Stereoselective Synthesis of Superambrox: Stereoselective Type III Intramolecular Ene Reaction and OH‐Assisted Ru‐Catalyzed Isomerization

Abstract

Dedicated to Professor Georg Frµter on the occasion of his 65th birthdayIn the 1990s, chemists from Firmenich [1a] reported the isolation of (À)-1 by chemical degradation of the labdane diterpene (+)-larixol.[1b] This unsaturated analogue of Ambrox [2] was named "Superambrox" as a result of its excellent odor qualities (Scheme 1).To our knowledge, the only synthetic approaches towards Superambrox are based on acid-mediated polyene cyclizations, [3] which afford the racemate with low stereoselectivity in only moderate yields. We now report a concise, highly selective synthesis of racemic Superambrox (AE )-1. The creation of the CÀC double bond in a highly substituted environment presents a special challenge, as this subunit is known to be prone to isomerization or skeletal rearrangement. A second difficulty lies in the stereoselective elaboration of the heterocycle.Our synthetic plan consists of the development of a new tandem type III intramolecular ene reaction/Oppenauer oxidation of dihydro-b-C14-aldehyde (2), a high-tonnage raw material, thus allowing a direct approach to the decalone 3, which has the properly positioned double bond. Acetoxylation from the less-hindered a face followed by intra-

Improved Catalysts for the Iridium‐Catalyzed Asymmetric Isomerization of Primary Allylic Alcohols Based on Charton Analysis

“…The catalyst displayed interesting TON for substrates having a mono‐ or disubstituted double bond, but was ineffective for allylic alcohols with higher substitution patterns (i.e., potential prochiral substrates). More recently, Fehr and Farris observed that Crabtree’s hydrogenation catalyst C (Figure 1) promoted an exclusive isomerization/lactolization sequence rather than the initially expected hydrogenation, even though a hydrogen atmosphere was maintained 8. 9 The observation by Baudry and Ephritikhine that C was also competent at promoting the isomerization of allylic alcohols, albeit with reproducibility issues, suggested the isomerization/lactolization sequence discovered by Fehr and Farris may be very substrate specific.…”

Catalytic Activation of Olefins by Metal Triflates and Triflimides: Application to Fragrance Chemistry

“…In the presence of a stoichiometric amount of EtAlCl 2 as the Lewis acid, only the ene-reaction occurs (Scheme 7). [36] The tricyclic ether 9 has notes of cedar, rotted wood and perspiration.…”

trans‐Tetrahydrofurans by OH‐Assisted Ru‐Catalyzed Isomerization of 2‐Butene‐1,4‐diols

“…Recently, we described a stereoselective synthesis of rac ‐Superambrox ( 1 ) 1. The trans configuration of the tetrahydrofuran ring was obtained by an unprecedented, highly selective OH‐assisted Ir‐ or Ru‐catalyzed isomerization of diol 3 and subsequent reduction of lactol 4 by using Et 3 SiH2 (Scheme ).…”