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Synlett 2003(10): 1451-1454
DOI: 10.1055/s-2003-40838
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Tuning the Reactivity of O-tert-Butyldimethylsilylimidazolyl Aminals Towards Organolithium Reagents

Thanasis Gimisis*a, Pavel Arsenyana,b, Dimitris Georganakisa, Leondios Leondiadisc
a Organic Chemistry Laboratory, Department of Chemistry, University of Athens, Panepistimiopolis, 15771 Athens, Greece
Fax: +30(210)7274761; e-Mail: gimisis@chem.uoa.gr;
b Visiting Researcher, Latvian Institute for Organic Synthesis, Aizkraukles 21, Riga, 1006, Latvia
c Mass Spectrometry and Dioxin Analysis Laboratory, IRRP, National Centre for Scientific Research ‘Demokritos’, 15310 Athens, Greece
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Publikationsverlauf

Received 26 April 2003
Publikationsdatum:
24. Juli 2003 (online)

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Abstract

O-tert-Butyldimethylsilylimidazolyl aminals are N,O-acetals that form readily from aldehydes, and although they function as aldehyde stabilizing and protecting groups under various conditions, we report here that they react with organolithium reagents similarly to the parent aldehydes. The mechanism involves the intermediate formation of a 2-imidazolyl anion as is exemplified by the isolation of 2-TBDMS-imidazole. Substitution of the imidazolyl moiety at the 2-position renders these aldehyde derivatives stable to organolithium reagents, thus allowing for the tuning of their reactivity.

Key words

aldehydes - N,O-acetals - protecting groups - organometallic reagents - Brook rearrangements

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2d: Yield: 55%, white solid, mp (MeOH/H2O): 264-265 °C. Rf (CH2Cl2/MeOH, 9:1): 0.34. 1H NMR (300 MHz, CDCl3) δ 0.07, 0.08, 0.12, 0.16 (s, 3 H each), 0.82 (s, 18 H), 1.33, 1.36 (d, 3 H each), 1.72-1.80 (m, 1 H), 2.02-2.10 (m, 1 H), 2.95 (hpt, 1 H), 4.13 (d, 1 H, J = 1.4 Hz, H-4′), 4.53 (d, 1 H, J = 4.9 Hz, H-3′), 5.74 (d, 1 H, J = 1.5 Hz, H-5′), 5.85 (dd,
1 H, J = 11.0 Hz, 4.4 Hz, H-1′), 7.14 (s, 2 H), 7.60 (s, 1 H), 7.71 (s, 1 H), 11.78 (br s, 1 H), 12.15 ppm (br s, 1 H). 13C NMR (125 MHz, CDCl3) δ -5.2, -4.8, -4.4, -4.1, 18.3, 18.6, 19.1, 19.6, 25.9, 36.7, 38.7, 70.6, 81.6, 85.6, 89.8, 115.9, 123.0, 128.8, 139.3, 139.5, 148.3, 148.7, 156.1, 180.1 ppm. IR (KBr): 2922, 1708, 1680, 1610, 1548, 840 cm-1. MS (ESI): 632.4 [M + H]+, 222.5 [B + H]+. Anal. Calcd for C29H49N7O5Si2: C, 55.12; H, 7.82; N, 15.52; Found: C, 55.30; H, 7.81; N, 15.55. 2e: Yield 50%, white solid, Rf (CH2Cl2/MeOH, 9:1): 0.38. 1H NMR (300 MHz, CDCl3) δ -0.38, -0.28, 0.07, 0.09, 0.16, 0.18 (s, 3 H each) 0.74, 0.89, 0.91 (s, 9 H each) 1.32 (s, 3 H) 1.36 (s, 3 H) 2.92-3.00 (hpt, 1 H) 4.18 (d, 1 H, H-4′) 4.32 (d, 1 H, H-3′) 4.73 (s,1 H, H-2′) 5.46 (d, 2 H, H-5′) 5.70 (s, 1 H, H-1′) 7.18 (d, 2 H) 7.58 (s, 1 H) 7.73 (s, 1 H) 11.48 (br s, 1 H) 12.25 ppm (br s, 1 H). MS (ESI): 762.6 [M + H]+, 222.5 [B + H]+. Anal. Calcd for C35H63N7O6Si3: C, 55.15; H, 8.33; N, 12.86; Found: C, 55.00; H, 8.30; N, 12.90.

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3h′: Yield 27%, white foam, Rf (CHCl3/MeOH, 9:1): 0.53. 1H NMR (500 MHz, CDCl3) δ 0.11 (s, 6 H), 0.93 (s, 9 H), 1.26 (s, 9 H), 1.29 (s, 3 H), 1.31 (s, 3 H), 2.18 (dd, 1 H, J = 13.2 Hz, 5.5 Hz), 2.71 (hpt, 1 H), 2.72-2.78 (m, 1 H), 3.37 (s, 1 H, H-5′), 4.23 (s, 1 H, H-4′), 4.54 (d, 1 H, J = 5.9 Hz, H-3′), 5.33 (br s, 1 H, OH), 6.18 (dd, 1 H, J = 9.1 Hz, 5.5 Hz, H-1′), 7.73 (s, 1 H), 8.70 (br s, 1 H), 12.05 ppm (br s, 1 H). 13C NMR (125 MHz, CDCl3) δ -4.2, -4.1, 18.4. 19.1, 19.4, 26.2, 27.0, 35.7, 36.8, 41.1, 77.0, 80.3, 88.0, 88.5, 123.4, 138.9, 147.2, 147.7, 155.5, 178.8 ppm. MS (ESI): 508.5 [M + H]+, 222.5 [B + H]+. Anal. Calcd for C24H41N5O5Si: C, 56.78; H, 8.14; N, 13.79; Found: C, 56.68; H, 8.18; N, 13.83.
3h′′: Yield 28%, white foam, Rf (CHCl3/MeOH, 9:1): 0.57. 1H NMR (500 MHz, CDCl3) δ 0.13 (s, 6 H), 0.93 (s, 9 H), 1.04 (s, 9 H), 1.26 (s, 3 H), 1.29 (s, 3 H), 2.25 (dd, 1 H, J = 13.2 Hz, 5.8 Hz), 2.70 (hpt, 1 H), 2.81-2.88 (m, 1 H), 3.57 (s, 1 H, H-5′), 4.29 (s, 1 H, H-4′), 4.76 (d, 1 H, J = 4.7 Hz, H-3′), 5.49 (br s, 1 H, OH), 6.18 (dd, H, J = 9.5 Hz, 5.9 Hz, H-1′), 7.77 (s, 1 H), 8.62 (br s, 1 H), 12.07 (br s, 1 H). 13C NMR (125 MHz, CDCl3) δ -4.3, -3.6, 18.2, 19.0, 19.3, 26.1, 27.0, 34.2, 36.8, 42.1, 73.2, 80.7, 86.3, 91.4, 123.3, 139.2, 147.2, 147.7, 155.6, 178.7 ppm. MS (ESI): 508.5 [M + H]+, 222.5 [B + H]+.

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5: Yield 82%, 1H NMR (200 MHz, CDCl3): δ 0.07 (s, 6 H), 1.25 (s, 9 H), 5.0 (br s, NH), 6.98 ppm (s, 2 H). 13C NMR (53.2 MHz, CDCl3): δ 1.0 (CH3), 25.9 (C), 30.3 (CH3), 125.5 (CH), 135.7 ppm (C).

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6b: Yield 92%, oil. Rf (CHCl3/MeOH, 98:2): 0.36. 1H NMR (200 MHz, CDCl3): δ -0.13, 0.05 [s, 3 H each, Si(CH 3)2], 0.86 [s, 9 H, SiC(CH 3)3], 2.24 (s, 3 H, CH 3), 3.72 (s, 3 H, OCH 3), 6.45 (s, 1 H, CHO), 6.79 (d, 1 H, J = 8.7 Hz, Ar-H), 6.81 (s, 1 H, Imid-H), 6.87 (s, 1 H, Imid-H), 7.09 ppm (d, 2 H, J = 8.7 Hz, Ar-H). 13C NMR (53.2 MHz, CDCl3): δ -5.0 (2 × CH3), 18.2 (C), 25.8 (3 × CH3), 36.6 (CH3), 55.5 (CH3), 80.6 (CH), 113.9 (C), 117.8 (C), 126.9 (2 × CH), 127.3 (2 × CH), 132.8 (C), 159.8 (C), 162.7 ppm (C). Anal. Calcd for C18H28N2O2Si: C, 65.02; H, 8.49; N, 8.42; Found: C, 65.22; H, 8.46; N, 8.45.
6c: Yield 84%, oil. 1H NMR (200 MHz, CDCl3): δ -0.04, 0.03 [s, 3 H each, Si(CH 3)2], 0.81 [s, 9 H, SiC(CH 3)3], 0.86 [s, 9 H, C(CH 3)3], 2.31 (s, 3 H, CH 3), 5.06 (s, 1 H, CHO), 6.80 (s, 1 H, Imid-H), 6.90 ppm (s, 1 H, Imid-H). 13C NMR (53.2 MHz, CDCl3): δ -3.4, -2.8 (each CH3), 18.2 (C), 25.4 (3 × CH3), 25.7 (3 × CH3), 31.7 (C), 36.8 (CH3), 86.4 (CH), 117.2 (CH), 121.2 (CH), 162.9 ppm (C).

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Typical Procedure: To a solution of the protected aldehyde 2a-e (0.5 mmol) in dry THF (20 mL/mmol) was added the organolithium reagent (2 equiv, Table [1] ), drop-wise, at -78 °C. After stirring for 10 min at -78 °C the temperature was let to slowly increase to 0 °C. The reaction mixture was quenched with sat aq NaHCO3 at 0 °C, diluted with ethyl acetate, the phases were separated and the organic phase was washed with water, dried over sodium sulfate, and concentrated under reduced pressure. The resulting crude 3a-h was purified by silica gel chromatography. Yields are reported in Table [1] .