Matthias W. Büttner, Jennifer B. Nätscher, Christian Burschka, and Reinhold Tacke *

Transcription

1 Development of a New Building Block for the Synthesis of Silicon-Based Drugs and Odorants: Alternative Synthesis of the Retinoid Agonist Disila-bexarotene Matthias W. Büttner, Jennifer B. Nätscher, Christian Burschka, and Reinhold Tacke * Universität Würzburg, Institut für Anorganische Chemie, Am Hubland, D Würzburg, Germany Supporting Information * To whom correspondence should be addressed. Phone: Fax: r.tacke@mail.uni-wuerzburg.de. S1

2 Figure S1. Molecular structure of 5 in the crystal (probability level of displacement ellipsoids 50%). Figure S2. Molecular structures of the two crystallographically independent molecules in the crystal of 6 (probability level of displacement ellipsoids 50%). S2

3 Table S1. Crystal data and structure refinement for 5. Identification code 5 Empirical formula C 19 H 33 BO 2 Si 2 Formula weight Temperature Wavelength 193(2) K Å Crystal system, space group Monoclinic, P2 1 /c Unit cell dimensions a = (19) Å = 90 deg. b = (15) Å = (12) deg. c = (12) Å = 90 deg. Volume (4) Å 3 Z, Calculated density 4, Mg/m 3 Absorption coefficient mm 1 F(000) 784 Crystal size range for data collection 0.5 x 0.5 x 0.4 mm 3.08 to deg. Limiting indices -20 h 20, -17 k 17, -14 l 14 Reflections collected / unique / 5141 [R(int) = ] Completeness to = % Absorption correction None Refinement method Full-matrix least-squares on F 2 Data / restraints / parameters 5141 / 0 / 226 Goodness-of-fit on F Final R indices [I>2(I)] R1 = , wr2 = R indices (all data) R1 = , wr2 = Largest diff. peak and hole and e Å 3 S3

4 Table S2. Atomic coordinates (x 10 4 ) and equivalent isotropic displacement parameters (Å 2 x 10 3 ) for 5. U(eq) is defined as one third of the trace of the orthogonalized Uij tensor. x y z U(eq) Si1 4292(1) 5619(1) 7074(1) 30(1) Si2 2529(1) 6872(1) 7708(1) 28(1) B 1879(1) 4160(1) 2843(1) 26(1) O1 2596(1) 3656(1) 2667(1) 36(1) O2 1093(1) 4047(1) 1848(1) 36(1) C1 4750(1) 4319(2) 7564(2) 56(1) C2 4947(1) 6231(2) 6128(2) 48(1) C3 4395(1) 6401(2) 8531(2) 47(1) C4 3551(1) 6366(2) 8971(2) 42(1) C5 1511(1) 6890(1) 8244(2) 42(1) C6 2749(2) 8186(1) 7251(2) 54(1) C7 2342(1) 6020(1) 6285(1) 25(1) C8 3069(1) 5512(1) 6041(1) 24(1) C9 2866(1) 4912(1) 4941(1) 25(1) C (1) 4806(1) 4067(1) 24(1) C (1) 5318(1) 4318(1) 26(1) C (1) 5900(1) 5424(1) 27(1) C13 310(1) 5280(2) 3429(2) 41(1) C (1) 3023(1) 1535(1) 34(1) C (1) 3573(1) 813(1) 34(1) C (2) 1963(1) 1997(2) 51(1) C (1) 2978(2) 843(2) 47(1) C18 561(1) 2892(2) 70(2) 53(1) C (2) 4440(1) -28(2) 47(1) S4

5 Table S3. Bond lengths [Å] and angles [deg] for 5. Si1-C (19) Si1-C (19) Si1-C (17) Si1-C (14) Si2-C (18) Si2-C (19) Si2-C (18) Si2-C (14) B-O (18) B-O (19) B-C (19) O1-C (16) O2-C (18) C3-C (2) C7-C (19) C7-C (18) C8-C (18) C9-C (18) C10-C (19) C11-C (19) C11-C (19) C14-C (2) C14-C (2) C14-C (2) C15-C (2) C15-C (2) C2-Si1-C (11) C2-Si1-C (9) C1-Si1-C (10) C2-Si1-C (7) C1-Si1-C (8) C3-Si1-C (7) C5-Si2-C (9) C5-Si2-C (8) C6-Si2-C (10) C5-Si2-C (7) C6-Si2-C (7) C4-Si2-C (7) O2-B-O (12) O2-B-C (13) O1-B-C (12) B-O1-C (11) B-O2-C (12) C4-C3-Si (12) C3-C4-Si (12) C12-C7-C (12) C12-C7-Si (10) C8-C7-Si (10) C9-C8-C (12) C9-C8-Si (10) C7-C8-Si (10) C8-C9-C (12) C9-C10-C (12) C9-C10-B (12) C11-C10-B (12) C12-C11-C (12) C12-C11-C (13) C10-C11-C (12) C11-C12-C (12) S5

6 O1-C14-C (13) O1-C14-C (12) C17-C14-C (15) O1-C14-C (11) C17-C14-C (14) C16-C14-C (15) O2-C15-C (14) O2-C15-C (13) C18-C15-C (15) O2-C15-C (11) C18-C15-C (15) C19-C15-C (14) S6

7 Table S4. Anisotropic displacement parameters (Å 2 x 10 3 ) for 5. The anisotropic displacement factor exponent takes the form: -2 2 [ h 2 a* 2 U h k a* b* U12 ] U11 U22 U33 U23 U13 U12 Si1 25(1) 36(1) 25(1) -6(1) 2(1) 1(1) Si2 35(1) 27(1) 23(1) -6(1) 10(1) -1(1) B 29(1) 27(1) 22(1) -2(1) 6(1) -3(1) O1 34(1) 43(1) 25(1) -13(1) 3(1) 4(1) O2 32(1) 47(1) 25(1) -12(1) 4(1) -2(1) C1 46(1) 48(1) 57(1) 4(1) -8(1) 12(1) C2 34(1) 66(1) 44(1) -8(1) 13(1) -10(1) C3 33(1) 70(1) 34(1) -22(1) 5(1) -5(1) C4 38(1) 60(1) 24(1) -9(1) 5(1) 1(1) C5 44(1) 50(1) 34(1) -8(1) 17(1) 2(1) C6 87(2) 31(1) 52(1) -10(1) 33(1) -11(1) C7 29(1) 23(1) 21(1) 0(1) 6(1) 1(1) C8 26(1) 25(1) 20(1) -1(1) 5(1) 0(1) C9 26(1) 26(1) 23(1) -3(1) 6(1) 1(1) C10 28(1) 23(1) 19(1) 0(1) 6(1) -2(1) C11 25(1) 28(1) 22(1) 1(1) 4(1) 0(1) C12 27(1) 29(1) 24(1) -1(1) 7(1) 4(1) C13 26(1) 57(1) 33(1) -10(1) 1(1) 2(1) C14 44(1) 33(1) 23(1) -9(1) 9(1) -1(1) C15 40(1) 37(1) 23(1) -9(1) 7(1) -5(1) C16 84(1) 31(1) 38(1) -3(1) 22(1) 5(1) C17 49(1) 55(1) 39(1) -14(1) 18(1) 1(1) C18 51(1) 62(1) 38(1) -20(1) 3(1) -16(1) C19 68(1) 42(1) 27(1) -1(1) 10(1) 3(1) S7

8 Table S5. Hydrogen coordinates (x 10 4 ) and isotropic displacement parameters (Å 2 x 10 3 ) for 5. x y z U(eq) H1A H1B H1C H2A H2B H2C H3A H3B H4A H4B H5A H5B H5C H6A H6B H6C H H H13A H13B H13C H16A H16B H16C H17A H17B H17C H18A H18B H18C H19A H19B H19C S8

9 Table S6. Torsion angles [deg] for 5. O2-B-O1-C (17) C10-B-O1-C (13) O1-B-O2-C (17) C10-B-O2-C (13) C2-Si1-C3-C (15) C1-Si1-C3-C (17) C8-Si1-C3-C (17) Si1-C3-C4-Si (18) C5-Si2-C4-C (12) C6-Si2-C4-C (15) C7-Si2-C4-C (14) C5-Si2-C7-C (13) C6-Si2-C7-C (14) C4-Si2-C7-C (12) C5-Si2-C7-C (12) C6-Si2-C7-C (14) C4-Si2-C7-C (13) C12-C7-C8-C9-0.06(19) Si2-C7-C8-C (10) C12-C7-C8-Si (10) Si2-C7-C8-Si1-0.24(17) C2-Si1-C8-C (13) C1-Si1-C8-C (14) C3-Si1-C8-C (12) C2-Si1-C8-C (13) C1-Si1-C8-C (14) C3-Si1-C8-C7 4.62(15) C7-C8-C9-C10 1.2(2) Si1-C8-C9-C (10) C8-C9-C10-C11-1.0(2) C8-C9-C10-B (13) O2-B-C10-C (13) O1-B-C10-C9 4.5(2) O2-B-C10-C11 3.1(2) O1-B-C10-C (13) C9-C10-C11-C (19) B-C10-C11-C (13) C9-C10-C11-C (14) B-C10-C11-C13 1.1(2) C10-C11-C12-C7 1.6(2) C13-C11-C12-C (14) C8-C7-C12-C11-1.3(2) Si2-C7-C12-C (11) B-O1-C14-C (14) B-O1-C14-C (16) B-O1-C14-C (15) B-O2-C15-C (15) B-O2-C15-C (15) B-O2-C15-C (15) O1-C14-C15-O (14) C17-C14-C15-O (13) C16-C14-C15-O (14) O1-C14-C15-C (14) C17-C14-C15-C (18) C16-C14-C15-C (19) O1-C14-C15-C (15) C17-C14-C15-C (19) C16-C14-C15-C (13) S9

10 Table S7. Crystal data and structure refinement for 6. Identification code 6 Empirical formula C 13 H 22 OSi 2 Formula weight Temperature Wavelength 173(2) K Å Crystal system, space group Triclinic, P1 Unit cell dimensions a = (18) Å = 92.22(3) deg. b = (2) Å = (3) deg. c = (3) Å = (3) deg. Volume (5) Å 3 Z, Calculated density 4, Mg/m 3 Absorption coefficient mm 1 F(000) 544 Crystal size range for data collection 0.3 x 0.3 x 0.1 mm 2.27 to deg. Limiting indices -12 h 12, -13 k 13, -21 l 21 Reflections collected / unique / 6771 [R(int) = ] Completeness to = % Absorption correction None Refinement method Full-matrix least-squares on F 2 Data / restraints / parameters 6771 / 0 / 301 Goodness-of-fit on F Final R indices [I>2(I)] R1 = , wr2 = R indices (all data) R1 = , wr2 = Largest diff. peak and hole and e Å 3 S10

11 Table S8. Atomic coordinates (x 10 4 ) and equivalent isotropic displacement parameters (Å 2 x 10 3 ) for 6. U(eq) is defined as one third of the trace of the orthogonalized Uij tensor. x y z U(eq) Si1 6409(1) 4093(1) 1361(1) 38(1) Si2 8331(1) 1924(1) 557(1) 33(1) C1 4499(3) 3250(3) 1466(2) 65(1) C2 6710(3) 5848(3) 1729(2) 55(1) C3 6610(3) 3910(3) 253(1) 58(1) C4 6613(3) 2478(3) -14(1) 57(1) C5 8088(3) 114(2) 392(2) 57(1) C (3) 2717(2) 168(1) 47(1) C7 8641(2) 2415(2) 1705(1) 27(1) C8 7864(2) 3302(2) 2022(1) 26(1) C9 8178(2) 3596(2) 2892(1) 25(1) C (2) 3032(2) 3434(1) 23(1) C (2) 2151(2) 3139(1) 26(1) C (2) 1887(2) 2276(1) 29(1) C (2) 1488(2) 3731(1) 39(1) O1 9464(1) 3301(1) 4290(1) 27(1) Si (1) 9102(1) 3418(1) 27(1) Si (1) 6882(1) 2824(1) 27(1) O (1) 5179(1) 4735(1) 28(1) C (3) 10129(2) 4364(1) 42(1) C (3) 9326(2) 2513(2) 47(1) C (2) 9534(2) 3141(1) 35(1) C (2) 8558(2) 2459(1) 36(1) C (2) 6873(2) 3558(1) 41(1) C (2) 5660(2) 1917(1) 39(1) C (2) 6440(2) 3392(1) 23(1) C (2) 7339(2) 3656(1) 23(1) C (2) 6899(2) 4095(1) 23(1) C (2) 5616(2) 4284(1) 22(1) C (2) 4694(2) 4017(1) 22(1) C (2) 5139(2) 3578(1) 24(1) C (2) 3296(2) 4203(1) 30(1) S11

12 Table S9. Bond lengths [Å] and angles [deg] for 6. Si1-C (3) Si1-C (3) Si1-C (2) Si1-C (2) Si2-C (3) Si2-C (2) Si2-C (3) Si2-C (19) C3-C (4) C7-C (3) C7-C (2) C8-C (2) C9-C (3) C10-O (2) C10-C (2) C11-C (3) C11-C (3) Si21-C (2) Si21-C (2) Si21-C (2) Si21-C (18) Si22-C (2) Si22-C (2) Si22-C (2) Si22-C (2) O21-C (2) C23-C (3) C27-C (2) C27-C (2) C28-C (3) C29-C (2) C30-C (2) C31-C (3) C31-C (2) C1-Si1-C (13) C1-Si1-C (14) C2-Si1-C (14) C1-Si1-C (12) C2-Si1-C (10) C3-Si1-C (10) C4-Si2-C (13) C4-Si2-C (14) C6-Si2-C (12) C4-Si2-C (9) C6-Si2-C (10) C5-Si2-C (11) C4-C3-Si (2) C3-C4-Si (17) C12-C7-C (16) C12-C7-Si (13) C8-C7-Si (15) C9-C8-C (18) C9-C8-Si (13) C7-C8-Si (13) C10-C9-C (16) C9-C10-O (15) C9-C10-C (16) O1-C10-C (16) C12-C11-C (17) S12

13 C12-C11-C (17) C10-C11-C (17) C11-C12-C (17) C22-Si21-C (11) C22-Si21-C (11) C23-Si21-C (10) C22-Si21-C (9) C23-Si21-C (9) C21-Si21-C (9) C26-Si22-C (10) C26-Si22-C (10) C25-Si22-C (11) C26-Si22-C (9) C25-Si22-C (9) C24-Si22-C (9) C24-C23-Si (14) C23-C24-Si (14) C32-C27-C (16) C32-C27-Si (13) C28-C27-Si (13) C29-C28-C (16) C29-C28-Si (13) C27-C28-Si (14) C30-C29-C (15) O21-C30-C (15) O21-C30-C (15) C29-C30-C (16) C32-C31-C (16) C32-C31-C (15) C30-C31-C (16) C31-C32-C (16) S13

14 Table S10. Anisotropic displacement parameters (Å 2 x 10 3 ) for 6. The anisotropic displacement factor exponent takes the form: -2 2 [ h 2 a* 2 U h k a* b* U12 ] U11 U22 U33 U23 U13 U12 Si1 37(1) 51(1) 25(1) -6(1) -3(1) 24(1) Si2 36(1) 36(1) 28(1) -8(1) 7(1) 9(1) C1 34(1) 88(2) 68(2) -16(2) -1(1) 22(1) C2 74(2) 55(2) 39(1) -1(1) -6(1) 40(1) C3 70(2) 85(2) 26(1) 0(1) -1(1) 52(2) C4 51(1) 87(2) 31(1) -22(1) -4(1) 29(1) C5 74(2) 43(1) 52(1) -14(1) 21(1) 3(1) C6 54(1) 50(1) 40(1) 3(1) 19(1) 11(1) C7 26(1) 26(1) 29(1) -2(1) 7(1) 3(1) C8 25(1) 29(1) 24(1) -4(1) 4(1) 6(1) C9 23(1) 27(1) 27(1) -1(1) 4(1) 8(1) C10 21(1) 24(1) 24(1) -1(1) 3(1) 3(1) C11 21(1) 25(1) 33(1) 1(1) 4(1) 5(1) C12 27(1) 26(1) 36(1) -3(1) 9(1) 8(1) C13 34(1) 46(1) 41(1) 5(1) 3(1) 21(1) O1 26(1) 31(1) 24(1) -1(1) 0(1) 11(1) Si21 33(1) 20(1) 30(1) 3(1) 7(1) 5(1) Si22 25(1) 29(1) 26(1) 3(1) 3(1) 8(1) O21 23(1) 26(1) 32(1) -1(1) 0(1) 8(1) C21 48(1) 25(1) 48(1) 0(1) -1(1) 4(1) C22 58(1) 35(1) 52(1) 11(1) 26(1) 1(1) C23 44(1) 26(1) 37(1) 4(1) 5(1) 13(1) C24 38(1) 34(1) 33(1) 8(1) 1(1) 12(1) C25 32(1) 54(1) 39(1) 6(1) 9(1) 13(1) C26 36(1) 39(1) 35(1) -1(1) -2(1) 4(1) C27 24(1) 22(1) 24(1) 1(1) 6(1) 4(1) C28 25(1) 22(1) 22(1) 2(1) 6(1) 5(1) C29 22(1) 22(1) 26(1) -1(1) 6(1) 3(1) C30 21(1) 23(1) 22(1) 1(1) 5(1) 8(1) C31 23(1) 20(1) 25(1) 1(1) 8(1) 5(1) C32 22(1) 23(1) 27(1) 1(1) 5(1) 3(1) C33 30(1) 22(1) 39(1) 4(1) 9(1) 6(1) S14

15 Table S11. Hydrogen coordinates (x 10 4 ) and isotropic displacement parameters (Å 2 x 10 3 ) for 6. x y z U(eq) H1A H1B H1C H2A H2B H2C H3A H3B H4A H4B H5A H5B H5C H6A H6B H6C H H H13A H13B H13C H H H21A H21B H21C H22A H22B H22C H23A H23B H24A H24B H25A H25B H25C H26A H26B H26C H H H33A H33B H33C S15

16 Table S12. Torsion angles [deg] for 6. C1-Si1-C3-C4-67.4(2) C2-Si1-C3-C (18) C8-Si1-C3-C4 50.7(2) Si1-C3-C4-Si2-67.3(2) C6-Si2-C4-C3-72.0(2) C5-Si2-C4-C (18) C7-Si2-C4-C3 47.2(2) C4-Si2-C7-C (16) C6-Si2-C7-C (17) C5-Si2-C7-C (18) C4-Si2-C7-C (19) C6-Si2-C7-C (17) C5-Si2-C7-C (17) C12-C7-C8-C9-0.1(3) Si2-C7-C8-C (13) C12-C7-C8-Si (13) Si2-C7-C8-Si1 0.9(2) C1-Si1-C8-C (17) C2-Si1-C8-C (18) C3-Si1-C8-C (16) C1-Si1-C8-C (18) C2-Si1-C8-C (17) C3-Si1-C8-C7-16.6(2) C7-C8-C9-C10-1.1(3) Si1-C8-C9-C (13) C8-C9-C10-O (16) C8-C9-C10-C11 0.8(3) C9-C10-C11-C12 0.7(2) O1-C10-C11-C (15) C9-C10-C11-C (17) O1-C10-C11-C13 2.5(2) C10-C11-C12-C7-1.9(3) C13-C11-C12-C (18) C8-C7-C12-C11 1.6(3) Si2-C7-C12-C (14) C22-Si21-C23-C (17) C21-Si21-C23-C (14) C28-Si21-C23-C (16) Si21-C23-C24-Si (17) C26-Si22-C24-C (15) C25-Si22-C24-C (17) C27-Si22-C24-C (17) C26-Si22-C27-C (16) C25-Si22-C27-C (16) C24-Si22-C27-C (13) C26-Si22-C27-C (15) C25-Si22-C27-C (16) C24-Si22-C27-C (17) C32-C27-C28-C29-0.8(2) Si22-C27-C28-C (12) C32-C27-C28-Si (12) Si22-C27-C28-Si21-3.7(2) C22-Si21-C28-C (16) C23-Si21-C28-C (13) C21-Si21-C28-C (16) C22-Si21-C28-C (16) C23-Si21-C28-C (16) C21-Si21-C28-C (15) C27-C28-C29-C30-1.0(2) Si21-C28-C29-C (12) C28-C29-C30-O (14) S16

17 C28-C29-C30-C31 2.4(2) O21-C30-C31-C (14) C29-C30-C31-C32-2.0(2) O21-C30-C31-C33-1.3(2) C29-C30-C31-C (15) C30-C31-C32-C27 0.2(2) C33-C31-C32-C (15) C28-C27-C32-C31 1.2(2) Si22-C27-C32-C (13) S17