Diastereoselective Friedel-Crafts Alkylation Reactions Employing Chiral Cation Precursors with Polar α-Substituents

Daniel Stadler; Friedrich Mühlthau; Philipp Rubenbauer; Eberhardt Herdtweck; Thorsten Bach

doi:10.1055/s-2006-951471

LETTER

Diastereoselective Friedel-Crafts Alkylation Reactions Employing Chiral Cation Precursors with Polar α-Substituents

Daniel Stadler^a, Friedrich Mühlthau^a, Philipp Rubenbauer^a, Eberhardt Herdtweck^b, Thorsten Bach*^a
^a Lehrstuhl für Organische Chemie I, Technische Universität München, Lichtenbergstr. 4, 85747 Garching, Germany
Fax: +49(89)28913315; e-Mail: thorsten.bach@ch.tum.de;
^b Lehrstuhl für Anorganische Chemie, Technische Universität München, Lichtenbergstr. 4, 85747 Garching, Germany
Fax: +49(89)28913473; e-Mail: eberhardt.herdtweck@ch.tum.de;

Abstract

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Abstract

Precursors 5-7 of chiral para-methoxybenzyl cations (2-4), which carry a polar substituent (NO₂, CN, OH) at the stereogenic α-carbon atom, reacted under acidic conditions with high facial diastereoselectivity (dr = 75:25 to >95:5) to the corresponding 1,1-diarylalkanes threo-9 (50-87% yield). Catalytic amounts of Sc(OTf)₃ as Lewis acid were sufficient to convert epoxide 7 into the corresponding alcohols threo-9ca and threo-9cb.

Key words

carbocations - stereoselective synthesis - electrophilic aromatic substitutions - alkylations - diastereoselectivity

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Referenzen

References and Notes

To whom inquiries regarding the X-ray crystallographic data should be directed.

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<A NAME="RG17706ST-2B">2b</A> Olah GA. Friedel-Crafts Chemistry John Wiley & Sons; New York: 1973.

<A NAME="RG17706ST-2C">2c</A> Friedel-Crafts and Related Reactions Vol. 2: Olah GA. Interscience Publishers; New York: 1963.

<A NAME="RG17706ST-3A">3a</A> Price CC. Lund M. J. Am. Chem. Soc. 1940, 62: 3105

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<A NAME="RG17706ST-5">5</A> For an early example possibly involving cations related to 2, see: Hodge EB. J. Am. Chem. Soc. 1951, 73: 2341

Alcohol 5:

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<A NAME="RG17706ST-6B">6b</A> Dumez E. Faure R. Dulcère J.-P. Eur. J. Org. Chem. 2001, 2557

Alcohol 6:

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Representative Procedure: 1-(4-Methoxyphenyl)-2-nitropropane-1-ol (5; 106 mg, 0.50 mmol) was placed in a flame-dried flask, dissolved in anhyd CH₂Cl₂ (10 mL) and cooled to -78 °C. After addition of HBF₄·OEt₂ (86.0 µL, 102 mg, 0.63 mmol) and stirring for 5 min, N-tosylpyrrole (8c; 443 mg, 2.00 mmol) was added and the solution was allowed to warm to r.t. over a period of 15 min. Then the reaction was stopped by adding sat. aq NaHCO₃ solution (20 mL), the mixture was diluted with Et₂O (20 mL) and the separated organic layer was washed with sat. aq NaHCO₃ (20 mL) and sat. aq NaCl solution (20 mL). After drying with Na₂SO₄, it was filtered and the solvent was evaporated under reduced pressure. Column chromatography (pentane-Et₂O, 9:1) yielded the product 9ac (162 mg, 0.39 mmol, 78%) in a diastereomeric ratio of threo/erythro >95:5. R _f 0.10 (pentane-Et₂O, 8:2). ¹H NMR (360 MHz, CDCl₃): δ = 1.38 (d, ³ J = 6.6 Hz, 3 H), 2.35 (s, 3 H), 3.77 (s, 3 H), 4.95 (dq, ³ J = 11.3 Hz, ³ J = 6.6 Hz, 1 H), 5.10 (d, ³ J = 11.3 Hz, 1 H), 6.24 (t, ³ J = 3.4 Hz, 1 H), 6.41-6.46 (m, 1 H), 6.76 (d, ³ J = 8.6 Hz, 2 H), 7.08 (d, ³ J = 8.6 Hz, 2 H), 7.14 (d, ³ J = 8.2 Hz, 2 H), 7.20 (dd, ³ J = 3.4 Hz, ⁴ J = 1.6 Hz, 1 H), 7.40 (d, ³ J = 8.2 Hz, 2 H). ¹³C NMR (90.6 MHz, CDCl₃): δ = 19.5 (q), 21.7 (q), 46.8 (d), 55.4 (q), 86.5 (d), 111.8 (d), 112.0 (d), 114.1 (d), 124.0 (d), 126.7 (d), 129.0 (s), 129.8 (d), 130.3 (d), 133.8 (s), 136.3 (s), 144.7 (s), 159.3 (s). Anal. Calcd for C₂₁H₂₂N₂O₅S (414.5): C, 60.85; H, 5.35; N, 6.76; S, 7.74. Found: C, 60.77; H, 5.20; N, 6.74; S, 7.65.

Representative Procedure: 2-(4-Methoxyphenyl)-3-methyloxirane (7; 82.1 mg, 0.50 mmol) was placed in a flame-dried flask, dissolved in anhyd CH₂Cl₂ (10 mL) and cooled to -78 °C. After addition of 2-methylthiophene (8a; 0.19 mL, 196 mg, 2.00 mmol) and BF₃·OEt₂ (79.2 µL, 88.7 mg, 0.63 mmol) the solution was stirred for 30 min at -78 °C and for 1 h at r.t. Identical workup as in the previous procedure⁹ and column chromatography (pentane-Et₂O, 7:3) yielded the product 9ca (114 mg, 0.44 mmol, 87%) in a diastereomeric ratio of threo/erythro = 88:12. Data for the major diastereoisomer: R _f 0.18 (pentane-Et₂O, 7:3). ¹H NMR (360 MHz, CDCl₃): δ = 1.15 (d, ³ J = 6.1 Hz, 3 H), 1.92 (s, 1 H), 2.42 (d, ⁴ J = 1.0 Hz, 3 H), 3.78 (s, 3 H), 3.92 (d, ³ J = 8.2 Hz, 1 H), 4.28 (qd, ³ J = 6.1 Hz, ³ J = 8.2 Hz, 1 H), 6.59-6.60 (m, 1 H), 6.77 (d, ³ J = 3.4 Hz, 1 H), 6.85 (d, ³ J = 8.7 Hz, 2 H), 7.22 (d, ³ J = 8.7 Hz, 2 H). ¹³C NMR (90.6 MHz, CDCl₃): δ = 15.2 (q), 21.1 (q), 55.2 (d), 55.3 (q), 71.2 (d), 114.0 (d), 124.7 (d), 125.2 (d), 129.0 (d), 134.2 (s), 139.0 (s), 142.7 (s), 158.4 (s). Anal. Calcd for C₁₅H₁₈O₂S (262.4): C, 68.67; H, 6.92. Found: C, 68.63; H, 6.92.

<A NAME="RG17706ST-11">11</A> Examples for stereoconvergent reactions include the reaction 5 → 9aa, in which the starting material 5 was used in varying anti/syn ratios (62:38 to 86:14) yielding product 9aa with identical selectivity (dr = 91:9), and the BF₃-promoted reaction 7 → 9ca, in which the trans/cis ratio of the epoxide 7 varied from <5:95 to >95:5 while the product selectivity (dr = 88:12) remained constant

Crystal data for 9ac: C₂₁H₂₂N₂O₅S, M_r = 414.48, orthorhombic, space group Pna2₁, Final R indices [I > 2σ (I)], R1 = 0.0241, (all data) wR2 = 0.0613, a = 13.8819 (2) Å, b = 7.5952 (1) Å, c = 18.9277 (2) Å, V = 1994.95 (4) Å³, T = 123 K, Z = 4, reflections collected/unique: 49268/3432 (R _int = 0.038), number of observations [>2σ (I)] 3296, parameters 351. Crystallographic data (excluding structure factors) for 9ac have been deposited with the Cambridge Crystallographic Data Centre as supplementary publication no. CCDC-604901.

Crystal data for the nitrobenzoate of 9ca: C₂₂H₂₀N₂O₇S, M_r = 456.47, orthorhombic, space group Pna2₁, Final R indices [I > 2σ(I)], R1 = 0.0353, (all data) wR2 = 0.0873, a = 34.8337 (3) Å, b = 5.5220 (1) Å, c = 21.9007 (2) Å, V = 4212.64 (9) Å³, T = 173 K, Z = 8, reflections collected/unique: 764938/7730 (R _int = 0.053), number of observations [>2σ (I)] 6128, parameters 584. Crystallographic data (excluding structure factors) for 9ca have been deposited with the Cambridge Crystallographic Data Centre as supplementary publication no. CCDC-604902.

The sequence included

reduction to the aldehyde [DIBAL-H, -78 °C → r.t. (THF), 69%]

oxidation to the free acid [NaClO₂, 2-methylbutene, 0 °C → r.t. (t-BuOH-H₂O), 76%], and

intramolecular Friedel-Crafts acylation [i) (COCl)₂, r.t. (CH₂Cl₂), ii) AlCl₃, 130 °C (PhCl), 53% (two steps)].

<A NAME="RG17706ST-15">15</A> Iwasawa N. Matsuo T. Iwamoto M. Ikeno T. J. Am. Chem. Soc. 1998, 120: 3903

<A NAME="RG17706ST-16">16</A> Eliel EL. Wilen SH. Stereochemistry of Organic Compounds John Wiley & Sons; New York: 1994.

Strictly speaking, the corresponding OBF₃-substituted carbenium ion must be considered instead of 4 (X = OH) but it is known that the steric demand of an OR group is not heavily dependent on the R group.¹⁶ Indeed, the diastereoselectivity does not differ much for either catalyst HBF₄·OEt₂ or BF₃·OEt₂ (entries 7 and 8 in Table [1] ).

<A NAME="RG17706ST-18">18</A> Hoffmann RW. Chem. Rev. 1989, 89: 1841

FeCl₃:

<A NAME="RG17706ST-19A">19a</A> Review: Iovel I. Mertins K. Kischel J. Zapf A. Beller M. Angew. Chem. Int. Ed. 2005, 44: 3913

<A NAME="RG17706ST-19B">19b</A> Kischel J. Jovel I. Mertins K. Zapf A. Beller M. Org. Lett. 2006, 8: 19

Sc(OTf)₃:

<A NAME="RG17706ST-19C">19c</A> Tsuchimoto T. Tobita K. Hiyama T. Fukuzawa S. J. Org. Chem. 1997, 62: 6997

<A NAME="RG17706ST-19D">19d</A> Noji M. Ohno T. Fuji K. Futaba N. Tajima H. Ishii K. J. Org. Chem. 2003, 68: 9340

<A NAME="RG17706ST-19E">19e</A> B(C₆F₅)₃: Rubin M. Gevorgyan V. Org. Lett. 2001, 3: 2705

Representative Procedure: 2-(4-Methoxyphenyl)-3-methyloxirane (7; 82.1 mg, 0.50 mmol) was placed in a flame-dried flask, dissolved in nitromethane (5 mL) at ambient temperature. After addition of 2-methylthiophene (8a; 0.19 mL, 196 mg, 2.00 mmol) and Sc(OTf)₃ (2.5 mg, 5 µmol) the solution was stirred for 21 h. Identical workup as in the previous procedure⁹ and column chromatography (pentane-Et₂O, 7:3) yielded the product 9ca (88.0 mg, 0.34 mmol, 67%) in a diastereomeric ratio of threo/erythro 87:13.