Stereocontrolled (Me₃Si)₃SiH-Mediated Radical and Ionic Hydride Transfer in Synthesis of 2,3,5-Trisubstituted THF

Abstract

2,3,5-Trisubstituted tetrahydrofurans were prepared stereoselectively through a two-step process involving the addition of an acyl radical to a β-silyloxy acrylic ester followed by an acid-catalyzed desilylation-ketalization sequence and a final oxocarbenium reduction step. High levels of 1,2- and 1,3-stereocontrol were attained when (Me3Si)3SiH was used as a radical followed by a ionic hydrogen transfer agent.

Acyl Radical Addition to Activated Olefins: A Stereocontrolled Route to Polysubstituted Tetrahydrofurans and Lactones, and Application to the Total Synthesis of (+)‐No. 2106 A

“…The latter was prepared in good yield with a moderate 4:1 diastereoselectivity, through the addition of acrylate ester 5 to aldehyde 6 . In contrast with earlier observations made on substrates bearing a silyl‐protected alcohol, the radical reaction carried out on free allylic alcohol 7 under the reported conditions [TTMSH, t BuON=NO t Bu (DTBHN) in benzene] led to no reaction. When the reaction was repeated with the addition of Et 2 BOMe (1 equiv.…”

“…A tentative rationalization of the selectivity may be carried out, invoking a conformation such as A at the transition state (Scheme ) , , . In this conformation, the silane approaches from the top face to minimize A 1,3 ‐strain.…”

“…A new strategy was thus developed involving the sequential formation of the C‐4–C‐5 then C‐5–O bonds of the THF. A diastereocontrolled addition of a nucleophilic acyl radical to an acrylic ester was followed by a cyclization to form a hemiketal, which was finally reduced by a hydride source . We showed that hydrogen transfer during both the radical addition and the hemiacetal reduction was efficiently carried out by (Me 3 Si) 3 SiH (TTMSH) in good yields and with high levels of stereocontrol.…”

Acyl Radical Addition onto Aza‐Baylis–Hillman Adducts: A Stereocontrolled Access to 2,3,5‐Trisubstituted Pyrrolidines

“…In the latter, a putative hydrogen bonding between the furyl oxygen and the tosylamide N–H, would lead the hydrogen to eclipse the enoyl system as in A 1,3 models, the two diastereotopic faces being weakly differentiated . 1,3‐Stereocontrol may be explained as proposed earlier in the tetrahydrofuran series . Reduction of the iminium likely proceeds through an envelope conformation such as B (Figure ), with the ester group in a pseudo‐axial position so as to maximize electrostatic effects with the iminium ions .…”

A Cascade of Prins Reaction and Pinacol‐Type Rearrangement: Access to 2,3‐Dideoxy‐3C‐Formyl β‐C‐Aryl/Alkyl Furanosides and 2‐Deoxy‐2C‐Branched β‐C‐Aryl Furanoside

“…Further, synthesis and study of non‐natural C ‐aryl furanosides and their comparison with C ‐nucleosides is also an important area of research to study and for probing them as nucleobases. Thus, owing to their fascinating structural features and inherent biological properties, construction of tri and tetra substituted β‐ C ‐aryl/alkyl furanosides in a highly stereoselective manner is a significantly challenging task in synthetic carbohydrate chemistry.…”