A three-component reagent system for rapid and mild removal of O-, N- and S-trityl protecting groups

Abstract

A new reagent system consisting of a Lewis acid such as BF3·Et2O or Cu(OTf)2, the mild protic acid hexafluoroisopropanol and the reducing quenching agent triethylsilane was elaborated for O-, N- and S-detritylation of nucleoside, carbohydrate and amino acid derivatives. The method is compatible with acetyl, silyl, acetal and Fmoc groups.

Use of Triethylsilane for Directed Enantioselective Reduction of Olefines: Synthesis of Pyrazino[2,1‐c][1,4]oxazine‐6,9‐diones with Full Control of the Absolute Configuration

“…Figure 2 depicts selected ROESY and NOESY correlations that corresponding to configurations at C 3 , C 7 and C 9 centers of representative compounds 7 SSS (1,5) and 7 RRR (2,2). In addition, NMR spectroscopic analysis of the mixture of 7 SRS/SSS (2,2) indicated that the minor diastereoisomer was structurally equivalent to compound 7 SSS (2,1), which had been synthesized from 4 SS (2,1) (see Supporting information), which thus proves the S configuration of the C 3 stereocenter. More specifically, application of the previously reported synthetic method [55] for the reaction of Fmoc-L-Ser(tBu)-OH 1 S , 2-bromo-1-(p-tolyl)ethan-1-one 2(2) and Fmoc-D-Ala-OH 3 R (2) or Fmoc-D-Ser(tBu)-OH 1 R , 2-bromo-1-(p-tolyl)ethan-1-one 2(2) and Fmoc-L-Ala-OH 3 S (1) led to very low conversions rate of intermediates 4, and acylation with Fmoc-D-Ala-OH/Fmoc-L-Ala-OH had to be repeated three times to reach quantitative conversion.…”

“…For this purpose, Fmoc-D-Ser(tBu)-OH 1 R , 2-bromo-1-(ptolyl)ethan-1-one 2(2) and Fmoc-D-Ala-OH 3 R (2) were used to synthesize intermediate 4 RR (2,2). For this purpose, Fmoc-D-Ser(tBu)-OH 1 R , 2-bromo-1-(ptolyl)ethan-1-one 2(2) and Fmoc-D-Ala-OH 3 R (2) were used to synthesize intermediate 4 RR (2,2).…”

“…The crude reaction mixture contained the desired compound in high purity and was directly subjected to TES reduction, which again, yielded a single product. For this reason, corresponding compounds 4 were obtained as a mixture of diastereomers 4 SR/SS (2,2) and 4 RS/RR (2,1). Figure 2 depicts selected ROESY and NOESY correlations that corresponding to configurations at C 3 , C 7 and C 9 centers of representative compounds 7 SSS (1,5) and 7 RRR (2,2).…”

“…Triethylsilane (TES) is a convenient, acid-promoted carbocation scavenger [1][2][3] and a mild reducing agent with broad applicability. TES is often used for reductive couplings, [4][5][6] cyclizations, [7,8] dehalogenations, [9] carbonylation, [10] alkylation of amines, [11][12][13] amides [14] and (hetero)arenes [15][16][17][18] and reductive ether/sulfide/ selenide formation.…”

“…azino [4,3-b] [1,2,5]thiadiazepinone-6,6-dioxides [48,49] and benzo-[e] [1,4]oxazino- [4,3-a] [1,4]diazepine-6,12-diones. [50] Herein, we report on an extension of the method used for the asymmetric synthesis of new hexahydropyrazino[2,1-c] [1,4]oxazine-6,9diones that allows the control of three stereocenters.…”