Highly efficient α-C-sialylation promoted by (p-Tol)2SO/Tf2O with N-acetyl-5-N,4-O-oxazolidione protected thiosialoside as donor

Abstract

Based on a preactivation protocol with (p-Tol)2SO/Tf2O, a practical, straightforward, and high-yielding synthesis of α-sialyl C-glycosides was accomplished by coupling N-acetyl-5-N,4-O-oxazolidione protected thiosialoside with various trimethylsilyl enol ethers and allyltrimethylsilanes. High yields and excellent α-selectivities were obtained for the strong π-nucleophiles with large nucleophilicity values (N = 4.4-9.0), irrespective of whether silyl enol ethers, silyl ketene acetals or allyltrimethylsilanes were used for the electrophilic C-sialylation.

The Catalytically Lignan-Activation-Based Approach for the Synthesis of (epi)-Podophyllotoxin Derivatives

“…Again, the desired allylated EPPT 33 was isolated in a good 84% yield. Replacing 27 with the more reactive and widely accessible silyl enol ethers 28 and 29 to react with 4 led to the formation of conjugating products 34 and 36 stereoselectively (the N values of 27 and 28 are 1.8 and 6.2, respectively), paving the way for the easy accessibility of carbon-substituent-modified (E)-PPTs (82% and 100%, respectively) . Nevertheless, the stereoselectivity of the carbon-nucleophiles is highly substrate-sensitive, as exemplified by the condensation between 28 with 7 , which offered 35 as an inseparable mixture of EPPT and PPT derivatives (5:1, favoring the EPPT isomer) with a high combined yield (82%).…”

“…The 2 H 1 conformer of B favors the attack of nucleophiles from the β-face both stereoelectronically and sterically (route a vs route b ), therefore delivering the EPPT derivatives predominantly, regardless of the chirality of the starting 4- O -(2-cyclopropylethynyl)­benzoyl-( epi )-podophyllotoxin (Figure ). For carbon-type nucleophiles such as 27 – 29 , the stereoselectivity of their condensation with 4- O -(2-cyclopropylethynyl)­benzoyl-( epi )-podophyllotoxins is probably jointly controlled by both S N 1 and S N 2 reaction mechanisms. In these cases, the chirality of 4- O -(2-cyclopropylethynyl)­benzoyl-( epi )-podophyllotoxins has a profound effect on the chiral outcome of the condensations: with 4- O -(2-cyclopropylethynyl)­benzoyl-podophyllotoxin as the starting material, both S N 1 and S N 2 substitution processes give the same EPPT products, and accordingly, satisfactory stereoselectivity is obtained (for 33 , 34 , and 36 ).…”

Recent Advances in the Chemical Synthesis of C-Glycosides

“…C -Sialylation of N -acetyl-5- N ,4- O -oxazolidinone-protected thiosialoside 478 with silyl enol ethers and silyl ketene acetal under the promotion of ( p -Tol) 2 SO and Tf 2 O provided exclusively α- C -sialosides 479 – 481 in high yields (Scheme ). However, the analogous coupling with weak nucleophile allyltrimethylsilane yielded a mixture of C -sialoside 482 in 50% yield (α/β = 1:1.2). Nonetheless, with the more nucleophilic methyl-substituted allylsilane as the acceptor, the yield and stereoselectivity for the synthesis of 483 were significantly improved (80%, α only).…”

Triflic Anhydride (Tf2O)-Activated Transformations of Amides, Sulfoxides and Phosphorus Oxides via Nucleophilic Trapping

“…96 In 2013, the Xing group extended this glycosylation strategy to a C-C-bond-forming reaction for the C-sialylation of 56a using acetophenone trimethylsilyl enol ethers 56b as nucleophilic partners to generate C-sialylconjugates 56c (Scheme 56). 97 This synthetic transformation employ-ing thiosialoside 56a and silyl enol ether 56b allowed efficient access to the C-sialylconjugates 56c. Various mono-, di-, tri-, and tetra-substituted silyl enol ethers were successfully transformed into the target products 56c.…”