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DOI: 10.1055/s-2002-35590
‘Safety-Catch’ Propargyl-Based Linker Strategy for the Immobilization of Amines and Carboxylic Acids in SPOS
Publication History
Publication Date:
20 November 2002 (online)
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Abstract
Integral propargyl alcohol and propargyl chloroformate linkers were developed for a ‘safety-catch’ acid-sensitive linker strategy. The syntheses of the integral propargyl linkers were achieved by direct conversion of the solid support starting from Merrifield resin, hydroxymethylpolystyrene or 4-bromopolystyrene. Amines and carboxylic acids have been coupled and released to demonstrate that transformation of the propargyl units to cobalt carbonyl complexes facilitates the cleavage under mild acidic conditions in high purity.
Key words
alkyne complexes - cobalt - linker - palladium - solid-phase
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Kusumoto S, andFukase K. inventors; Jpn. Kokai Tokkyo Koho JP 2000 186,049. ; Chem. Abstr. 2000, 133, 58365 - In the past a number of other cleavage protocols have been developed and examined in orthogonal protecting group strategies:
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19a
PPh3 (6 equiv), CCl4 (3 equiv), -20 °C, 25 min to 0 °C, 16 h, CH2Cl2, 92%;
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19b
n-BuLi (1.6 M solution in hexane, 2 equiv), -78 °C, 5 h, THF, 71%;
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19c
n-BuLi (1.6 M solution in hexane, 1.1 equiv), -78 °C to r.t., 19.5 h, THF, 74%;
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19d
DIBALH (1 M in Toluol, 2 equiv), -78 °C to r.t., 16 h, quant.
Compound 12: 1H NMR (200 MHz, CDCl3): δ [ppm] = 7.43-7.29 (m, 7 H, C-Harom.), 6.92-6.87 (m, 2 H, C-Harom.), 5.04 (s, 2 H, O-CH2), 4.46 (s, 2 H, CH2-OH), 1.78 (br s, 1 H, CH2-OH). 13C NMR (50.3 MHz, CDCl3): δ [ppm] = 158.97 (O-Carom.), 136.56 (CH2-Carom.), 133.22, 128.66, 128.14, 127.50, 114.89 (Carom.), 86.00 (CºC), 85.64 (CºC), 70.05 (CH2-OBn), 51.73 (CH2-OH); one quaternary signal of the aromatic region is overlapped by the adjacent tertiary signal. Elemental analysis: C16H14O2 (238.27 g/mol) calcd: C, 80.65; H, 5.92. Found: C, 80.58; H, 6.05. MS (FD): m/z = 238.5 (100.00), 239.5 (16.15), 240.6 (1.60). - 20 Although the solution-phase reaction
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References
All resins prepared have been characterized
by IR spectro-
scopy and by elemental analysis before and
after immobili-zation [resin 1:
nitrogen analysis (route A), bromine and nitrogen analysis (route
B); resin 2: chlorine and nitrogen analysis] as
well as Fmoc-calibration for resin 1.
The in situ deprotection protocol of Y. Fukase, K. Fukase, S. Kusumoto, [10] when applied to propargyloxycarbonyl-protected phenylalanine methylester on 1.5 mmol scale, resulted in a product mixture and unsatisfactory product purity.