Synthesis of Benzoate-Functionalized Phosphanes as Novel Building Blocks for the Traceless Staudinger Ligation

Abstract

A new synthetic pathway for the preparation of benzoate-functionalized phosphanes for microwave-mediated traceless Staudinger ligations is described. Novel phosphane derivatives based on 4-substituted iodophenyl benzoates were prepared via palladium(II)-catalyzed P-C cross-coupling reaction strategy in high yields. The application of microwave conditions for the ligation reactions reduced the reaction time considerably. An approach to fast and facile labeling strategies using this ligation was established.

Synthesis and Molecular Structure of 2-(Diphenylphosphano)phenyl Benzoate Borane Adduct

“…Recently, we have shown the formation of the title compound using the first synthesis way starting from acid chloride 1 and phosphanophenol 2 [4]. Here, we demonstrate the introduction of the BH3 group in the final step.…”

“…Staudinger Ligation the OH group is esterified [4,5]. To modify the appropriate acid residue it is sometimes necessary to block the phosphorus atom, especially, when working with alkylating agents which can lead to phosphonium salts or under oxidative conditions.…”

“…The first consists of the direct reaction of the borane protected phosphanophenol with acid chlorides under basic conditions and the second way involves the introduction of the BH3 group into the functionalized phosphane using BH3· THF [7]. Two crystal structures of closely related compounds resulting from such chemical reactions have been published before, see [4,5].…”

“…2-(Diphenylphosphano)phenyl benzoate (3, 150 mg, 0.39 mmol) [4] was dissolved in anhydrous THF (5 mL, Sigma Aldrich, Schnelldorf, Germany) and cooled to −78 °C. Afterwards, BH3· THF solution (1 M, 1.0 mL, 1.02 mmol, Sigma Aldrich, Schnelldorf, Germany) was added and the mixture was warmed to ambient temperature over a period of 2 h. Next, the solvent was removed and purification was done via column chromatography (petroleum ether/ethyl acetate = 10:1) to yield 4 as colorless solid (123 mg, 79%).…”

Crystal structure of N-benzyl-4-fluorobenzamide, C14H12FNO, at 173 K

“…The title compound was obtained as main product from the traceless Staudinger ligation of 2-(diphenylphosphano)phenyl-4-fluorobenzoate with benzylazide in high yield [3]. As imilar method using aflow reactor is described in [4].…”