Correction: Effect of heterocycle content on metal binding isostere coordination

Correction for ‘Effect of heterocycle content on metal binding isostere coordination’ by Benjamin L. Dick et al., Chem. Sci., 2020, 11, 6907–6914, DOI: 10.1039/D0SC02717K.


O-methyl indazole-3-hydroxamic acid (1a). In a round bottom flask indazole-3-carboxylic acid
(300 mg, 1 equiv, 1.9 mmol) was dissolved in 10 mL of DMF. 1,1'-Carbonyldiimidazole (CDI) (300 mg, 1 equiv, 1.9 mmol) was added to the solution and stirred for 1 h under nitrogen at room temperature. O-methylhydroxylamine hydrochloride (309 mg, 2 equiv, 3.7 mmol) was added to the reaction and stirred overnight under nitrogen at room temperature. The reaction was dried down via rotary evaporation to a yellow-brown oil and loaded onto silica. The product was

O-methyl benzimidazole-2-hydroxamic acid (2a). In a round bottom flask benzimidazole-2-
carboxylic acid (300 mg, 1 equiv, 1.9 mmol) was dissolved in 10 mL of DMF. 1,1'-Carbonyldiimidazole (CDI) (300 mg, 1 equiv, 1.9 mmol) was added to the solution and stirred for 1 h under nitrogen at room temperature. O-methylhydroxylamine hydrochloride (310 mg, 2 equiv, 3.7 mmol) was added to the reaction mixture and stirred overnight under nitrogen at room temperature. The reaction mixture was then dried down via rotary evaporation giving a brown oil that was purified via column chromatography using a 0-60 % Hexanes:EtOAc gradient. The

O-methyl 1,2-benzisothiazole-3-hydroxamic acid (3a).
To a solution of 1,2-benzisothiazole-3carboxylic acid (300 mg, 1 equiv, 1.7 mmol) in 25 mL of CH2Cl2, oxalyl chloride (637 mg, 0.440 mL, 3 equiv, 5.0 mmol) was slowly added along with 5 drops of DMF. The solution was stirred for 3 h at room temperature under nitrogen. The reaction mixture was then evaporated to provide the crude acid chloride which was moved forward to the next step. The dried solids were dissolved S11 in 25 mL of CH2Cl2 and O-methylhydroxylamine hydrochloride (168 mg, 1.2 equiv, 2.0 mmol) and triethylamine (678 mg, 0.933 mL, 4 equiv, 6.7 mmol) were added. The mixture was stirred overnight at room temperature under nitrogen. The reaction mixture was washed with a saturated brine solution and the organic layer was dried over MgSO4. The organic layer was then dried down via rotary evaporation and loaded onto silica. The product was purified via column chromatography using a 0-40% Hexanes:EtOAc gradient. The fractions containing product were

O-methyl benzothiazole-2-hydroxamic acid (4a).
To a solution of benzothiazole-2-carboxylic acid (500 mg, 1 equiv, 2.79 mmol) in 50 mL of CH2Cl2, oxalyl chloride (1.06 g, 0.733 mL, 3 equiv, 8.37 mmol) was slowly added along with 5 drops of DMF. The reaction as stirred for 3 h at room temperature under nitrogen. The reaction mixture was then dried down to a solid via rotary evaporation to provide the crude acid chloride which was moved forward onto the next step. To a solution of the crude acid chloride dissolved in 50 mL of CH2Cl2, O-methylhydroxylamine hydrochloride (280 mg, 1.2 equiv, 3.4 mmol) and triethylamine (678 mg, 0.93 mL, 2.4 equiv, 6.7 mmol) were added. The reaction was stirred at room temperature for 2 h. The reaction solution S12 was then washed with a saturated brine solution, dried over MgSO4, and dried down to a brown solid and loaded onto silica. The product was purified via column chromatography using a gradient O-methyl 1,2-benzisothiazole-3-hydroxamic acid (5a). In a round bottom flask 1,2benzisoxazole-3-carboxylic acid (300 mg, 1 equiv, 1.84 mmol) was dissolved in CH2Cl2 (10 mL).
Thionyl chloride (3.3 g, 2.0 mL, 15 equiv, 28 mmol) was added slowly along with a few drops of DMF. The reaction mixture was then stirred at room temperature under a nitrogen atmosphere for 3 to 4 hr. The reaction mixture was dried down to a tan residue and redissolved in CH2Cl2 (10 mL). O-methylhydroxylamine hydrochloride (307 mg, 2 equiv, 3.68 mmol) and triethylamine (744 mg, 1.0 mL, 4 equiv, 7.36 mmol) were added and the reaction was stirred at room temperature overnight under a nitrogen atmosphere. The reaction mixture was dried down via rotary evaporation and loaded onto silica. The product was isolated via column chromatography using a 0-20% Hexanes:EtOAc gradient. Fractions containing product were dried down via rotary evaporation to obtain a white solid. The product was recrystallized in Hexanes:EtOAc resulting S13 in clear block crystals which were collected via filtration. Yield: 80 mg (23%

Indazole-3-hydroxamic acid (1b).
To a solution of indazole-3-carboxylic acid (500 mg, 1 equiv, 3.1 mmol) dissolved in 10 mL of DMF, CDI (500 mg, 1 equiv, 3.1 mmol) was added and the solution was stirred for 1 h under nitrogen at room temperature. Hydroxylamine hydrochloride (429 mg, 2 equiv, 6.2 mmol) was added to the reaction and the mixture was stirred overnight under nitrogen at room temperature. The reaction mixture was dried via rotary evaporation and loaded onto silica. The product was purified via column chromatography using a 0-100% Hexanes:EtOAc gradient. The fractions containing product were dried down via rotary evaporation and the product was isolated by dissolving the solid in a minimal amount of MeOH and titrating with chloroform resulting in the product precipitating out as a white solid which was collected via vacuum filtration and dried. Yield: 110 mg (20%). 1 H NMR (300 MHz, DMSO-d6): δ 13.52 (s, 1H), 11.14 (s, 1H), Benzimidazole-2-hydroxamic acid (2b). To a solution of benzimidazole-2-carboxylic acid (500 mg, 1 equiv, 3.1 mmol) dissolved in 10 mL of DMF, CDI (500 mg, 1 equiv, 3.08 mmol) was added to the solution and stirred for 1 h under nitrogen at room temperature. Hydroxylamine hydrochloride (429 mg, 2.0 equiv, 6.17 mmol) was added to the reaction mixture and stirred overnight under nitrogen at room temperature. The reaction solution was dried down to a brown residue and loaded onto silica. The product was purified via column chromatography using a 0-
N'-hydroxy 1,2-benzisothiazole-3-amidine. In a round bottom flask 1,2-benzisothiazole-3carbonitrile (500 mg, 1 equiv, 3.12 mmol) was dissolved in 50 mL of EtOH. Hydroxylamine hydrochloride (434 mg, 2 equiv, 6.24 mmol) and potassium carbonate (431 mg, 1 equiv, 3.12 mmol) were added to the solution and stirred while the mixture was heated to reflux (90 ºC) overnight. The reaction mixture was dried down via rotary evaporation and then the resulting solid was dissolved in water and EtOAc. The aqueous layer was adjusted to neutral pH and the organic layer was dried with MgSO4. The organic layer was dried down and the product was obtained as a white solid. Yield: 450 mg (75% N'-hydroxy benzothiazole-2-amidine. In a round bottom flask benzothiazole-2-carbonitrile (500 mg, 1 equiv, 3.12 mmol) was dissolved in 50 mL of EtOH. Hydroxylamine hydrochloride (434 S27 mg, 2 equiv, 6.24 mmol) and potassium carbonate (431 mg, 1 equiv, 3.12 mmol) were added to the solution and stirred while the mixture was heated to reflux (90 ºC) overnight. The reaction mixture was dried down via rotary evaporation and then the resulting solid was dissolved in water and EtOAc. The aqueous layer was adjusted to neutral pH and the organic layer was dried with MgSO4. The organic layer was dried down via rotary evaporation and the product was obtained as a white solid. Yield: 580 mg (96%  4, 159.34, 151.2, 145.4, 132.0, 126.0, 122.8, 117.7, 110.5  The asymmetric unit consists of the complex and two and a half molecules of benzene (not shown).
Color scheme: carbon = gray, oxygen = red, nitrogen = blue, boron = pink, and zinc = green. The asymmetric unit consists of two complexes (one not shown). Color scheme: carbon = gray, sulfur = yellow, oxygen = red, nitrogen = blue, boron = pink, and zinc = green.  The asymmetric unit consists of two complexes (one not shown) and three molecules of benzene (not shown). Color scheme: carbon = gray, oxygen = red, nitrogen = blue, boron = pink, and zinc = green.   The asymmetric unit consists of the complex and two molecules of benzene (not shown). Color scheme: carbon = gray, oxygen = red, nitrogen = blue, boron = pink, and zinc = green.  The asymmetric unit consists of two complexes (one not shown) and two molecules of benzene (not shown). Color scheme: carbon = gray, sulfur = yellow, oxygen = red, nitrogen = blue, boron = pink, and zinc = green. Figure S15. Structure of [(Tp Ph,Me )Zn(5b)] rendered as an ORTEP with atoms at 50% thermal probability ellipsoids. Hydrogen atoms and Tp Ph,Me phenyl groups have been removed for clarity.

S37
The asymmetric unit consists of the complex and a molecule of water (not shown). Color scheme: carbon = gray, oxygen = red, nitrogen = blue, boron = pink, and zinc = green.  The asymmetric unit consists of the complex and a molecule of benzene (not shown). Color scheme: carbon = gray, sulfur = yellow, nitrogen = blue, boron = pink, and zinc = green. The asymmetric unit consists of just the complex. Color scheme: carbon = gray, oxygen = red, nitrogen = blue, boron = pink, and zinc = green. The asymmetric unit consists of two complexes (one not shown) and three molecules of MeOH (not shown). Color scheme: carbon = gray, oxygen = red, nitrogen = blue, boron = pink, and zinc = green. The asymmetric unit consists only of the complex. Color scheme: carbon = gray, oxygen = red, nitrogen = blue, boron = pink, and zinc = green. Figure S23. Structure of [(Tp Ph,Me )Zn(3d)] rendered as an ORTEP with atoms at 50% thermal probability ellipsoids. Hydrogen atoms and Tp Ph,Me phenyl groups have been removed for clarity.

S41
The asymmetric unit consists of just the complex. Color scheme: carbon = gray, oxygen = red, sulfur = yellow, nitrogen = blue, boron = pink, and zinc = green. The asymmetric unit consists of the complex and a molecule of benzene (not shown). Color scheme: carbon = gray, oxygen = red, sulfur = yellow, nitrogen = blue, boron = pink, and zinc = green. Figure S25. Structure of [(Tp Ph,Me )Zn(5d)] rendered as an ORTEP with atoms at 50% thermal probability ellipsoids. Hydrogen atoms and Tp Ph,Me phenyl groups have been removed for clarity.