Enantioselective Total Synthesis of (−)-Hamigeran F and Its Rearrangement Product

Abstract

Herein, we report the first enantioselective total synthesis of the highly complex hamigeran diterpenoid (−)-hamigeran F and its rearrangement product. The synthetic strategy features key steps of asymmetric hydrogenation, Horner−Wadsworth−Emmons olefination, and intramolecular Friedel−Crafts acylation to construct the [6,6,5]-tricyclic skeleton bearing three consecutive stereocenters, a sequence of steps involving Rosenmund reduction, Wittig reaction, dihydroxylation to assemble the α-acetoxy ketone group, and an intramolecular aldol reaction to build the tetracyclic core structure.

Marine natural products

“…449 Use of computer-assisted retro-synthetic analysis of the pupukeanane class of sesquiterpenoid MNPs identied several routes with unusual disconnections beyond those already precedented for manufacture of the compounds. 450 Diterpenoids ansellone G and hamigeran F, 451,452 eight phorbaketal congeners, 453 aromatic sterol myrmenaphthol A, and seco-sterols glaciasterol B and 6ketoaplidiasterol B have been synthesised for the rst time. 454,455 Complex tropolone-containing triterpenoid gukulenin B has also been prepared.…”

Chiral P,N,N‐Ligands for Asymmetric Hydrogenation

“…The iridium-catalyzed asymmetric hydrogenation of racemic γ,δ-unsaturated β-keto esters bearing an exocyclic double bond via DKR was developed by Xie [75] et al With the chiral spiro iridium catalyst, Ir-SpiroPAP L3, a series of exocyclic γ,δ-unsaturated βketo esters containing a five-, six-, or seven-membered ring 46 were hydrogenated to the corresponding chiral allylic alcohols 47 in high yields with good to excellent enantioselectivities (87 to > 99% ee) and cis-selectivities (93:7 to > 99:1) (Scheme 39). In addition, the asymmetric hydrogenation of racemic α-aryl-β-ethoxycarbonyl cyclopentanones via DKR for the synthesis of chiral cyclopentanols with three contiguous stereocenters was also demonstrated by Xie [76] et al This reaction was successfully used for the synthesis of natural products such as (+)-burmaniol A, (À )hamigeran B [77] and (À )-hamigeran F. [78] Interestingly, when the α,β-unsaturated β'-keto esters 48 [79] were used as substrates in the iridium-SpiroPAP L3a catalyzed asymmetric hydrogenation (Scheme 40), the C=O and C=C bonds were hydrogenated sequentially in a single step, giving the corresponding chiral cyclic alcohols 49 bearing three contiguous stereocenters with excellent enantioselec- tivities (92 to > 99% ee) and diastereoselectivities (dr 95/5 to > 99/1). The main reason for this unexpected result was that the electron-withdrawing α-ester group polarized the C=C bond, making it more susceptible to hydrogenation.…”

“…In addition, the asymmetric hydrogenation of racemic α‐aryl‐β‐ethoxycarbonyl cyclopentanones via DKR for the synthesis of chiral cyclopentanols with three contiguous stereocenters was also demonstrated by Xie [76] et al . This reaction was successfully used for the synthesis of natural products such as (+)‐burmaniol A, (−)‐hamigeran B [77] and (−)‐hamigeran F [78] …”

Highly Efficient Asymmetric Hydrogenation Catalyzed by Iridium Complexes with Tridentate Chiral Spiro Aminophosphine Ligands

“…We found that ( R )- 5e efficiently catalyzed the hydrogenation of functionalized racemic ketoesters, affording chiral cyclopentanols 37 in high yields with high enantioselectivities (up to 98% ee), cis , cis -selectivities up to >99:1, and TONs up to 10 000. This reaction was successfully used for the enantioselective synthesis of natural products such as hamigeran diterpenoids (−)-hamigeran B and (−)-hamigeran F and the phenylpropanoid (+)-burmaniol A (Figure a) …”