Site-Selective Oxidation and Metal-Induced 2-Propynylation of Pyranose Derivatives en route to Tetrodotoxins

Lidia Ozores; Fernando Cagide; Ricardo Alonso

doi:10.1055/s-2004-835651

LETTER

Site-Selective Oxidation and Metal-Induced 2-Propynylation of Pyranose Derivatives en route to Tetrodotoxins

Lidia Ozores, Fernando Cagide, Ricardo Alonso*
Departamento de Química Orgánica y Unidad asociada al C.S.I.C., Universidad de Santiago, 15782 Santiago de Compostela, Spain
Fax: +34(981)591014; e-Mail: qoraa@usc.es;

Abstract

All articles of this category

Abstract

The radical-based site-selective oxidation of 2-hydroxyethyl acetals and the metal(Zn,Ti)-induced 2-propynylation of aldehydes can both be carried out successfully on highly functionalized oxygenated substrates, as demonstrated in the context of a synthetic plan for tetrodotoxin and its analogues, for which promising synthetic intermediates were prepared from d-mannopyranoses.

Key words

radical oxidation - acetal hydrolyses - aldehyde addition - 2-propynylation - tetrodotoxin

Full Text

References

1 Du Bois and Hinman recently completed a total synthesis of enantiomerically pure tetrodotoxin: Hinman A. Du Bois J. J. Am. Chem. Soc. 2003, 125: 11510

Besides Du Bois (ref. ¹), Isobe and co-workers also completed (for the first time) a total synthesis of tetrodotoxin in enantiomeric pure form:

2a Ohyabu N. Nishikawa T. Isobe M. J. Am. Chem. Soc. 2003, 125: 8798

2b The same group has just published an improved synthesis: Nishikawa T. Urabe D. Isobe M. Angew. Chem. Int. Ed. 2004, 43: 4782

Kishi first reported a racemic total synthesis of tetrodotoxin:

3a Kishi Y. Aratani M. Fukuyama T. Nakatsubo F. Goto T. J. Am. Chem. Soc. 1972, 94: 9217

3b Kishi Y. Fukuyama T. Aratani M. Nakatsubo F. Goto T. J. Am. Chem. Soc. 1972, 94: 9219

Other synthetic efforts toward tetrodotoxin include:

4a Ohtani Y. Shinada T. Ohfune Y. Synlett 2003, 619

4b Taber DF. Storck PH. J. Org. Chem. 2003, 68: 7768

4c Itoh T. Watanabe M. Fukuyama T. Synlett 2002, 1323

4d Noya B. Paredes MD. Ozores L. Alonso R. J. Org. Chem. 2000, 65: 5960

4e Fraser-Reid B. Burgey CS. Vollerthun R. Pure Appl. Chem. 1998, 70: 285 ; and references therein

5 Zottola MA. Alonso R. Vite GD. Fraser-Reid B. J. Org. Chem. 1989, 54: 6123

6 Noya B. Alonso R. Tetrahedron Lett. 1997, 38: 2745

7a Ogawa T. Sasajima K. Carbohydr. Res. 1981, 93: 53

7b Koto S. Inada S. Yoshida T. Toyama M. Zen S. Can. J. Chem. 1981, 59: 255

8 Du Y. Zhang M. Kong F. Org. Lett. 2000, 2: 3797

9

Preparation of C6-Sugar Aldehydes of Type III (Route C : 7 → 8 → IIIc). Selected Data of Allyl 2,4-Bis- O -Benzoyl-3-keto-6- O -trytil-β- d -mannopyranoside ( 8): ¹H NMR (250 MHz, CDCl₃, TMS): δ = 8.22-8.18 (m, 2 H, ArH), 7.87-7.84 (m, 2 H, ArH), 7.69-7.12 (m, 21 H, ArH), 6.18 (d, J = 10.4 Hz, 1 H, CH), 6.00-5.85 (m, 1 H, OCH₂CHCH₂), 5.47 (d, J = 1.9 Hz, 1 H, CH), 5.40-5.23 (m, 3 H, OCH₂CHCH ₂ + CH), 4.39-4.25 (m, 2 H, OCH ₂CHCH₂), 4.19-4.13 (m, 1 H, CH), 3.60 (dd, J = 10.4 Hz, J = 1.6 Hz, 1 H, CH₂), 3.33 (dd, J = 10.4 Hz, J = 3.8 Hz, 1 H, CH₂). ¹³C NMR and DEPT (63 MHz): δ = 195.2 (CO), 164.5 (2 × CO), 143.5 (Ar), 133.8 (CH), 133.3 (CH), 132.6 (CH), 130.1 (CH), 129.9 (CH), 128.8 (Ar), 128.73 (CH), 128.70 (Ar), 128.5 (CH), 128.2 (CH), 127.8 (CH), 126.9 (CH), 118.5 (OCH₂CHCH₂), 98.4 (CH), 86.6 (C), 76.6 (CH), 72.53 (CH), 72.47 (CH), 68.5 (CH₂), 61.8 (CH₂). [α]_D ²⁵ +12.0 (c 1.2, CHCl₃).
Allyl 2,4-Bis- O -Benzoyl-3-benzyloximino-6- O -trytil-β- d -mannopyranoside: ¹H NMR (250 MHz, CDCl₃, TMS): δ = 8.16-8.12 (m, 2 H, ArH), 7.86-7.83 (m, 2 H, ArH), 7.64-7.07 (m, 26 H, ArH), 6.49 (d, J = 1.4 Hz, 1 H, CH), 6.12 (d, J = 10.2 Hz, 1 H, CH), 6.00-5.87 (m, 1 H, OCH₂CHCH₂), 5.36-5.21 (m, 3 H, OCH₂CHCH ₂ + CH), 5.03 (s, 2 H, NOCH ₂Ar), 4.32-4.25 (m, 2 H, OCH ₂CHCH₂), 4.16-4.08 (m, 1 H, CH), 3.46 (dd, J = 10.3 Hz, J = 1.9 Hz, 1 H, CH₂), 3.30 (dd, J = 10.3 Hz, J = 4.2 Hz, 1 H, CH₂). ¹³C NMR and DEPT (63 MHz): δ = 165.1 (CO), 164.7 (CO), 146.9 (CNOBn), 143.6 (Ar), 137.3 (Ar), 133.4 (CH), 133.2 (CH), 132.9 (CH), 130.0 (CH), 129.8 (CH), 129.5 (Ar), 129.2 (Ar), 128.5 (CH), 128.1 (CH), 128.0 (CH), 127.7 (CH), 127.5 (CH), 126.8 (CH), 117.8 (OCH₂CHCH₂), 96.7 (CH), 86.4 (C), 76.5 (NOCH₂Ar), 71.5 (CH), 68.1 (CH₂), 66.1 (CH), 64.7 (CH), 62.0 (CH₂). [α]_D ²⁵ -11.2 (c 1.2, CHCl₃).
Allyl 2,4-Bis- O -Benzoyl-3-benzyloximino-β- d -mannopyranoside: ¹H NMR (250 MHz, CDCl₃, TMS): δ = 8.10-8.07 (m, 4 H, ArH), 7.66-7.26 (m, 11 H, ArH), 6.50 (d, J = 1.6 Hz, 1 H, CH), 6.05 (d, J = 10.0 Hz, 1 H, CH), 6.01-5.87 (m, 1 H, OCH₂CHCH₂), 5.38-5.24 (m, 2 H, OCH₂CHCH ₂), 5.19 (d, J = 1.3 Hz, 1 H, CH), 5.11 (s, 2 H, NOCH ₂Ar), 4.36-4.07 (m, 3 H, OCH ₂CHCH₂ + CH), 3.93-3.80 (m, 2 H, CH₂). ¹³C NMR and DEPT (63 MHz): δ = 165.4 (CO), 165.0 (CO), 146.6 (CNOBn), 137.2 (Ar), 133.5 (CH), 133.4 (CH), 133.0 (CH), 129.9 (CH), 129.3 (Ar), 129.0 (Ar), 128.5 (CH), 128.4 (CH), 128.2 (CH), 128.1 (CH), 127.6 (CH), 118.0 (OCH₂CHCH₂), 96.9 (CH), 76.6 (NOCH₂Ar), 72.1 (CH), 68.3 (CH₂), 65.6 (CH), 64.6 (CH), 61.6 (CH₂). MS (IQ⁺ low resolution): m/z (%) = 532 (94) [M⁺ + 1], 474 (100) [M⁺ - OAllyl], 410 (71) [M⁺ - Obz]. [α]_D ²⁵ -25.1 (c 1.2, CHCl₃).
1- O -Allyl-2,4-Bis- O -Benzoyl-3-deoxy-3-benzyloxyimino-6-aldehydo-β- d -arabino-hexopyranose (IIIc): ¹H NMR (250 MHz, CDCl₃, TMS): δ = 9.76 (d, J = 1.2 Hz, 1 H, CHO), 8.08-8.05 (m, 4 H, ArH), 7.64-7.44 (m, 6 H, ArH), 7.26-7.21 (m, 5 H, ArH), 6.46 (d, J = 1.4 Hz, 1 H, CH), 6.10 (d, J = 10.2 Hz, 1 H, CH), 5.88-6.04 (m, 1 H, OCH₂CHCH₂), 5.37-5.24 (m, 2 H, OCH₂CHCH ₂), 5.09 (s, 2 H, NOCH ₂Ar), 5.06-5.02 (m, 1 H, CH), 4.55 (d, J = 11.0 Hz, 1 H, CH), 4.33-4.15 (m, 2 H, OCH ₂CHCH₂). ¹³C NMR and DEPT (63 MHz): δ = 195.7 (CHO), 170.5 (CO), 164.9 (CO), 145.2 (CNOBn), 141.8 (CH), 136.9 (Ar), 133.3 (CH), 132.6 (CH), 131.8 (CH), 129.97 (Ar), 129.95 (CH), 129.91 (Ar), 128.5 (CH), 128.4 (CH), 128.2 (CH), 128.1 (CH), 127.9 (CH), 127.7 (CH), 118.4 (OCH₂CHCH₂), 97.0 (CH), 76.8 (NOCH₂Ar), 74.5 (CH), 68.8 (CH₂), 64.9 (CH), 64.2 (CH). [α]_D ²⁵ -17.5 (c 1.2, CHCl₃).

10a Suárez and co-workers recently reported on the synthesis of chiral spiroacetals from carbohydrates under similar conditions: Martín A. Salazar JA. Suárez E. J. Org. Chem. 1996, 61: 3999

10b For the transformation of fully acetate-protected d-glucosyl halides into spiroorthoesters, see: Praly JP. Descotes G. Tetrahedron Lett. 1982, 23: 849

11

Radical-Based Site-Selective Oxidation of Allyl Glycoside Derivatives into Anomeric Spiroorthoesters: 2-Hydroxyethyl 2,4-Bis- O -Benzoyl-3- O -( tert -butyldimethylsilyl)-6- O -trytil-β- d -mannopyranoside ( 9): To a solution of the allyl mannopyranoside 7 [8] (369 mg, 0.47 mmol) in acetone-H₂O (8:2), N-methyl morpholine oxide (54 mg, 0.52 mmol) and OsO₄ (cat.), were added. After one day at r.t., the solvent was removed under reduced pressure, the residue was redissolved in EtOH-H₂O (95:5). NaIO₄ (113 mg, 0.52 mmol) as an aq solution (1.1 mL) and NaBH₄ (20 mg, 0.52 mmol) were added. After 4 h at r.t., the reaction mixture was quenched by addition of dilute aq HCl and extracted with Et₂O. Chromatographic purification (EtOAc-hexane 20:80) afforded 9 (267 mg, 72%). ¹H NMR (250 MHz, CDCl₃, TMS): δ = 8.18-8.14 (m, 2 H, ArH), 7.87-7.83 (m, 2 H, ArH), 7.60-7.05 (m, 21 H, ArH), 5.65 (t, J = 9.7 Hz, 1 H, CH), 5.42-5.41 (m, 1 H, CH), 5.10 (s, 1 H, CH), 4.34 (dd, J = 9.4 Hz, J = 3.4 Hz, 1 H, CH), 4.17-4.09 (m, 1 H, CH), 3.97-3.79 (m, 4 H, 2 × CH₂), 3.31-3.29 (m, 2 H, CH₂), 0.62 [s, 9 H, SiC(CH₃)₃], 0.04 (s, 3 H, SiCH₃), -0.16 (s, 3 H, SiCH₃). ¹³C NMR and DEPT (63 MHz): δ = 166.1 (CO), 164.9 (CO), 143.6 (Ar), 133.2 (ArH), 132.8 (ArH), 129.9 (ArH), 129.71 (Ar), 129.69 (Ar), 129.6 (ArH), 128.5 (ArH), 128.4 (ArH), 128.1 (ArH), 127.6 (ArH), 126.7 (ArH), 98.3 (CH), 86.7 (C), 72.7 (CH), 70.8 (CH), 70.6 (CH₂), 69.7 (CH), 68.9 (CH), 62.6 (CH₂), 61.9 (CH₂), 25.2 [SiC(CH₃)₃], 17.5 [SiC(CH₃)₃], -4.8 (SiCH₃), -5.2 (SiCH₃). MS: m/z (%) = 485 (81) [M⁺ - CH₂CH₂OH - OCPh₃], 243 (51) [CPh₃ ⁺], 105 (100) [Bz⁺]. [α]_D ²⁵ -6.9 (c 1.2, CHCl₃).
Spiroorthoester 10: (Diacetoxy)iodobenzene (146 mg, 0.43 mmol) and I₂ (99 mg, 0.39 mmol) were added to a solution of the 2-hydroxyethyl mannopyranoside 9 (309 mg, 0.39 mmol) in cyclohexane (30 mL, 0.01 M) under argon. After irradiating with a 100 W sunlamp for 7 h, the reaction mixture was washed with a sat. aq solution of Na₂S₂O₃ and extracted with Et₂O. Column chromatography (EtOAc-hexane 10:90) afforded 10 (145 mg, 47%). ¹H NMR (250 MHz, CDCl₃, TMS): δ = 8.20-8.17 (m, 2 H, ArH), 7.87-7.84 (m, 2 H, ArH), 7.60-7.06 (m, 21 H, ArH), 5.74 (t, J = 10.0 Hz, 1 H, CH), 5.57 (d, J = 3.1 Hz, 1 H, CH), 4.35 (dd, J = 9.4 Hz, J = 3.1 Hz, 1 H, CH), 4.29-3.98 (m, 5 H, 2 × CH₂ + CH), 3.33-3.30 (m, 2 H, CH₂), 0.64 [s, 9 H, SiC(CH ₃)₃], 0.09 (s, 3 H, SiCH₃), -0.14 (s, 3 H, SiCH₃). ¹³C NMR and DEPT (63 MHz): δ = 165.8 (CO), 164.8 (CO), 143.8 (Ar), 133.0 (ArH), 132.8 (ArH), 130.0 (ArH), 129.9 (Ar), 129.8 (Ar), 129.6 (ArH), 128.6 (ArH), 128.4 (ArH), 128.1 (ArH), 127.6 (ArH), 126.7 (ArH), 117.4 (OCO), 86.5 (C), 72.7 (CH), 72.5 (CH), 70.9 (CH), 69.5 (CH), 65.2 (CH₂), 64.7 (CH₂), 62.7 (CH₂), 25.2 [SiC(CH₃)₃], 17.5 [SiC(CH₃)₃], -4.8 (SiCH₃), -5.2 (SiCH₃). MS (electron impact): m/z (%) = 730 (0.1) [M⁺ - C(CH₃)₃], 243 (100) [C(Ph)₃ ⁺], 165 (24), 105 (100) [Bz⁺]. MS (chemical ionization, CH₄): m/z (%) = 545 (11) [M⁺ - C(Ph)₃], 243 (100) [C(Ph)₃ ⁺]. [α]_D ²⁵ -19.3 (c 1.1, CHCl₃).

12 Alcaide B. Almendros P. Aragoncillo C. Org. Lett. 2000, 2: 1411

13a Anies C. Lallemamd J.-Y. Pancrazi A. Tetrahedron Lett. 1996, 37: 5519

13b Hiraoka H. Furuta K. Ikeda N. Yamamoto H. Bull. Chem. Soc. Jpn. 1984, 57: 2768

14 Harada N. Saito A. Ono H. Murai S. Li H.-Y. Gawronski J. Gawronska K. Sugioka T. Uda H. Enantiomer 1996, 1: 119

15

CCDC 244334 contains the supplementary crystallographic data for 16a. These data can be obtained free of charge via www.ccdc.cam.ac.uk/data_request/cif, by emailing data_request@ccdc.cam.ac.uk, or by contacting The Cambridge Crystallographic Data Centre, 12, Union Road, Cambridge CB2 1EZ, UK; fax: +44 (1223)336033.

16

Zn-Promoted 2-Propynylation of C6-Sugar Aldehydes: IIIc → 11:
Zn dust (80 mg, 1.21 mmol) and propargylic bromide (68 µL, 0.60 mmol) were added in two portions to aldehyde IIIc (54 mg, 0.10 mmol) in a mixture of THF and aq sat. NH₄Cl (1:5, 5 mL) at r.t. After 6 h at r.t. and 2 h at 70 °C, the reaction mixture was diluted with brine and extracted with EtOAc. Chromatography afforded 11 (37 mg, 64%). ¹H NMR (250 MHz, CDCl₃, TMS): δ = 8.09-8.05 (m, 4 H, ArH), 7.62-7.44 (m, 6 H, ArH), 7.26-7.21 (m, 5 H, ArH), 6.45 (d, J = 12.2 Hz, 1 H, CH), 6.10-6.06 (m, 1 H, CH), 6.05-5.90 (m, 1 H, OCH₂CHCH₂), 5.37-5.04 (m, 5 H, OCH₂CHCH ₂ + NOCH ₂Ar + CH), 4.39-4.31 (m, 2 H, OCH ₂CHCH₂), 4.14-4.09 (m, 2 H, 2 × CH), 2.62-2.60 (m, 2 H, CH₂), 2.05-2.04 (m, 1 H, CH). ¹³C NMR + DEPT (63 MHz): δ = 165.1 (CO), 165.0 (CO), 146.9 (CN), 146.3 (CN), 137.2 (Ar), 133.6 (ArH), 133.5 (ArH), 133.3 (ArH), 133.0 (ArH), 130.1 (ArH), 130.0 (ArH), 129.0 (Ar), 128.6 (Ar), 128.4 (ArH), 128.3 (ArH), 128.28 (ArH), 128.25 (ArH), 128.11 (ArH), 127.7 (ArH), 118.11 (OCH₂CHCH₂), 96.9 (CH), 96.7 (CH), 80.0 (C), 76.5 (CH₂), 73.0 (CH), 72.4 (CH), 71.4 (C), 70.6 (CH), 68.4 (CH₂), 67.8 (CH), 66.6 (CH), 65.9 (CH), 65.6 (CH₂), 64.6 (CH), 64.5 (CH), 22.7 (CH₂).

17

Ti-Promoted 2-Propynylation of C6-Sugar Aldehydes: 12 → 14 → 16:
t-BuLi (1.7 M, 1.5 mL, 2.67 mmol) was added to a solution of 3-(tetrahydro-2-pyranoxyl)-1-(trimethylsilyl)propyne (13a, 0.566 g, 2.67 mmol) in THF (3 mL) at -78 °C. Stirring for 0.5 h was followed by the addition of Ti(Oi-Pr)₄ (0.8 mL, 2.67 mmol), further stirring for 10 min, addition of a solution of 1,2:3,4-di-O-isopropyliden-α-d-galacto-hexodialdo-1,5-piranose (12, 355 mg, 1.37 mmol) in the same solvent and final stirring for 0.5 h at -78 °C. One hour after the reaction mixture reached r.t., aq HCl (0.1 M, 25 mL) was added. Extraction with Et₂O (3 × 50 mL) and final chromatography (20% EtOAc-hexane) rendered 14 (60%) in two fractions (fraction A: R _f = 0.39, 14a + 14c, 248 mg, 38% and fraction B: R _f = 0.58, 14b + 14d, 143 mg, 22%), which were subsequently seperately dissolved in acetone and treated with 2,2-dimethoxypropane (2 equiv) and p-TsOH (cat.) at r.t. for 0.5 h. Addition of Et₃N to reach a pH = 8 and final chromatography gave the acetonides 16a:16b:16c:16d (27:20:10:4). Compound 16a [(6 R ,7 R )-16]: ¹H NMR (500 MHz, CDCl₃): δ = 0.16 (s, 9 H, Si-CH₃) 1.32 (s, CH₃), 1.38 (s, CH₃), 1.38 (s, CH₃), 1.45 (s, CH₃), 1.54 (s, CH₃), 1.61 (s, CH₃), 4.06 (dd, J ₁ = 1.6 Hz, J ₂ = 9.3 Hz, 1 H, CH-5), 4.18 (dd, J ₁ = 4.8 Hz, J ₂ = 9.3 Hz, 1 H, CH-6), 4.30 (dd, J ₁ = 2.3 Hz, J ₂ = 4.9 Hz, 1 H, CH-2), 4.40 (dd, J ₁ = 1.7 Hz, J ₂ = 7.9 Hz, 1 H, CH-4), 4.63 (dd, J ₁ = 2.3 Hz, J ₂ = 7.9 Hz, 1 H, CH-3), 4.85 (d, J = 4.8 Hz, 1 H, CH-7-C≡C-TMS), 5.50 (d, J = 4.8 Hz, 1 H, CH-1). ¹³C NMR and DEPT (75 MHz, CDCl₃): δ = 0.37 (SiCH₃), 25.02 (CH₃), 25.41 (CH₃), 26.48 (CH₃), 26.69 (CH₃), 27.19 (CH₃), 28.06 (CH₃), 67.13 (CH), 69.39 (CH), 70.89 (CH), 71.08 (CH), 71.55 (CH), 76.18 (CH), 94.13 (C), 96.37 (CH), 101.92 (C), 109.07 (C), 109.58 (C), 110.33 (C). For the X-ray data of 16a see ref. [15] ; [α]_D ²⁰ -20.1 (c 1.6, CHCl₃); mp 132 °C. Compound 16b [(6 S ,7 S )-16]: ¹H NMR (250 MHz, CDCl₃): δ = 0.17 (s, 9 H, Si-CH₃) 1.33 (s, 9 H, 2 CH₃), 1.39 (s, 2 CH₃), 1.46 (s, CH₃), 1.58 (s, 9 H, CH₃), 4.12 (dd, J ₁ = 1.5 Hz, J ₂ = 8.6 Hz, 1 H, CH), 4.28 (dd, J ₁ = 5.3 Hz, J ₂ = 8.5 Hz, 1 H, CH), 4.35 (dd, J ₁ = 2.6 Hz, J ₂ = 5.0 Hz, 1 H, CH), 4.44 (dd, J ₁ = 1.6 Hz, J ₂ = 7.9 Hz, 1 H, CH), 4.60 (dd, J ₁ = 2.3 Hz, J ₂ = 7.9 Hz, 1 H, CH), 4.85 (d, J = 4.8 Hz, 1 H, OCH), 5.50 (d, J = 4.8 Hz, 1 H, OCH-C≡C-TMS). ¹³C NMR and DEPT (63 MHz, CDCl₃): δ = 0.38 (SiCH₃), 25.12 (CH₃), 25.48 (CH₃), 26.43 (CH₃), 26.63 (CH₃), 26.93 (CH₃), 28.25 (CH₃), 67.42 (CH), 69.36 (CH), 70.64 (CH), 71.25 (CH), 71.28 (CH), 77.59 (C), 92.81 (C), 96.73 (CH), 96.82 (C), 102.81 (C), 109.27 (C), 110.18 (C), 111.49 (C). Compound 16c [(6 R ,7 S )-16]: ¹H NMR (500 MHz, CDCl₃): δ = 0.15 (s, 9 H, Si-CH₃), 1.32 (s, CH₃), 1.38 (s, CH₃), 1.41 (s, CH₃), 1.48 (s, CH₃), 1.50 (s, CH₃), 1.60 (s, CH₃), 3.59 (d, J = 9.1 Hz, 1 H, CH), 4.30-4.37 (m, 3 H, CH), 4.63 (dd, J ₁ = 2.3 Hz, J ₂ = 7.9 Hz, 1 H, CH), 4.79 (d, J = 2.4 Hz, 1 H, OCH-C≡C-TMS), 5.51 (d, J = 4.9 Hz, 1 H, CH). ¹³C NMR (75 MHz, CDCl₃): δ = 0.38 (SiCH₃), 24.87 (CH₃), 25.41 (CH₃), 26.31 (CH₃), 26.47 (CH₃), 27.36 (CH₃), 28.70 (CH₃), 68.75 (CH), 69.62 (CH), 69.67 (CH), 70.93 (CH), 71.14 (CH), 80.47 (CH), 91 (C), 96.77 (CH), 105 (C), 109.19 (C), 109.99 (C), 113 (C). [α]_D ²⁰ -110.24 (c 0.26, CHCl₃).