Chemistry of 1-Alkoxy-1-glycosyl Radicals:  The Manno- and Rhamnopyranosyl Series. Inversion of α- to β-Pyranosides and the Fragmentation of Anomeric Radicals

Abstract

The formation and stereoselective quenching of 1-mannopyranosyl radicals by a tributyltin hydride-mediated intramolecular 1,5-hydrogen abstraction sequence is described. A competing process is 1,4-hydrogen atom abstraction leading principally to glucopyran-2-ulosides. Fragmentation of the anomeric radical resulting in the formation of ring opened products is a problem in certain series. The chemistry is dictated to a considerable extent by the nature of the protecting groups employed with the 4,6-benzylidene series and, for rhamnose, the Ley 3,4-dispiroketal, being particularly susceptible to the 1,4-hydrogen atom abstraction but less to the fragmentation. Photochemical conditions are described, in which these side reactions are practically eliminated, and applied to the inversion of an alpha- to a beta-mannoside in a disaccharide.

CHEMISTRY OF GLYCOSYL TRIFLATES: SYNTHESIS OFβ-MANNOPYRANOSIDES

“…Jarmila Brunckova thus prepared S-ethyl 4,6-benzylidene-a-Dthiomannopyranoside by standard means and converted it to the 3-O-benzyl-2-O-tertbutyldimethylsilyl derivative (14) by the aegis of dibutyltin oxide and benzyl bromide, then TBDMS triflate. [21] Brunckova noted the highly selective sulfoxidation process, which gave essentially a single diastereomer, in contrast to the unselective oxidations bthioglycosides observed previously, [23] but was unable to assign configuration at the time. [21] Brunckova noted the highly selective sulfoxidation process, which gave essentially a single diastereomer, in contrast to the unselective oxidations bthioglycosides observed previously, [23] but was unable to assign configuration at the time.…”

“…In fact it was several years before Jan Mataka and Sanxing Sun were able to prepare crystalline derivatives suitable for X-ray analysis and so assign the configuration as S R . [21] The TBDMS protecting group was removed and was replaced by the radical precursor, and the radical inversion procedure was conducted with moderate success, comparable to that seen with the a-methyl mannoside. In line with our expectations, a good yield of a 10:1 mixture of glycosides (17) favoring the a anomer was obtained (Scheme 6).…”

“…[25] Brunckova then mixed the sulfoxide with methyl 2,3,4-tri-Oacetyl-a-D-glucopyranoside (16) and 2,6-di-tert-butyl-4-methylpyridine (DTBMP), a hindered base, in diethyl ether at À 78°C and activated the sulfoxide by dropwise addition of triflic anhydride. [21] Sanxing Sun, a new student, sought to prepare more of the a-disaccharide (17) and subsequently to improve the radical inversion process. [21] The TBDMS protecting group was removed and was replaced by the radical precursor, and the radical inversion procedure was conducted with moderate success, comparable to that seen with the a-methyl mannoside.…”

Mechanistic Investigations into the Application of Sulfoxides in Carbohydrate Synthesis

“…While pursuing a radical‐based solution to the ubiquitous problem of stereoselective β‐mannopyranoside synthesis, Crich and co‐workers serendipitously uncovered an unappreciated level of complexity in Kahne's sulfoxide glycosylation method . When using benzylidene acetal protected donor 8 , Crich observed that the stereoselectivity of the reaction was dependent on the order of addition of the acceptor and activating agent (Scheme ).…”

Regioselective Benzoylation of 6‐O‐Protected and 4,6‐O‐Diprotected Hexopyranosides as Promoted by Chiral and Achiral Ditertiary 1,2‐Diamines

“…Benzoylation of the b-d-mannopyranoside 47 gave mostly the 3-benzoate 48 [65], isolated in 90% yield ((S)-1) or 62.5% ((R)-1). Benzoylation of the a-d-mannopyranoside 49 was less strongly influenced by the catalysts than that of 27, providing 85, 62, and 74% of the 3-benzoate 51 [55] as the major product in the presence of (S)-1, (R)-1, and TMEDA, respectively.…”