1,1-Dioxobenzo[b]thiophene-2-yl methyloxycarbonyl chloride

[135204-19-2]  · C10H7ClO4S  · (MW 258.68)

(reagent for amino group protection1)

Alternate Name: benzo[b]thiophenesulfone-2-methyloxycarbonyl chloride, benzo[b]thiophenesulfone-2-methyl chloroformate, Bsmoc-Cl.

Physical Data: mp 76-77 °C.2

Solubility: soluble in all common organic solvents.

Analysis of Reagent Purity: 1H NMR, elemental analysis.

Preparative Methods: the title reagent can be prepared from benzenethiophenesulfone-2-methanol by treatment with phosgene in THF.2

Handling, Storage, and Precautions: stable in the absence of moisture, unstable toward hydrolysis on TLC plates (silica gel).

Reagent for Amino Group Protection

The Bsmoc group was recommended for protection of the a-amino function of amino acids.1,2 Such Bsmoc amino acids are useful substitutes for Fmoc amino acids for solid phase and especially rapid continuous solution syntheses of peptides. Deblocking by lower concentrations of piperidine than required for the Fmoc residue avoids base-induced side reactions. An example involves the assembly of pentapeptide 1.2

An example of Bsmoc-directed rapid solution synthesis involves the assembly of octapeptide 2.2

Selectivity in Deblocking Relative to Fm-based Protection

Due to the mechanistically distinct deblocking methodology of the Bsmoc residue (Michael-like addition) relative to that of Fmoc-based protecting groups (b-elimination), selectivity in deblocking can be achieved which represents another advantage of Bsmoc utility. Thus dipeptide 3 is exclusively Bsmoc-deblocked by means of 2% tris(2-aminoethyl)amine/dichloromethane and exclusively Fm-deblocked by means of N-methylcyclohexylamine or diisopropylamine in dichloromethane.2

Related Reagents.

9-Fluorenylmethyl chloroformate; 2-methylsulfonyl-3-phenyl-1-prop-2-enyloxycarbonyl chloride.3

1. Carpino, L. A.; Philbin, M.; Ismail, M.; Truran, G. A.; Mansour, E. M. E.; Iguchi, S.; Ionescu, D.; El-Faham, A.; Riemer, C.; Warrass, R.; Weiss, M. S., J. Am. Chem. Soc. 1997, 119, 9915.
2. Carpino, L. A.; Ismail, M.; Truran, G. A.; Mansour, E. M. E.; Iguchi, S.; Ionescu, D.; El-Faham, A.; Riemer, C.; Warrass, R. J., Org. Chem. 1999, 64, 4324.
3. Carpino, L. A.; Mansour, E. M. E., J. Org. Chem. 1999, 64, 8399.

Louis A. Carpino

University of Massachusetts, Amherst, Massachusetts, USA

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