Enantioselective synthesis of γ-butenolides through Pd-catalysed C5-selective allylation of siloxyfurans

Pd-Catalysed asymmetric allylic alkylation of heterocycles: a user's guide

“…In contrast, the C2-substituted allyl partners preferentially led to the formation of the C5-allylated products. 94 An interesting feature of these C3 allylated butenolides is that they can be converted to the corresponding C5 allylated furanones with no erosion of the ee via a stereospecific [3,3] sigmatropic Cope rearrangement (Scheme 77C). This two-step sequence was actually exploited in the total synthesis of two members of the paraconic acid family of natural products, namely (À)-nephrosteranic acid and (À)-roccellaric acid (Scheme 77D).…”

A computational study on cobalt-catalyzed allylic substitution of racemic allylic carbonates with amines: inner-sphere C–N reductive elimination and origins of regio- and enantioselectivities

“…1–3 Among the various methods developed, the transition metal-catalyzed allylic substitution reactions have garnered significant research attention and have been widely applied in the synthesis of natural products, materials and pharmaceuticals. 2 In this context, the second- and third-row transition metal complexes, in particular those of palladium, 4 iridium, 5 and rhodium, 6 are the most commonly used transition metal catalysts for this type of transformation. On the other hand, the Earth-abundant first-row transition metals are less expensive and more environmentally friendly than their second- and third-row counterparts.…”

Convergent Total Synthesis of (−)-Cyclopamine

“…For instance, a derivative of 20 bearing a Cbz instead of a benzenesulfonyl (Bs) group was previously accessed in either nine steps 8c or six steps 8h from (S)-citronellal, with two additional steps required for protecting group exchange because the Bs group has proven to be essential for late-stage manipulations (see the SI for discussion). A concise four-step route to 20 was, thus, developed through an unusual sequence relying on the C5selective asymmetric allylic alkylation (AAA) of siloxyfuran 10, as reported by Arseniyadis et al 12 This key precedent was improved for the synthesis of γ-butenolide 17 through the addition of NH 4 OAc (as suggested by the Arseniyadis group in our correspondence), which further boosted the reaction efficiency and regioselectivity (favoring C5 allylation over C3), to deliver 17 in 75% isolated yield and 97% ee (see the SI for details). Subsequent aza-Michael addition to 17 required substantial screening (see the SI) that eventually led to the identification of BsNHOBn (N-benzenesulfonyl-O-benzylhydroxylamine) as the optimal nucleophile.…”