Supporting Information

Self-templated synthesis of an orthoformate inin-cryptand and its bridgehead

inversion by dynamic covalent exchange

Henrik Loumlw Elena Mena-Osteritz and Max von Delius

Institute of Organic Chemistry University of Ulm Albert-Einstein-Allee 11 89081 Ulm (Germany)

Email maxvondeliusuni-ulmde

Contents

1 General Experimental Section 3

2 Synthetic Procedures and Characterization Data 4

21 Synthesis of Orthoester Cryptates 4

Synthesis of o-(Hin)2-111 4

Synthesis of [Li+o-(H)2-111]BArF- 6

Synthesis of o-(H)2-111 6

Synthesis of [Na+o-(H)2-111]BArF- 6

22 Interconversion of orthoformate cryptands 8

3 Experimental Binding Studies 9

4 Crystallographic Data 11

Compound o-(Hin)2-111 11

Compound [Na+o-(H)2-111]BArF- 12

Analysis of intramolecular hydrogen bonds in o-(Hin)2-111 13

Analysis of M+-O distances O-C-O angles and R-C-O-M torsion angles in orthoformate and

orthoacetate cryptands 13

5 References 14

Electronic Supplementary Material (ESI) for ChemCommThis journal is copy The Royal Society of Chemistry 2019

S3

1 General Experimental Section

Reagents and instruments

All commercially available reagents were purchased from Sigma Aldrich Alfa Aesar Acros Organics or

TCI and were used without further purification Molecular sieves and aluminum oxide were dried for 3 days

at 150 degC under reduced pressure (10-2 mbar) before use CDCl3 was dried for at least 3 days over molecular

sieves All solvents were dried over molecular sieves for at least 24 hours All orthoester exchange reactions

(catalyzed by TFA) were carried out under nitrogen NMR spectra were recorded on Bruker Avance 400 or

Bruker Avance 500 (1H 400 or 500 MHz) spectrometers at 298 K and referenced to the residual solvent

peak (1H CDCl3 726 ppm CD3CN 194 ppm CD2Cl2 532 ppm 13C CDCl3 770 ppm CD3CN 132

ppm CD2Cl2 5384 ppm) Coupling constants (J) are denoted in Hz and chemical shifts (δ) in ppm Mass

spectra were obtained on a Bruker SolariX (HRMS-ESI+ Solvent methanol or acetonitrile) instrument

Lithium tetrakis[35-bis(trifluoromethyl)phenyl]borate was synthesized according to literature procedures1

General Procedures

General Procedure A (metal-templated cryptate syntheses)

Drying of starting materials Sodium tetrakis[35-bis(trifluoromethyl)phenyl]borate or Lithium tetrakis[35-

bis(trifluoromethyl)phenyl]borate was dissolved in anhydrous acetonitrile trimethyl orthoformate (1 mL

per gram MBArF) and a catalytic amount of TFA were added The solvent was removed under reduced

pressure and the salt was dried under high vacuum Diethylene glycol was dried and stored over 3 Aring MS

and aluminum oxide

Sodium tetrakis[35-bis(trifluoromethyl)phenyl]borate (60 micromol 10 equiv 54 mg) or Lithium tetrakis[35-

bis(trifluoromethyl)phenyl]borate (60 micromol 10 equiv 52 mg) diethylene glycol (180 micromol 30 equiv

173 microL) and anhydrous trimethyl orthoformate (120 micromol 20 equiv 133 microL) were dissolved in

anhydrous chloroform (6 mL) under inert atmosphere TFA stock solution (12 micromol 001 equiv 10 microL)

was added After equilibration of the reaction mixture 5 Aring MS was added The reaction progress was

monitored by 1H-NMR spectroscopy If needed more TFA stock solution was added Upon completion the

reaction was quenched by addition of triethylamine and the solvent was removed under reduced pressure

The crude product was purified by passing it over a short plug of silica gel The plug was rinsed with

anhydrous chloroform and removal of the solvent under reduced pressure gave the corresponding salts as

colourless solids

General Procedure B (NMR titrations)

Stock solutions of cryptand and NaBArF in CDCl3 were prepared The precise quantity of cryptand or metal

salt was determined with 14-dinitrobenzene as internal standard A cryptand stock solution with precise

concentration was prepared via dilution To the solution of metal salt cryptand stock solution was added to

keep the concentration of cryptand during the titration constant 600 microL of cryptand stock solution were

added to a standard NMR tube varying amounts of metal salt stock solution were added The titration was

monitored by 1H NMR spectroscopy (temperature 298 K) Binding constants were fitted using Bindfit All

raw data calculated fits and related data can be accessed via wwwsupramolecularorg

S4

2 Synthetic Procedures and Characterization Data

21 Synthesis of Orthoester Cryptates

Synthesis of o-(Hin)2-111

Diethylene glycol (36 mmol 30 equiv 345 microL) and trimethyl orthoformate

(24 mmol 20 equiv 265 microL) were dissolved in anhydrous chloroform (60 mL) under

inert atmosphere TFA (24 micromol 001 equiv 186 microL) was added After equilibration

of the reaction mixture 5 Aring MS was added The reaction progress was monitored by 1H-

NMR spectroscopy After 1 day more TFA (24 micromol 001 equiv 186 microL) was added

After 3 days in total the reaction was quenched by addition of triethylamine and the

solvent was removed under reduced pressure The crude product was purified by washing with diethyl ether

to give o-(Hin)2-111 as crystalline solid (206 mg 51)

1H-NMR (500 MHz CD3CN 298 K) δ (ppm) = 603 (s 2H c) 378 ndash 370 (m 12H b) 358 ndash 351 (m

12H a)

13C-NMR (125 MHz CD3CN 298 K) δ (ppm) = 1186 737 646

HRMS (ESI+) mz = 3611471 [M+Na]+ (calcd 3611469 for C14H26NaO9)

mp degradation gt250 degC

1H NMR spectrum (500 MHz CD3CN 298 K)

S5

13C NMR spectrum (125 MHz CD3CN 298 K)

1H NOE NMR spectrum (400 MHz CDCl3 298 K)

S6

Synthesis of [Li+o-(H)2-111]BArF-

The synthesis of [Li+o-(H)2-111]BArF- was reported

previously2 [Li+o-(H)2-111]BArF- was prepared

according to general procedure A The yield was improved

to 55 (40 mg)

Synthesis of o-(H)2-111

The synthesis of Synthesis of o-(H)2-111 was reported previously2

Synthesis of [Na+o-(H)2-111]BArF-

o-(H)2-111 (147 micromol 10 equiv 50 mg) was dissolved in

acetonitrile and NaBArF (147 micromol 10 equiv 131 mg)

was added The mixture was stirred for 5 min removal of the

solvent gave the product [Na+o-(H)2-111]BArF- as

colourless solid (181 mg quant)

1H-NMR (500 MHz CD2Cl2 298 K) δ (ppm) = 774 ndash 770

(m 8H) 758 ndash 755 (m 4H) 554 (s 2H c) 397 ndash 395 (m

12H b) 365 ndash 363 (m 12H a)

13C-NMR (125 MHz CD2Cl2 298 K) δ (ppm) = 1620 1616 1352 1283 1261 1239 1179 1179

1179 1178 1074 704 634

HRMS (ESI+) mz = 3611470 [M+Na]+ (calcd 3611469 for C14H26NaO9)

mp 182 degC

S3

1 General Experimental Section

Reagents and instruments

All commercially available reagents were purchased from Sigma Aldrich Alfa Aesar Acros Organics or

TCI and were used without further purification Molecular sieves and aluminum oxide were dried for 3 days

at 150 degC under reduced pressure (10-2 mbar) before use CDCl3 was dried for at least 3 days over molecular

sieves All solvents were dried over molecular sieves for at least 24 hours All orthoester exchange reactions

(catalyzed by TFA) were carried out under nitrogen NMR spectra were recorded on Bruker Avance 400 or

Bruker Avance 500 (1H 400 or 500 MHz) spectrometers at 298 K and referenced to the residual solvent

peak (1H CDCl3 726 ppm CD3CN 194 ppm CD2Cl2 532 ppm 13C CDCl3 770 ppm CD3CN 132

ppm CD2Cl2 5384 ppm) Coupling constants (J) are denoted in Hz and chemical shifts (δ) in ppm Mass

spectra were obtained on a Bruker SolariX (HRMS-ESI+ Solvent methanol or acetonitrile) instrument

Lithium tetrakis[35-bis(trifluoromethyl)phenyl]borate was synthesized according to literature procedures1

General Procedures

General Procedure A (metal-templated cryptate syntheses)

Drying of starting materials Sodium tetrakis[35-bis(trifluoromethyl)phenyl]borate or Lithium tetrakis[35-

bis(trifluoromethyl)phenyl]borate was dissolved in anhydrous acetonitrile trimethyl orthoformate (1 mL

per gram MBArF) and a catalytic amount of TFA were added The solvent was removed under reduced

pressure and the salt was dried under high vacuum Diethylene glycol was dried and stored over 3 Aring MS

and aluminum oxide

Sodium tetrakis[35-bis(trifluoromethyl)phenyl]borate (60 micromol 10 equiv 54 mg) or Lithium tetrakis[35-

bis(trifluoromethyl)phenyl]borate (60 micromol 10 equiv 52 mg) diethylene glycol (180 micromol 30 equiv

173 microL) and anhydrous trimethyl orthoformate (120 micromol 20 equiv 133 microL) were dissolved in

anhydrous chloroform (6 mL) under inert atmosphere TFA stock solution (12 micromol 001 equiv 10 microL)

was added After equilibration of the reaction mixture 5 Aring MS was added The reaction progress was

monitored by 1H-NMR spectroscopy If needed more TFA stock solution was added Upon completion the

reaction was quenched by addition of triethylamine and the solvent was removed under reduced pressure

The crude product was purified by passing it over a short plug of silica gel The plug was rinsed with

anhydrous chloroform and removal of the solvent under reduced pressure gave the corresponding salts as

colourless solids

General Procedure B (NMR titrations)

Stock solutions of cryptand and NaBArF in CDCl3 were prepared The precise quantity of cryptand or metal

salt was determined with 14-dinitrobenzene as internal standard A cryptand stock solution with precise

concentration was prepared via dilution To the solution of metal salt cryptand stock solution was added to

keep the concentration of cryptand during the titration constant 600 microL of cryptand stock solution were

added to a standard NMR tube varying amounts of metal salt stock solution were added The titration was

monitored by 1H NMR spectroscopy (temperature 298 K) Binding constants were fitted using Bindfit All

raw data calculated fits and related data can be accessed via wwwsupramolecularorg

S4

2 Synthetic Procedures and Characterization Data

21 Synthesis of Orthoester Cryptates

Synthesis of o-(Hin)2-111

Diethylene glycol (36 mmol 30 equiv 345 microL) and trimethyl orthoformate

(24 mmol 20 equiv 265 microL) were dissolved in anhydrous chloroform (60 mL) under

inert atmosphere TFA (24 micromol 001 equiv 186 microL) was added After equilibration

of the reaction mixture 5 Aring MS was added The reaction progress was monitored by 1H-

NMR spectroscopy After 1 day more TFA (24 micromol 001 equiv 186 microL) was added

After 3 days in total the reaction was quenched by addition of triethylamine and the

solvent was removed under reduced pressure The crude product was purified by washing with diethyl ether

to give o-(Hin)2-111 as crystalline solid (206 mg 51)

1H-NMR (500 MHz CD3CN 298 K) δ (ppm) = 603 (s 2H c) 378 ndash 370 (m 12H b) 358 ndash 351 (m

12H a)

13C-NMR (125 MHz CD3CN 298 K) δ (ppm) = 1186 737 646

HRMS (ESI+) mz = 3611471 [M+Na]+ (calcd 3611469 for C14H26NaO9)

mp degradation gt250 degC

1H NMR spectrum (500 MHz CD3CN 298 K)

S5

13C NMR spectrum (125 MHz CD3CN 298 K)

1H NOE NMR spectrum (400 MHz CDCl3 298 K)

S6

Synthesis of [Li+o-(H)2-111]BArF-

The synthesis of [Li+o-(H)2-111]BArF- was reported

previously2 [Li+o-(H)2-111]BArF- was prepared

according to general procedure A The yield was improved

to 55 (40 mg)

Synthesis of o-(H)2-111

The synthesis of Synthesis of o-(H)2-111 was reported previously2

Synthesis of [Na+o-(H)2-111]BArF-

o-(H)2-111 (147 micromol 10 equiv 50 mg) was dissolved in

acetonitrile and NaBArF (147 micromol 10 equiv 131 mg)

was added The mixture was stirred for 5 min removal of the

solvent gave the product [Na+o-(H)2-111]BArF- as

colourless solid (181 mg quant)

1H-NMR (500 MHz CD2Cl2 298 K) δ (ppm) = 774 ndash 770

(m 8H) 758 ndash 755 (m 4H) 554 (s 2H c) 397 ndash 395 (m

12H b) 365 ndash 363 (m 12H a)

13C-NMR (125 MHz CD2Cl2 298 K) δ (ppm) = 1620 1616 1352 1283 1261 1239 1179 1179

1179 1178 1074 704 634

HRMS (ESI+) mz = 3611470 [M+Na]+ (calcd 3611469 for C14H26NaO9)

mp 182 degC

S4

2 Synthetic Procedures and Characterization Data

21 Synthesis of Orthoester Cryptates

Synthesis of o-(Hin)2-111

Diethylene glycol (36 mmol 30 equiv 345 microL) and trimethyl orthoformate

(24 mmol 20 equiv 265 microL) were dissolved in anhydrous chloroform (60 mL) under

inert atmosphere TFA (24 micromol 001 equiv 186 microL) was added After equilibration

of the reaction mixture 5 Aring MS was added The reaction progress was monitored by 1H-

NMR spectroscopy After 1 day more TFA (24 micromol 001 equiv 186 microL) was added

After 3 days in total the reaction was quenched by addition of triethylamine and the

solvent was removed under reduced pressure The crude product was purified by washing with diethyl ether

to give o-(Hin)2-111 as crystalline solid (206 mg 51)

1H-NMR (500 MHz CD3CN 298 K) δ (ppm) = 603 (s 2H c) 378 ndash 370 (m 12H b) 358 ndash 351 (m

12H a)

13C-NMR (125 MHz CD3CN 298 K) δ (ppm) = 1186 737 646

HRMS (ESI+) mz = 3611471 [M+Na]+ (calcd 3611469 for C14H26NaO9)

mp degradation gt250 degC

1H NMR spectrum (500 MHz CD3CN 298 K)

S5

13C NMR spectrum (125 MHz CD3CN 298 K)

1H NOE NMR spectrum (400 MHz CDCl3 298 K)

S6

Synthesis of [Li+o-(H)2-111]BArF-

The synthesis of [Li+o-(H)2-111]BArF- was reported

previously2 [Li+o-(H)2-111]BArF- was prepared

according to general procedure A The yield was improved

to 55 (40 mg)

Synthesis of o-(H)2-111

The synthesis of Synthesis of o-(H)2-111 was reported previously2

Synthesis of [Na+o-(H)2-111]BArF-

o-(H)2-111 (147 micromol 10 equiv 50 mg) was dissolved in

acetonitrile and NaBArF (147 micromol 10 equiv 131 mg)

was added The mixture was stirred for 5 min removal of the

solvent gave the product [Na+o-(H)2-111]BArF- as

colourless solid (181 mg quant)

1H-NMR (500 MHz CD2Cl2 298 K) δ (ppm) = 774 ndash 770

(m 8H) 758 ndash 755 (m 4H) 554 (s 2H c) 397 ndash 395 (m

12H b) 365 ndash 363 (m 12H a)

13C-NMR (125 MHz CD2Cl2 298 K) δ (ppm) = 1620 1616 1352 1283 1261 1239 1179 1179

1179 1178 1074 704 634

HRMS (ESI+) mz = 3611470 [M+Na]+ (calcd 3611469 for C14H26NaO9)

mp 182 degC

S5

13C NMR spectrum (125 MHz CD3CN 298 K)

1H NOE NMR spectrum (400 MHz CDCl3 298 K)

S6

Synthesis of [Li+o-(H)2-111]BArF-

The synthesis of [Li+o-(H)2-111]BArF- was reported

previously2 [Li+o-(H)2-111]BArF- was prepared

according to general procedure A The yield was improved

to 55 (40 mg)

Synthesis of o-(H)2-111

The synthesis of Synthesis of o-(H)2-111 was reported previously2

Synthesis of [Na+o-(H)2-111]BArF-

o-(H)2-111 (147 micromol 10 equiv 50 mg) was dissolved in

acetonitrile and NaBArF (147 micromol 10 equiv 131 mg)

was added The mixture was stirred for 5 min removal of the

solvent gave the product [Na+o-(H)2-111]BArF- as

colourless solid (181 mg quant)

1H-NMR (500 MHz CD2Cl2 298 K) δ (ppm) = 774 ndash 770

(m 8H) 758 ndash 755 (m 4H) 554 (s 2H c) 397 ndash 395 (m

12H b) 365 ndash 363 (m 12H a)

13C-NMR (125 MHz CD2Cl2 298 K) δ (ppm) = 1620 1616 1352 1283 1261 1239 1179 1179

1179 1178 1074 704 634

HRMS (ESI+) mz = 3611470 [M+Na]+ (calcd 3611469 for C14H26NaO9)

mp 182 degC

S6

Synthesis of [Li+o-(H)2-111]BArF-

The synthesis of [Li+o-(H)2-111]BArF- was reported

previously2 [Li+o-(H)2-111]BArF- was prepared

according to general procedure A The yield was improved

to 55 (40 mg)

Synthesis of o-(H)2-111

The synthesis of Synthesis of o-(H)2-111 was reported previously2

Synthesis of [Na+o-(H)2-111]BArF-

o-(H)2-111 (147 micromol 10 equiv 50 mg) was dissolved in

acetonitrile and NaBArF (147 micromol 10 equiv 131 mg)

was added The mixture was stirred for 5 min removal of the

solvent gave the product [Na+o-(H)2-111]BArF- as

colourless solid (181 mg quant)

1H-NMR (500 MHz CD2Cl2 298 K) δ (ppm) = 774 ndash 770

(m 8H) 758 ndash 755 (m 4H) 554 (s 2H c) 397 ndash 395 (m

12H b) 365 ndash 363 (m 12H a)

13C-NMR (125 MHz CD2Cl2 298 K) δ (ppm) = 1620 1616 1352 1283 1261 1239 1179 1179

1179 1178 1074 704 634

HRMS (ESI+) mz = 3611470 [M+Na]+ (calcd 3611469 for C14H26NaO9)

mp 182 degC

S7

1H NMR spectrum (500 MHz CD2Cl2 298 K)

13C NMR spectrum (125 MHz CD2Cl2 298 K)

S8

22 Interconversion of orthoformate cryptands

i) Self-assembly of o-(Hin)2-111 See Section 21 Synthesis of Orthoester Cryptates

ii) Self-assembly of [Li+o-(H)2-111]BArF- and attempted self-assembly of [Na+o-(H)2-111]BArF-

See General Procedure A and Section 21 Synthesis of Orthoester Cryptates

iii) Conversion of o-(Hin)2-111 to [Li+o-(H)2-111]BArF- o-(Hin)2-111 (60 micromol 10 equiv) was

stirred in CHCl3 (6 mL) with lithium tetrakis[35-bis(trifluoromethyl)phenyl]borate (60 micromol 10 equiv)

and TFA stock solution (12 micromol 001 equiv 10 microL) for 10 min The reaction was quenched by addition

of triethylamine and the solvent was removed under reduced The crude product was purified by passing it

over a short plug of silica gel The plug was rinsed with anhydrous acetonitrile and removal of the solvent

under reduced pressure gave the product as colourless solid

iv) Attempted conversion of o-(Hin)2-111 to [Na+o-(H)2-111]BArF- o-(Hin)2-111 (60 micromol

10 equiv) was stirred in CHCl3 (6 mL) with sodium tetrakis[35-bis(trifluoromethyl)phenyl]borate

(60 micromol 10 equiv) and TFA stock solution (12 micromol 001 equiv 10 microL) for 3 d The reaction progress

was monitored by 1H-NMR spectroscopy and no conversion was observed

v) Conversion of o-(H)2-111 cryptand to o-(Hin)2-111 o-(H)2-111 (6 micromol 10 equiv) was dissolved in

CHCl3 (6 mL) TFA stock solution (012 micromol 001 equiv 1 microL) was added The reaction mixture was left

standing without stirring for 10 min The reaction was quenched by addition of triethylamine and the solvent

was removed under reduced pressure to give the product as colourless solid

vi) Removal of metal salts [Na+o-(H)2-111]BArF- or [Li+o-(H)2-111]BArF- (60 micromol 10 equiv)

was stirred in CHCl3 (6 mL) with chloride-loaded anion exchange resin (Lewatit MP-68) for 12 h The resin

was removed by filtration and the solvent was removed under reduced pressure to give the product as

colourless oil

vii) Reintroduction of metals o-(H)2-111 (60 micromol 10 equiv) was stirred in CH3CN (6 mL) with sodium

or lithium tetrakis[35-bis(trifluoromethyl)phenyl]borate (60 micromol 10 equiv) for 5 min Removal of the

solvent under reduced pressure gave the products as colourless solids

S8

22 Interconversion of orthoformate cryptands

i) Self-assembly of o-(Hin)2-111 See Section 21 Synthesis of Orthoester Cryptates

ii) Self-assembly of [Li+o-(H)2-111]BArF- and attempted self-assembly of [Na+o-(H)2-111]BArF-

See General Procedure A and Section 21 Synthesis of Orthoester Cryptates

iii) Conversion of o-(Hin)2-111 to [Li+o-(H)2-111]BArF- o-(Hin)2-111 (60 micromol 10 equiv) was

stirred in CHCl3 (6 mL) with lithium tetrakis[35-bis(trifluoromethyl)phenyl]borate (60 micromol 10 equiv)

and TFA stock solution (12 micromol 001 equiv 10 microL) for 10 min The reaction was quenched by addition

of triethylamine and the solvent was removed under reduced The crude product was purified by passing it

over a short plug of silica gel The plug was rinsed with anhydrous acetonitrile and removal of the solvent

under reduced pressure gave the product as colourless solid

iv) Attempted conversion of o-(Hin)2-111 to [Na+o-(H)2-111]BArF- o-(Hin)2-111 (60 micromol

10 equiv) was stirred in CHCl3 (6 mL) with sodium tetrakis[35-bis(trifluoromethyl)phenyl]borate

(60 micromol 10 equiv) and TFA stock solution (12 micromol 001 equiv 10 microL) for 3 d The reaction progress

was monitored by 1H-NMR spectroscopy and no conversion was observed

v) Conversion of o-(H)2-111 cryptand to o-(Hin)2-111 o-(H)2-111 (6 micromol 10 equiv) was dissolved in

CHCl3 (6 mL) TFA stock solution (012 micromol 001 equiv 1 microL) was added The reaction mixture was left

standing without stirring for 10 min The reaction was quenched by addition of triethylamine and the solvent

was removed under reduced pressure to give the product as colourless solid

vi) Removal of metal salts [Na+o-(H)2-111]BArF- or [Li+o-(H)2-111]BArF- (60 micromol 10 equiv)

was stirred in CHCl3 (6 mL) with chloride-loaded anion exchange resin (Lewatit MP-68) for 12 h The resin

was removed by filtration and the solvent was removed under reduced pressure to give the product as

colourless oil

vii) Reintroduction of metals o-(H)2-111 (60 micromol 10 equiv) was stirred in CH3CN (6 mL) with sodium

or lithium tetrakis[35-bis(trifluoromethyl)phenyl]borate (60 micromol 10 equiv) for 5 min Removal of the

solvent under reduced pressure gave the products as colourless solids

S9

3 Experimental Binding Studies

The NMR titrations were carried out according to general procedure B

Ka [M-1] Fit error [M-1] avg Ka [M-1] u [M-1] U95 [M-1]

NaBArF

(1 mM)

500

500

400

30

20

10

500 30 plusmn100

Table S1 Association constants obtained for the titration of o-(H)2-111 with NaBArF in CDCl3 at 298 K Fit method

Nelder-Mead Binding model 11 u standard uncertainty = sradic119899 s standard deviation n number of measurements

U 95 confidence interval = t(0052) u t(α n-1) student-t distribution at a probability α3

NaBArF 1 mM httpappsupramolecularorgbindfitview292f7428-60d2-4ada-ae82-027f57613cfe

NaBArF 1 mM httpappsupramolecularorgbindfitview53fee8f7-156d-474b-b9d2-568f3128ec79

NaBArF 1 mM httpappsupramolecularorgbindfitview77054cde-c218-4d67-8d19-

2b8eef99546e

Table S2 Links to raw data calculated fits and statistical information for the titrations

Figure S1 Representative partial 1H NMR (500 MHz 298 K CDCl3) stack plot for a titration of o-

(H)2-111 with NaBArF from 0-149

149

135

129

118

104

89

67

60

49

45

39

30

27

24

20

18

14

10

9

6

4

2

0

S10

Figure S2 Left Binding isotherm and species concentration plot for titration of o-(H)2-111 (1 mM) with NaBArF

in CDCl3 at 298 K Black dots Experimental points Blue line Fit according to 11 model orange und grey lines mole

fractions of corresponding species Right Residual plot

Figure S3 Left Binding isotherm and species concentration plot for titration of o-(H)2-111 (1 mM) with NaBArF

in CDCl3 at 298 K Black dots Experimental points Blue line Fit according to 11 model orange und grey lines mole

fractions of corresponding species Right Residual plot

Figure S4 Left Binding isotherm and species concentration plot for titration of o-(H)2-111 (1 mM) with NaBArF

in CDCl3 at 298 K Black dots Experimental points Blue line Fit according to 11 model orange und grey lines mole

fractions of corresponding species Right Residual plot

00

02

04

06

08

10

12

525

530

535

540

545

550

0 05 1 15

Mo

lefr

acti

on

s

δ[p

pm

]

[Na+]0[o-(H)2-111]0

-0010

-0005

0000

0005

0010

0015

0 05 1 15

δ[p

pm

]

[Na+]0[o-(H)2-111]0

00

02

04

06

08

10

12

525

530

535

540

545

550

0 05 1 15

Mo

lefr

acti

on

s

δ[p

pm

]

[Na+]0[o-(H)2-111]0

-0015

-0010

-0005

0000

0005

0010

0015

0 05 1 15

δ[p

pm

]

[Na+]0[o-(H)2-111]0

00

02

04

06

08

10

12

525

530

535

540

545

550

0 05 1 15

Mo

lefr

acti

on

s

δ[p

pm

]

[Na+]0[o-(H)2-111]0

-0015

-0010

-0005

0000

0005

0010

0015

0 05 1 15

δ[p

pm

]

[Na+]0[o-(H)2-111]0

S11

4 Crystallographic Data

Compound o-(Hin)2-111

Empirical formula C14H26O9

Formula weight 33835

TemperatureK 15000(10)

Crystal system monoclinic

Space group P21c

aAring 149352(5)

bAring 820386(19)

cAring 149002(4)

αdeg 90

βdeg 113530(4)

γdeg 90

VolumeAring3 167387(9)

Z 4

ρcalcgcm3 1343

μmm‑1 0959

F(000) 7280

Crystal sizemm3 0228 x 0197 x 0168

Radiation CuKα (λ = 154184)

2Θ range for data collectiondeg 1195 to 148172

Index ranges -18 le h le 13 -10 le k le 8 -14 le l le 18

Reflections collected 10016

Independent reflections 3329 [Rint = 00338 Rsigma = 00264]

Datarestraintsparameters 33290209

Goodness-of-fit on F2 1054

Final R indexes [Igt=2σ (I)] R1 = 00357 wR2 = 00980

Final R indexes [all data] R1 = 00434 wR2 = 01039

Largest diff peakhole e Aring-3 026-021

o-(Hin)2-111 was crystallized by slow evaporation of a solution of o-(Hin)2-111 in diethyl ether The cif-

file was deposited in the Cambridge structural database under identifier CCDC 1876094

S12

Compound [Na+o-(H)2-111]BArF-

Empirical formula C46H38BF24NaO9

Formula weight 122456

TemperatureK 14995(10)

Crystal system orthorhombic

Space group P212121

aAring 131390(3)

bAring 177561(3)

cAring 217663(5)

αdeg 90

βdeg 90

γdeg 90

VolumeAring3 507800(19)

Z 4

ρcalcgcm3 1602

μmm‑1 0174

F(000) 24720

Crystal sizemm3 02282 x 01705 x 00955

Radiation MoKα (λ = 071073)

2Θ range for data collectiondeg 5538 to 591

Index ranges -13 le h le 17 -24 le k le 24 -27 le l le 26

Reflections collected 67161

Independent reflections 12798 [Rint = 00419 Rsigma = 00356]

Datarestraintsparameters 12798481861

Goodness-of-fit on F2 1030

Final R indexes [Igt=2σ (I)] R1 = 00454 wR2 = 00941

Final R indexes [all data] R1 = 00649 wR2 = 01040

Largest diff peakhole e Aring-3 065-033

Flack parameter -008(12)

[Na+o-(H)2-111]BArF- was crystallized by solvent layering of hexane over solution of [Na+o-(H)2-

111]BArF- in chloroform The cif-file was deposited in the Cambridge structural database under identifier

CCDC 1876120

S11

4 Crystallographic Data

Compound o-(Hin)2-111

Empirical formula C14H26O9

Formula weight 33835

TemperatureK 15000(10)

Crystal system monoclinic

Space group P21c

aAring 149352(5)

bAring 820386(19)

cAring 149002(4)

αdeg 90

βdeg 113530(4)

γdeg 90

VolumeAring3 167387(9)

Z 4

ρcalcgcm3 1343

μmm‑1 0959

F(000) 7280

Crystal sizemm3 0228 x 0197 x 0168

Radiation CuKα (λ = 154184)

2Θ range for data collectiondeg 1195 to 148172

Index ranges -18 le h le 13 -10 le k le 8 -14 le l le 18

Reflections collected 10016

Independent reflections 3329 [Rint = 00338 Rsigma = 00264]

Datarestraintsparameters 33290209

Goodness-of-fit on F2 1054

Final R indexes [Igt=2σ (I)] R1 = 00357 wR2 = 00980

Final R indexes [all data] R1 = 00434 wR2 = 01039

Largest diff peakhole e Aring-3 026-021

o-(Hin)2-111 was crystallized by slow evaporation of a solution of o-(Hin)2-111 in diethyl ether The cif-

file was deposited in the Cambridge structural database under identifier CCDC 1876094

S12

Compound [Na+o-(H)2-111]BArF-

Empirical formula C46H38BF24NaO9

Formula weight 122456

TemperatureK 14995(10)

Crystal system orthorhombic

Space group P212121

aAring 131390(3)

bAring 177561(3)

cAring 217663(5)

αdeg 90

βdeg 90

γdeg 90

VolumeAring3 507800(19)

Z 4

ρcalcgcm3 1602

μmm‑1 0174

F(000) 24720

Crystal sizemm3 02282 x 01705 x 00955

Radiation MoKα (λ = 071073)

2Θ range for data collectiondeg 5538 to 591

Index ranges -13 le h le 17 -24 le k le 24 -27 le l le 26

Reflections collected 67161

Independent reflections 12798 [Rint = 00419 Rsigma = 00356]

Datarestraintsparameters 12798481861

Goodness-of-fit on F2 1030

Final R indexes [Igt=2σ (I)] R1 = 00454 wR2 = 00941

Final R indexes [all data] R1 = 00649 wR2 = 01040

Largest diff peakhole e Aring-3 065-033

Flack parameter -008(12)

[Na+o-(H)2-111]BArF- was crystallized by solvent layering of hexane over solution of [Na+o-(H)2-

111]BArF- in chloroform The cif-file was deposited in the Cambridge structural database under identifier

CCDC 1876120

S12

Compound [Na+o-(H)2-111]BArF-

Empirical formula C46H38BF24NaO9

Formula weight 122456

TemperatureK 14995(10)

Crystal system orthorhombic

Space group P212121

aAring 131390(3)

bAring 177561(3)

cAring 217663(5)

αdeg 90

βdeg 90

γdeg 90

VolumeAring3 507800(19)

Z 4

ρcalcgcm3 1602

μmm‑1 0174

F(000) 24720

Crystal sizemm3 02282 x 01705 x 00955

Radiation MoKα (λ = 071073)

2Θ range for data collectiondeg 5538 to 591

Index ranges -13 le h le 17 -24 le k le 24 -27 le l le 26

Reflections collected 67161

Independent reflections 12798 [Rint = 00419 Rsigma = 00356]

Datarestraintsparameters 12798481861

Goodness-of-fit on F2 1030

Final R indexes [Igt=2σ (I)] R1 = 00454 wR2 = 00941

Final R indexes [all data] R1 = 00649 wR2 = 01040

Largest diff peakhole e Aring-3 065-033

Flack parameter -008(12)

[Na+o-(H)2-111]BArF- was crystallized by solvent layering of hexane over solution of [Na+o-(H)2-

111]BArF- in chloroform The cif-file was deposited in the Cambridge structural database under identifier

CCDC 1876120

S13

Analysis of intramolecular hydrogen bonds in o-(Hin)2-111

entry Compound H⋯O distance [Aring] C-H⋯O angles [deg] O-C-O angle [deg]

1 o-(Hin)2-111 24 24 24 25

25 25

1195 1195 1206

1211 1220 1223

10748 10758 10767

10774 10791 10822 Table S3 H⋯O distances C-H⋯O angles and O-C-O angles derived from solid state structure of o-(Hin)2-111

Analysis of M+-O distances O-C-O angles and R-C-O-M torsion angles in orthoformate and

orthoacetate cryptands

entry Compound M+-O distance [Aring]

(orthoester

oxygens)

M+-O

distance

[Aring]

(chain

oxygens)

O-C-O angle [deg] Torsion angle R-C-

O-M [deg]

1 [Na+o-(H)2-

111] BArF-

2242(5) 2512(3)

2553(3) 2553(3)

2677(3) 3606(4)

2433(3)

2445(3)

2592(3)

1043(3) 1049(3)

1074(3) 1077(3)

1116(3) 1167(4)

151(2) 159(2)

171(4) 173(2)

175(4) 176(4)

2 ref4 [Na+o-(CH3)2-

111] BArF-

- - - 1793 1795 1797

1797 1798 1799

3 ref 2 [Li+o-(H)2-

111]BArF-

1957(5) 1963(5)

2940(5) 3157(5)

3620(5) 3672(5)

2163(5)

2176(6)

2232(5)

1059(2) 1064(2)

1104(2) 1109(3)

1121(3) 1122(2)

1331 1378 1451

1530 1580 1586

4 ref1 [K+o-(CH3)2-

211] BArF-

- - - 1789 1790 1791

1794 1794 1800

5 ref1 [Rb+o-(CH3)2-

221] BArF-

- - - 1780 1780 1788

1788 1792 1792

6 ref1 [Cs+o-(CH3)2-

221] BArF-

- - - 1781 1782 1789

1790 1792 1792

Table S4 Comparison of M+-O distances O-C-O angles and torsion angles in orthoformate and orthoacetate

cryptands

Graph 1 Comparison of R-C-O-M torsion angles of orthoformate and orthoacetate cryptands124

S14

5 References

1 O Shyshov R C Brachvogel T Bachmann R Srikantharajah D Segets F Hampel R Puchta

and M von Delius Angew Chem Int Ed 2017 56 776ndash781

2 H Loumlw E Mena-Osteritz and M von Delius Chem Sci 2018 9 4785ndash4793

3 D Brynn Hibbert and P Thordarson Chem Commun 2016 52 12792ndash12805

4 R-C Brachvogel F Hampel and M von Delius Nat Commun 2015 6 7129