Stereoselective Preparation
of Cyclopropylmagnesium Reagents via a Br-Mg
Exchange Using i-PrMgCl×LiCl
in the Presence of Dioxane

Christian B. Rauhut; Christian Cervino; Arkady Krasovskiy; Paul Knochel

doi:10.1055/s-0028-1087487

Subscribe to RSS

Please copy the URL and add it into your RSS Feed Reader.

https://www.thieme-connect.de/rss/thieme/en/10.1055-s-00000083.xml

Share / Bookmark

Facebook X Linkedin Weibo

Download PDF

Synlett 2009(1): 67-70
DOI: 10.1055/s-0028-1087487

LETTER

Stereoselective Preparation of Cyclopropylmagnesium Reagents via a Br-Mg Exchange Using i-PrMgCl×LiCl in the Presence of Dioxane

Christian B. Rauhut, Christian Cervino, Arkady Krasovskiy, Paul Knochel*
Department Chemie und Biochemie, Ludwig-Maximilians-Universität München, Butenandtstraße 5-13, 81377 München, Germany
Fax: +49(89)218077680; e-Mail: Paul.Knochel@cup.uni-muenchen.de;

Further Information

Publication History

Received 30 September 2008
Publication Date:
12 December 2008 (online)

Abstract
Full Text
References

Permissions and Reprints All articles of this category

Abstract

The reaction of various cyclopropyl bromides with i-PrMgCl˙LiCl in THF-dioxane provides the corresponding magnesiated cyclopropane reagents with complete retention of configuration.

Key words

Grignard reactions - organometallic reagents - stereoselectivity - copper - carbocycles

References and Notes

1a Silverman GS. Rakita PE. In Handbook of Grignard Reagents Marcel Dekker; New York: 1996.

Google Scholar
1b Wakefield BJ. In Organomagnesium Methods in Organic Synthesis Academic Press; London: 1995.

Google Scholar
1c Grignard Reagents: New Developments Richey HG. Wiley; New York: 1999.

Google Scholar
2 Knochel P. Dohle W. Gommermann N. Kneisel FF. Kopp F. Korn T. Sapountzis I. Vu VA. Angew. Chem. Int. Ed. 2003, 42: 4302

Crossref PubMed Google Scholar
3a Lisko JR. Jones WM. Organometallics 1985, 4: 944

Google Scholar
3b Hackett M. Whitesides GM. J. Am. Chem. Soc. 1988, 110: 1449

Google Scholar
3c Wakamatsu H. Isono N. Mori M. J. Org. Chem. 1997, 62: 8917

Google Scholar
3d Trofimov A. Rubina M. Rubin M. Gevorgyan V. J. Org. Chem. 2007, 72: 8910

Google Scholar
4a de Meijere A. Wessjohann L. Synlett 1990, 20

Google Scholar
4b de Meijere A. Hopf H. Chem. Rev. 2006, 106: 4785

Google Scholar
4c Brackmann F. de Meijere A. Chem. Rev. 2007, 107: 4493

Google Scholar
5 Abramovitch A. Fensterbank L. Malacria M. Marek I. Angew. Chem. Int. Ed. 2008, 47: 6865

Crossref Google Scholar
6a Rieke RD. Science 1989, 246: 1260

Google Scholar
6b Rieke RD. Hanson MV. Tetrahedron 1997, 53: 1925

Google Scholar
6c Lee J. Velarde-Ortiz R. Guijarro A. Wurst JR. Rieke RD. J. Org. Chem. 2000, 65: 5428

Google Scholar
6d Piller FM. Appukkuttan P. Gavryushin A. Helm M. Knochel P. Angew. Chem. Int. Ed. 2008, 47: 6802

Google Scholar
7a Knochel P. Dohle W. Gommermann N. Kneisel FF. Kopp F. Korn T. Sapountzis I. Vu V.-V. Angew. Chem. Int. Ed. 2003, 42: 4302

Google Scholar
7b Krasovskiy A. Knochel P. Angew. Chem. Int. Ed. 2004, 43: 3333

Google Scholar
7c Kopp F. Knochel P. Org. Lett. 2007, 9: 1639

Google Scholar
7d Kopp F. Wunderlich S. Knochel P. Chem. Commun. 2007, 2075

Google Scholar
8 Krasovskiy A. Straub BF. Knochel P. Angew. Chem. Int. Ed. 2006, 45: 159

Crossref PubMed Google Scholar
9 Vu VA. Marek I. Polborn K. Knochel P. Angew. Chem. Int. Ed. 2002, 41: 351

Crossref PubMed Google Scholar
10 Kopp F. Sklute G. Polborn K. Marek I. Knochel P. Org. Lett. 2005, 7: 3789

Crossref PubMed Google Scholar
11 Knochel P. Yeh MCP. Berk SC. Talbert J. J. Org. Chem. 1988, 53: 2390

Crossref Google Scholar
13 Krasovskiy A. Gavryushin A. Knochel P. Synlett 2005, 2691

Article in Thieme Connect Google Scholar
14a Negishi E. Valente LF. Kobayashi M. J. Am. Chem. Soc. 1980, 102: 3298

Google Scholar
14b Negishi E. Acc. Chem. Res. 1982, 15: 340

Google Scholar
14c Zeng X. Quian M. Hu Q. Negishi E. Angew. Chem. Int. Ed. 2004, 43: 2259

Google Scholar
15 De Lang RJ. Brandsma L. Synth. Commun. 1998, 28: 225

Crossref Google Scholar
18 Dehmlow EV. Lissel M. Heider J. Tetrahedron 1977, 33: 363

Crossref Google Scholar

12

i-PrMgCl˙LiCl is commercially available from Chemetall GmbH (Frankfurt).

16

Typical Procedure for the Preparation of trans -(2-Allylcyclopropyl)benzene (3a) and cis -(2-Allylcyclo-propyl)benzene (3b): A dry and argon-flushed 10-mL flask, equipped with a magnetic stirrer and a septum, was charged with i-PrMgCl˙LiCl (1.1 M in THF, 1.1 mmol, 1.1 equiv) and 1,4-dioxane (0.1 mL). The cis- or trans-(2-bromocyclo-propyl)benzene (1a or 1b, 197 mg, 1.0 mmol, 1.0 equiv) was added neat at 25 ˚C. The resulting mixture was stirred at 25 ˚C for 8 h to complete the Br-Mg exchange (checked by GC-MS analysis of reaction aliquots). Allyl bromide (145 mg, 1.2 mmol, 1.2 equiv) followed by CuCN˙2LiCl (1.0 M in THF, 0.01 mmol, 1.0 mol%) was added at 0 ˚C. The mixture was warmed to 25 ˚C and was quenched with a sat. aq NH₄Cl solution (10 mL). The aqueous phase was extracted with Et₂O (3 × 20 mL). The combined organic fractions were dried (MgSO₄) and after filtration the solvent was removed in vacuo. Purification by flash chromatography (pentane, silica gel) yielded 3a as a colorless oil [117 mg, 74% or 3d (117 mg, 74%)]. Spectroscopic data for 3a: ^¹H NMR (300 MHz, CDCl₃): δ = 7.09-7.32 (m, 5 H), 5.96 (ddt, J = 16.6, 10.2, 6.3 Hz, 1 H), 5.02-5.17 (m, 2 H), 2.18-2.23 (m, 2 H), 1.70-1.73 (m, 1 H), 1.12-1.23 (m, 1 H), 0.83-1.00 (m, 2 H). ^¹³C NMR (75 MHz, CDCl₃): δ = 144.0, 137.7, 128.6, 126.1, 125.7, 115.4, 38.4, 23.2, 22.8, 16.1. IR (film): 3066 (m), 3002 (m), 1640 (m), 1607 (m), 1497 (m), 1030 (w), 996 (w), 912 (s), 753 (m), 696 (vs) cm^-¹. MS (EI, 70 eV): m/z (%) = 158 (6), 118 (9), 117 (100), 116 (11), 115 (42), 104 (31), 103 (6), 91 (25), 78 (6), 77 (6). HRMS (EI, 70 eV): m/z calcd for C₁₂H₁₄: 158.1096; found: 158.1082. Spectroscopic data for 3d: ^¹H NMR (300 MHz, CDCl₃): δ = 7.21-7.33 (m, 5 H), 5.80 (ddt, J = 16.5, 10.2, 6.3 Hz, 1 H), 4.91-5.03 (m, 2 H), 2.22 (ddd, J = 8.6, 8.6, 6.1 Hz, 1 H), 1.86-1.96 (m, 1 H), 1.69 (dddt, J = 15.5, 7.8, 6.4, 1.5 Hz, 1 H), 1.15-1.27 (m, 1 H), 1.01-1.09 (m, 1 H), 0.71-0.77 (m, 1 H). ^¹³C NMR (75 MHz, CDCl₃): δ = 139.6, 138.4, 129.6, 128.2, 126.0, 114.7, 33.2, 21.4, 18.3, 9.7. IR (film): 3066 (m), 3002 (m), 2908 (w), 1640 (m), 1604 (w), 1498 (m), 1028 (w), 911 (s), 769 (m), 727 (w), 698 (vs) cm^-¹. MS (EI, 70 eV): m/z (%) = 158 (3) [M⁺], 129 (11), 128 (10), 118 (10), 117 (100), 116 (11), 115 (41), 104 (37), 103 (9), 91 (24), 78 (8), 77 (8), 65 (5), 51 (5). HRMS (EI, 70 eV): m/z calcd for C₁₂H₁₄: 158.1096; found: 158.1066.

17

Typical Procedure for the Preparation of 1-(2-Bromo-cyclopropyl)-4-fluorobenzene (1c): [¹5] [¹8] A round-bottomed flask equipped with a magnetic stirrer was charged with 1-fluoro-4-vinylbenzene (6.11 g, 50.0 mmol), CHBr₃ (50.5 g, 0.20 mol), pinacol (0.768 g, 6.50 mmol) and triethylbenzyl-ammonium chloride (0.569 g, 2.50 mmol). NaOH (8.00 g, 0.20 mol in 8 mL H₂O) was added dropwise and the reaction mixture was stirred vigorously for 16 h. Then, the solids were filtered off and washed with CH₂Cl₂ (50 mL). The aqueous layer was extracted with CH₂Cl₂ (50 mL) and the combined organic phases were dried (MgSO₄). After filtration the solvent was removed under reduced pressure and the crude product was purified by distillation (100 ˚C, 2.5 mbar), furnishing 1-(2,2-dibromocyclopropyl)-4-fluorobenzene as a colorless liquid (10.2 g, 70%). ^¹H NMR (300 MHz, CDCl₃): δ = 1.98 (t, J = 8.0 Hz, 1 H), 2.16 (dd, J = 10.5, 7.8 Hz, 1 H), 2.94 (dd, J = 10.2, 8.6 Hz, 1 H), 7.04-7.11 (m, 2 H), 7.22-7.28 (m, 2 H). ^¹³C NMR (75 MHz, CDCl₃): δ = 27.9 (CH₂), 28.5, 35.6 (CH), 115.7 (d, J = 21.6 Hz, CH), 130.9 (d, J = 8.2 Hz, CH), 132.2 (d, J = 3.1 Hz), 162.6 (d, J = 246.7 Hz, CF). IR (film): 1606 (m), 1510 (vs), 1434 (w), 1228 (s), 1220 (s), 1158 (m), 1102 (m), 1052 (m), 1038 (m), 1014 (w), 926 (w), 860 (m), 830 (vs), 818 (s), 730 (m), 676 (s), 634 (w) cm^-¹. MS (EI, 70 eV): m/z (%) = 215 (24), 213 (26), 135 (8), 134 (100), 133 (88), 107 (7), 67 (12), 57 (6). HRMS (EI, 70 eV): m/z calcd for C₉H₇ ⁷⁹Br₂F: 291.8899; found: 291.8898.
A dry and argon-flushed two-necked Schlenk flask, equipped with a magnetic stirrer and a septum was charged with LiBr (3.02 g, 34.8 mmol). The salt was dried (0.01 mbar, 5 h, 150 ˚C) and then dissolved in THF (30 mL) and Et₂O (30 mL). The solution was cooled to -80 ˚C and
n-BuLi (14.4 mL, 34.8 mmol, 2.42 M in hexane) was added, and the reaction mixture was cooled to -110 ˚C. 1-(2,2-Dibromocyclopropyl)-4-fluorobenzene (9.23 g, 31.6 mmol) was added dropwise and the reaction mixture was stirred for 1 h at -100 ˚C. Then, ethanol (15 mL) was added and the reaction mixture was warmed to 25 ˚C and was quenched with a sat. aq NH₄Cl solution (50 mL) and extracted with EtOAc (3 × 50 mL). The combined organic layers were dried (MgSO₄) and after filtration the solvent was removed under reduced pressure. Flash chromatographic purification (pentane, silica gel) furnished 1c a colorless liquid (3.37 g, 50%). ^¹H NMR (300 MHz, CDCl₃): δ = 1.37-1.55 (m, 2 H), 2.34-2.41 (m, 1 H), 2.94-2.99 (m, 1 H), 6.94-7.05 (m, 4 H). ^¹³C NMR (75 MHz, CDCl₃): δ = 18.7 (CH₂), 21.3 (CH), 26.2 (CH), 115.3 (d, J = 21.3 Hz, CH), 127.5 (d, J = 8.3 Hz, CH), 135.3 (d, J = 3.2 Hz), 161.5 (d, J = 244.3 Hz, CF). IR (film): 1608 (w), 1600 (w), 1510 (vs), 1444 (w), 1226 (vs), 1180 (w), 1160 (m), 1104 (m), 1070 (w), 1042 (w), 1014 (w), 982 (w), 934 (m), 890 (m), 860 (m), 818 (vs), 718 (m), 702 (m), 634 (w), 612 (s) cm^-¹. MS (EI, 70 eV): m/z (%) = 136 (8), 135 (100), 134 (7), 133 (26), 115 (13), 109 (14), 107 (4), 83 (4), 67 (2), 56 (3). HRMS (EI, 70 eV): m/z calcd for C₉H₈ ⁷⁹BrF: 213.9793; found: 213.9777.