Ligand‐Controlled Stereoselective Synthesis of 2‐Deoxy‐β‐C‐glycosides by Cobalt Catalysis

Abstract

2-Deoxy-β-C-glycosides represent an important class of carbohydrates that are present in many bioactive molecules. However, owing to the lack of substituents at the C2 position, the stereoselective synthesis of 2-deoxy-β-C-glycosides is highly challenging. Herein, we report a ligand-controlled stereoselective Calkyl glycosylation reaction to access 2-deoxy-β-C-alkyl glycosides from readily available glycals and alkyl halides. This method exhibits broad substrate scope and excellent diastereoselectivity under very mild conditions. In addition, unprecedented stereodivergent synthesis of 2-deoxy-C-ribofuranosides is achieved using different chiral bisoxazoline ligands. Mechanistic studies suggest that hydrometallation of the glycal with the bisoxazoline-ligated CoÀ H species may be the turnover-limiting and stereodetermining step of this transformation.

Ligand-Controlled Cobalt-Catalyzed Regio-, Enantio-, and Diastereoselective Oxyheterocyclic Alkene Hydroalkylation

“…7 However, without exception, auxiliary groups are required to attain high regio-and enantioselectivities. Activated alkyl electro-philes with a conjugated group 8 or alkenes with a chelationdirecting group 9 are suitable substrates in enantioselective alkene hydroalkylation (Figure 1B). Notably, our group achieved the enantioselective hydroalkylation of monofluoroalkenes in the absence of a chelation-directing group, however, still constrained to activated alkenes with a conjugated functional group.…”

Nickel-Catalyzed Remote Asymmetric Hydroalkylation of Alkenyl Ethers to Access Ethers of Chiral Dialkyl Carbinols

“…Continuing our interest in hydroalkylation reactions, ,,,,, we sought to conduct a rational ligand modification with the designs and realize the synchronous implementation of alkene isomerization and asymmetric hydroalkylation (Figure C). Herein, we report a nickel-catalyzed remote asymmetric hydroalkylation of alkenyl ethers.…”

Application of Redox-Active Ester Catalysis to the Synthesis of Pyranose Alkyl C-Glycosides

“…A broader implementation of this methylene replacement strategy remains challenging, however, given the lack of flexible and direct methods for forming anomeric sp 3 –sp 3 exo -C linkages. While there have been significant advances in acyl and aryl C-glycosylation by several groups (Scheme ), − catalytic sp 3 –sp 3 alkyl coupling at the pyranose anomeric center is still an emerging field, − and direct coupling methods often require the use of unstable glycosyl halides (Scheme b,c). − In search of a more practical alkyl exo -C-glycosylation strategy, we were drawn to the work of the Baran lab (Scheme d), which showed shelf-stable N -hydroxyphthalimide (NHPI) esters could be activated by Ni catalysis to forge sp 3 –sp 3 linkages as a higher-yielding alternative to Barton decarboxylation. − With this precedent in mind, we proposed that a similar coupling of shelf-stable anomeric tetrachloro- N -hydroxyphthalimide (TCNHPI) ester donors and dialkylzinc acceptors could yield pyranose alkyl C -glycosides in a light-free, decarboxylative Negishi-type process (Scheme e). Notably, through the use of α-alkoxy furan-containing organozincs, we also envisioned it would be possible to access exo -C-linked disaccharides via an Achmatowicz rearrangement, , as shown in our group’s prior work with homoacyl furanyl C -glycosides …”