 1H), 6.19-6.02 (m, 1H), 2.2-2.13 (m, 2H), 1.45-1.29 (m, 4H), 0.90 (t, J=7 Hz, 3H). After the addition After cooling to room temperature washed three times with a saturated NaHCO3 solution dried (Na2SO4) filtered concentrated The resulting residue was purified by flash chromatography (diethyl ether/PE 1/1)

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To toluene (20 ml) containing 36A (0.67 g, 1.84 mmol) (see Scheme 7), was added 1.5 eq of (E)-hexene-1-ylboronic acid (0.35 g). The resulting mixture was stirred for 2 hours under N2. Successively were added 2 eq of K3PO4 (0.78 g), 4 mol % of Pd(OAc)2 (16.5 mg) and 8 mol % of S-Phos (60.4 mg). After the addition, the resulting solution was warmed at 90° C. for 18 hours under N2. After cooling to room temperature, the mixture was diluted with ethyl acetate, washed three times with a saturated NaHCO3 solution, dried (Na2SO4), filtered and concentrated. The resulting residue was purified by flash chromatography (diethyl ether/PE 1/1) to afford 3-(1-phenylsulfonyl-4-hex-1-enyl-1H-pyrazol-3-yl)-pyridine (46A) as an oil (0.38 g, 61%). 1H-NMR (400 MHz, CDCl3): δ 8.8 (d, J=2 Hz, 1H), 8.6 (dd, J=5 Hz, 2 Hz, 1H), 8.15 (s, 1H), 8.10-8.05 (m, 2H), 7.94 (dt, J=8 Hz, 2 Hz, 1H), 7.70-7.64 (m, 1H), 7.56 (bt, J=8 Hz, 2H), 7.37-7.33 (m, 1H), 6.19-6.02 (m, 1H), 2.2-2.13 (m, 2H), 1.45-1.29 (m, 4H), 0.90 (t, J=7 Hz, 3H). After the addition After cooling to room temperature washed three times with a saturated NaHCO3 solution dried (Na2SO4) filtered concentrated The resulting residue was purified by flash chromatography (diethyl ether/PE 1/1)

Conditions: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To anhydrous THF (30 ml) containing compound 64 (0.64 g, 2.84 mmol), were added 1.5 eq of (E)-hexene-1-ylboronic acid (0.55 g). The resulting mixture was stirred for 2 hours under N2. Successively were added 2 eq of K3PO4 (1.2 g), 2 mol % of Pd(OAc)2 (13 mg) and 4 mol % of S-Phos (47 mg). After the addition, the resulting solution was warmed at 65° C. for 18 hours under N2. After cooling to room temperature, the mixture was diluted with ethyl acetate, washed with a saturated NaHCO3 solution, dried (Na2SO4), filtered and concentrated. The resulting residue was purified by flash chromatography (diethyl ether/PE 1/1) to afford 3-(4-hex-1-enyl-isoxazol-3-yl)-pyridine (compound 67A) as an oil (0.47 g, 69%). 1H-NMR (400 MHz, CDCl3): δ 8.9 (d, J=2 Hz, 1H), 8.72 (dd, J=5 Hz, 2 Hz, 1H), 8.49 (s, 1H), 8.0 (dt, J=8 Hz, 2 Hz, 1H), 7.45-7.41 (m, 1H), 6.11-5.99 (m, 2H), 2.22-2.14 (m, 2H), 1.46-1.29 (m, 4H), 0.91 (t, J=7 Hz, 3H). After the addition After cooling to room temperature washed with a saturated NaHCO3 solution dried (Na2SO4) filtered concentrated The resulting residue was purified by flash chromatography (diethyl ether/PE 1/1)

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To toluene (20 ml) containing 36A (0.67 g, 1.84 mmol) (see Scheme 7), was added 1.5 eq of (E)-hexene-1-ylboronic acid (0.35 g). The resulting mixture was stirred for 2 hours under N2. Successively were added 2 eq of K3PO4 (0.78 g), 4 mol % of Pd(OAc)2 (16.5 mg) and 8 mol % of S-Phos (60.4 mg). After the addition, the resulting solution was warmed at 90° C. for 18 hours under N2. After cooling to room temperature, the mixture was diluted with ethyl acetate, washed three times with a saturated NaHCO3 solution, dried (Na2SO4), filtered and concentrated. The resulting residue was purified by flash chromatography (diethyl ether/PE 1/1) to afford 3-(1-phenylsulfonyl-4-hex-1-enyl-1H-pyrazol-3-yl)-pyridine (46A) as an oil (0.38 g, 61%). 1H-NMR (400 MHz, CDCl3): δ 8.8 (d, J=2 Hz, 1H), 8.6 (dd, J=5 Hz, 2 Hz, 1H), 8.15 (s, 1H), 8.10-8.05 (m, 2H), 7.94 (dt, J=8 Hz, 2 Hz, 1H), 7.70-7.64 (m, 1H), 7.56 (bt, J=8 Hz, 2H), 7.37-7.33 (m, 1H), 6.19-6.02 (m, 1H), 2.2-2.13 (m, 2H), 1.45-1.29 (m, 4H), 0.90 (t, J=7 Hz, 3H). After the addition After cooling to room temperature washed three times with a saturated NaHCO3 solution dried (Na2SO4) filtered concentrated The resulting residue was purified by flash chromatography (diethyl ether/PE 1/1)

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of glyoxylic acid monohydrate (80 mg, 0.87 mmol) in ethanol (6 mL) was added morpholine (76 mg, 0.87 mmol) in one portion. After 5 min (E)-1-hexenyl boronic acid (121 mg, 0.82 mmol) was added. The reaction mixture was heated at 50° C. for 36 hours, after which time precipitate was isolated by filtration, washed with cold ethanol (10 mL) and dried under vacuum to give (E)-2-morpholino-3-octenoic acid (177 mg,78% yield). 1H-NMR (360 MHz, d6-DMSO) δ 5.65 (dt, J=16.1 Hz, 7.0 Hz, 1H), 5.28 (dd, J=16.1 Hz, 9.1 Hz, 1H), 4.81 (d, J=9.1 Hz, 1H), 2.50 (m, 2H), 1.1 (m, 4H), 0.7 (t, J=7.1 Hz, 3H). 13C-NMR (90 MHz, d6-DMSO) δ 171.1, 136.7, 127.4, 68.8, 62.5, 56.7, 31.7, 30.2, 22.1, 13.9. HRMS-CI (M++1) Calcd for C12H21NO3: 228.1521, Found: 228.1513. after which time precipitate was isolated by filtration washed with cold ethanol (10 mL) dried under vacuum

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In a dried and purged vessel were added N-[(2-bromo-1,3-thiazol-4-yl)methoxy]-1-(1-methyl-1H-tetrazol-5-yl)-1-phenylmethanimine (0.2 g, 0.527 mmol, 1 eq.), (1E)-hex-1-en-1-ylboronic acid (0.074 g, 0.58 mmol, 1.1 eq.), Na2CO3 (0.117 g, 1.107 mmol, 2.1 eq.) and Tetrakis(triphenylphosphine)palladium (0.030 g, 0.026 mmol, 0.05 eq.). A mixture of solvent was added toluene/ethanol/water (4/1/1) was added and the vessel purged with argon and sealed. The reaction was heated to 90° C. for 6 hrs. After cooling, 10 ml of EtOAc were added and the solids were filtered through a “Celite” plug and washed with EtOAc. The organics were separated, dried over MgSO4 and concentrated. The residue was purified by chromatography on silica gel to give N-({2-[(1E)-hex-1-en-1-yl]-1,3-thiazol-4-yl}methoxy)-1-(1-methyl-1H-tetrazol-5-yl)-1-phenylmethanimine (0.170 g, 80% yield) as a colorless gum. In a dried purged vessel A mixture of solvent was added the vessel purged with argon sealed After cooling 10 ml of EtOAc were added the solids were filtered through a “Celite” plug washed with EtOAc The organics were separated dried over MgSO4 concentrated The residue was purified by chromatography on silica gel