Et₃B-mediated two- and three-component coupling reactions via radical decarbonylation of α-alkoxyacyl tellurides: single-step construction of densely oxygenated carboskeletons

Abstract

We devised new radical-based two- and three-component coupling reactions of sugar derivatives, and realized one-step construction of contiguously substituted polyol structures.

Et3B/Et2AlCl/O2‐Mediated Radical Coupling Reaction between α‐Alkoxyacyl Tellurides and 2‐Hydroxybenzaldehyde Derivatives

“…Next, to explore the scope of the radical coupling reactions, the optimized conditions were applied to four α‐alkoxyacyl tellurides 1 b – 1 e (Table 2). Acyl tellurides 1 b , 1 c / d , and 1 e were easily prepared from d ‐fructose, d ‐ribose, and d ‐tartaric acid derivatives, respectively [4,7a,b] . Upon treatment with 2‐hydroxybenzaldehyde ( 7 a , 3 equiv) in the presence of Et 3 B (5 equiv) and Et 2 AlCl (3 equiv) in CH 2 Cl 2 under air at 25 °C, the radical precursors 1 b – 1 e were transformed into the corresponding α‐alkoxy radicals, which reacted with aldehyde 7 a to afford 8 b – 8 e in 57% to 94% yields.…”

Unified Total Synthesis of Polyoxins J, L, and Fluorinated Analogues on the Basis of Decarbonylative Radical Coupling Reactions

“…2:1a tC5). [11,12] Thec ompatibility of the preinstalled nucleobases with the reaction conditions was unknown at this stage, [13,14] but we expected that direct attachment of the a-amino acid portion to 5a-d would streamline the route to 1a-d.…”

“…Ther adical-exchange reaction between 5a-d/6 and the ethyl radical generated from Et 3 Band O 2 provides the corresponding a-alkoxyacyl radical Aa-d/C.N ext, favorable orbital interactions of the C À CO s*-bond of Aa-d/C with the antiperiplanar oxygen lone pair facilitates ejection of CO to generate Ba-d/D. [11,12,22] Thel ost stereochemical information at the C4' or C3'' position of Ba-d/D is redefined by CÀC bond formation. Thea cetonide methyl group of the 5/5-cisfused bicycle Ba-d,and the siloxymethyl group of monocycle D,block the corresponding top and bottom faces,respectively, thus forcing the approach of oxime 4 from the opposite faces to establish the C4' and C3'' stereocenters.…”

Unified Total Synthesis of Polyoxins J, L, and Fluorinated Analogues on the Basis of Decarbonylative Radical Coupling Reactions

“…To simplify the synthetic scheme and minimize functional-group transformations,w e decided to extend the multiply functionalized chains of 1a-d from readily accessible ribonucleosides 5a-d containing four different nonprotected pyrimidine rings. [11,12] Thec ompatibility of the preinstalled nucleobases with the reaction conditions was unknown at this stage, [13,14] but we expected that direct attachment of the a-amino acid portion to 5a-d would streamline the route to 1a-d. [10] We recently reported that a-alkoxyacyl telluride 7 and oxime 8 were smoothly assembled into the ribonofuranosyl a-amino acid 9 through Et 3 B/O 2 -promoted decarbonylative radical addition, albeit with low C5 stereoselectivity (d.r.…”

“…[20] Despite the differences in the C5 substituents on the pyrimidine rings,E t 3 B/O 2 -promoted reactions of 5b, 5c, and 5d successfully attached the a-amino acid structure to yield 2b (64 %), 2c (69 %), and 2d (64 %) in ad iastereoselective fashion with respect to the formation of the C4' and C5' centers.T he same procedure was applied to 6 and 4 (2 equiv) to produce the protected trihydroxynorvaline fragment 3 with complete control of the newly formed C2'',C3'' stereocenters.T hus, 2a-d and 3 were prepared in only four steps from the starting materials 10 a-d and 12,respectively. [11,12,22] Thel ost stereochemical information at the C4' or C3'' position of Ba-d/D is redefined by CÀC bond formation. Ther adical-exchange reaction between 5a-d/6 and the ethyl radical generated from Et 3 Band O 2 provides the corresponding a-alkoxyacyl radical Aa-d/C.N ext, favorable orbital interactions of the C À CO s*-bond of Aa-d/C with the antiperiplanar oxygen lone pair facilitates ejection of CO to generate Ba-d/D.…”