1

Supplementary Material for

Introduction of Axial Chirality at a Spiro Carbon Atom in Synthesis of a Pentaerythritol – Imine MacrocyclesJ. Grajewski,a K. Piotrowska,a M. Zgorzelak,a U. Rychlewska,a A. Janiak,a K. Biniek-Antosiaka, and J. Gawronskia

Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry.This journal is © The Royal Society of Chemistry 2018

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Table of Contents

Figure S1. Eight unique conformational permutations of the structure of A, including enantiomers..........3

Figure S2. An illustration of asymmetric unit of 9 together with labelling scheme. .....................................4

Figure S3. An overlay of the molecules of 9 obtained from the crystal structure (blue) and the gas phase calculations (magenta). .................................................................................................................................5

Figure S4. Top (a) and side (b) space-fill view of molecular arrangement in the crystals of 9. .....................6

Table S1. Comparison of selected torsion angles describing molecular conformation of 9 as present in crystals with the one calculated at the B3LYP/6-311g(d,p) level in the gas phase. ......................................7

Table S2. C-H…O intermolecular interactions in the crystals of 9. ................................................................8

Table S3. Crystal data, structure refinement parameters for compound 9. .................................................9

Spectra of 3 .................................................................................................................................................10

Spectra of 5 .................................................................................................................................................12

HRMS Spectrum of 7 ...................................................................................................................................16

Spectra of 8 .................................................................................................................................................18

Spectra of 9 .................................................................................................................................................20

Figure S5. Experimental CD spectra of 9. (solid line), calculated (dashed line) and calculated for a diastereoisomer of 9 (dotted line) with opposite (P) helicity of both spiro fragments (not found in reaction). .....................................................................................................................................................25

Figure S6. Calculated structure of diastereoisomer of 9 with opposite (P) helicity (not found in reaction). .....................................................................................................................................................26

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Figure S1. Eight unique conformational permutations of the structure of 1, including enantiomers.

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Crystal structure

Figure S2. An illustration of asymmetric unit of 9 together with labelling scheme. Ellipsoids are drawn at the 40% probability level, hydrogen atoms are represented by spheres of arbitrary radii.

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Figure S3. An overlay of the molecules of 9 obtained from the crystal structure (blue) and the gas phase calculations (magenta).

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Packing in crystals of 9

The rotational behavior of spiroacetal rhombimine 9 in crystal largely depends on the strong intermolecular C-H∙∙∙O hydrogen bonding interactions. The interactions cause partial interpenetration of the neighbouring molecules, as illustrated in Fig. S4. The angle between two interpenetrating rings amounts to 76.5°. Geometrical parameters describing these interactions are listed in Table S2.

Figure S4. Top (a) and side (b) space-fill view of molecular arrangement in the crystals of 9. Each macrocycle uses the spiro unit to partially penetrate the cavity of its neighbour. c) C-H...O interactions between two adjacent molecules.

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Table S1. Comparison of selected torsion angles describing molecular conformation of 9 as present in crystals with the one calculated at the B3LYP/6-311g(d,p) level in the gas phase.

X-ray Calculated

N1-C1-C2-N2 -70.8(3) -63.9

C1-C2-N2-C7 106.5(3) 125.9

N2-C7-C8-C9 3.3(5) 179.9

C7-C8-C9-C10 174.9(3) -175.7

C8-C9-C10-C11 1.0(6) 0.7

C9-C10-C11-C14 -175.7(3) 180

C10-C11-C14-O1 -165.4(3) -7.2

C11-C14-O1-C15 176.5(3) 178.8

C14-O2-C15-C17 -56.8(4) 57.8

O2-C15-C17-C18 -171.7(3) -173.6

C15-C17-C18-O3 -172.7(3) -172.1

C17-C18-O3-C20 59.3(4) 57.2

C18-O3-C20-C21 175.8(3) 179.4

O3-C20-C21-C22 14.5(4) -137.4

C20-C21-C22-C23 -179.0(3) -177.1

C21-C22-C23-C24 -0.4(5) 0.2

C22-C23-C24-C27 179.2(3) 179.0

C23-C24-C27-N3 -169.4(3) 2.6

C24-C27-N3-C28 179.7(3) -179.7

C27-N3-C28-C29 127.5(3) 121.9

N3-C28-C29-N4 -62.2(4) -63.9

C28-C29-N4-C34 103.3(4) 125.9

C29-N4-C34-C35 177.0(3) 179.9

N4-C34-C35-C36 -4.4(5) 4.9

C34-C35-C36-C37 179.0(3) 179.1

C35-C36-C37-C38 1.3(5) 0.5

C36-C37-C38-C41 -175.4(3) 179.4

C37-C38-C41-O5 -138.8(3) 173.4

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C38-C41-O5-C42 -173.4(2) 178.8

C41-O5-C42-C44 57.9(3) 57.8

O5-C42-C44-C45 -177.1(2) -173.6

C42-C44-C45-O7 -174.4(2) -172.1

C44-C45-O7-C47 57.3(3) 57.2

C45-O7-C47-C48 -177.1(2) 179.4

O7-C47-C48-C49 -96.5(3) 45.0

C47-C48-C49-C50 169.8(3) 176.9

C48-C49-C50-C51 -1.3(5) 0.2

C49-C50-C51-C54 -172.4(3) -179.1

C50-C51-C54-N1 -3.3(5) -177.9

C51-C54-N1-C1 176.2(3) -179.7

C54-N1-C1-C2 98.7(3) 122.0

Table S2. C-H…O intermolecular interactions in the crystals of 9.C-H (Å) H…O (Å) C…O (Å) C-H…O (°) Symm

C14-H14…O4 1.00 2.64 3.638(4) 172 x-1/2, -y+3/2, -z+1

C42-H42B…O6 0.99 2.22 3.193(4) 166 x+1/2, -y+1/2, -z+1

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Table S3. Crystal data, structure refinement parameters for compound 9.9

Chemical formula C54H60N4O8Mr 893.06

Crystal system, space group

Orthorhombic, P212121

Temperature (K) 150

a, b, c (Å) 10.7257 (2), 11.3249 (2), 39.4835 (5)

V (Å3) 4795.96 (14)

Z 4

Radiation type Cu Kα

Μ (mm-1) 0.67

Crystal size (mm) 0.30 × 0.20 × 0.12

Diffractometer SuperNova

Absorption correction

Multi-scan

Tmin, Tmax 0.846, 1.000

No. of measured, independent and observed [I > 2σ(I)] reflections

20339, 9822, 9564

Rint 0.026

(sin θ/λ)max (Å-1) 0.631

R[F2 > 2σ(F2)], wR(F2), S

0.049, 0.134, 1.07

No. of reflections 9822

No. of parameters 595

H-atom treatment H-atom parameters constrained

max, min (e Å-3) 0.56, -0.25

Absolute structure parameter

0.24 (10)

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1H and 13C NMR spectra were recorded on a Bruker 400 MHz or Varian Mercury 300 MHz at ambient temperature. All 1H NMR spectra are reported in parts per million (ppm) downfield of TMS and were measured relative to the signals for CDCl3 (7.27 ppm). All 13C NMR spectra were reported in ppm relative to residual CDCl3 (77.0 ppm) and were obtained with 1H decoupling. MS spectra were recorded on impact HD Bruker apparatus.

Spectra of 3

OB

O

O

OBO

O

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)

-200

0

200

400

600

800

1000

1200

1400

1600

1800

2000

2200

2400

2600

2800

3000

3200

3400

8.00

4.13

4.05

2.00

-0.0

0

1.56

4.11

7.26

7.85

7.86

7.86

7.87

7.88

7.88

7.95

7.95

7.96

7.97

10.0

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1H NMR (400 MHz, CDCl3 + TMS)

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0102030405060708090100110120130140150160170180190f1 (ppm)

-2000

0

2000

4000

6000

8000

10000

12000

14000

16000

18000

20000

22000

24000

26000

28000

30000

32000

34000

36000

38000-0.0

01.

02

29.7

0

36.6

6

64.9

3

76.6

877

.00

77.3

2

115.

87

128.

71

134.

44

138.

06

192.

71

13C NMR (100 MHz, CDCl3+ TMS):

MS spectra – ionization EI, positive mode

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Spectra of 5

N

N N

NBO

O

OB

O

BO

O

OB

O

1H NMR (400 MHz, CDCl3):

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13C NMR (100 MHz,CDCl3):

MS spectra – ionization EI, positive mode

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HSQC spectrum of 5 (upper panel) and zoom (lower panel)

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NOESY spectrum of 5 (upper panel) and zoom (lower panel)

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HRMS Spectrum of 7

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1H NMR of 7

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Spectra of 8

O

O

O

O

O

O

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0(ppm)

2.0

4.0

2.0

2.0

4.0

4.0

2.0

0.00

3.68

3.72

3.85

3.86

3.89

3.90

4.83

4.84

4.87

4.88

5.53

7.26

7.65

7.68

7.89

7.89

7.90

7.91

7.92

7.92

10.0

3

1H NMR (300 MHz, CDCl3)

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0102030405060708090100110120130140150160170180190200(ppm)

0.00

32.6

3

70.5

170

.99

76.6

177

.04

77.2

377

.45

101.

22

126.

8112

9.73

136.

78

143.

78

191.

94

13C NMR (75 MHz, CDCl3)

MS spectra – ionization EI, positive mode

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Spectra of 9

N

N N

NO

O

O

O

O

O

O

O

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.5(ppm)

4.0

4.0

8.0

4.0

4.0

8.0

8.0

4.0

-0.0

0

1.49

1.59

1.88

3.34

3.37

3.58

3.61

3.76

3.78

3.78

3.79

3.80

4.74

4.76

5.40

7.26

7.39

7.41

7.52

7.54

8.14

1H NMR (400 MHz, CDCl3)

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0102030405060708090100110120130140150160(ppm)

0.00

24.4

9

32.5

132

.70

70.4

670

.88

73.7

076

.70

77.0

277

.22

77.3

4

101.

89

126.

3812

7.80

136.

83

139.

77

161.

04

13C NMR (100 MHz, CDCl3)

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HSQC spectrum of 9 (CDCl3)

Expansion of HSQC spectrum of 9 (CDCl3)

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COSY spectrum of 9 (CDCl3)

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HRMS spectra of 9 – ionization ESI, positive mode

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Figure S5. Experimental CD spectra of 9. (solid line), calculated (dashed line) and calculated for a diastereoisomer of 9 (dotted line) with opposite (P) helicity of both spiro fragments (not found in reaction). Main pattern of Cotton effects remains the same due to similar arrangement of phenyl and imine groups, slight red shift and increase of magnitude can be observed.

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Figure S6. Calculated structure of diastereoisomer of 9 with opposite (P) helicity (not found in reaction).