Formal Total Synthesis of (±)-γ-Lycorane and (±)-1-Deoxylycorine Using the [4+2]-Cycloaddition/Rearrangement Cascade of Furanyl Carbamates

Abstract

The total syntheses of gamma-lycorane and (+/-)-1-deoxylycorine were accomplished using an intramolecular Diels-Alder cycloaddition of a furanyl carbamate as the key step. The initially formed [4+2]-cycloadduct undergoes nitrogen-assisted ring opening followed by deprotonation/reprotonation of the resulting zwitterion to give a rearranged hexahydroindolinone. The stereochemical outcome of the IMDAF cycloaddition has the side arm of the tethered alkenyl group oriented syn with respect to the oxygen bridge. The key intermediate used in both syntheses corresponds to hexahydroindolinone 20. Removal of the t-Boc group in 20 followed by reaction with 6-iodobenzo[1,3]dioxole-5-carbonyl chloride afforded enamide 22. Treatment of this compound with Pd(OAc)(2) employing the Jeffrey modification of the Heck reaction provided the galanthan tetracycle 24 in good yield. Compound 24 was subsequently converted into (+/-)-gamma-lycorane using a four-step procedure to establish the cis-B,C-ring junction. A radical-based cyclization of the related enamide 33 was used for the synthesis of 1-deoxylycorine. Heating a benzene solution of 33 with AIBN and n-Bu(3)SnH at reflux gave the tetracyclic compound 38 possessing the requisite trans fusion between rings B and C in good yield. After hydrolysis and oxidation of 38 to 40, an oxidative decarboxylation reaction was used to provide the C(2)(-)C(3)(-)C(12) allylic alcohol unit characteristic of the lycorine alkaloids. The resulting enone was eventually transformed into (+/-)-1-deoxylycorine via known synthetic intermediates.

Chapter 3 Chemical and Biological Aspects of Narcissus Alkaloids

“…The resulting adduct can be elaborated into diversely substituted hydroindolinones via nitrogen-assisted ring opening (276) or Rh(II)-promoted nucleophilic reaction (277). The resulting adduct can be elaborated into diversely substituted hydroindolinones via nitrogen-assisted ring opening (276) or Rh(II)-promoted nucleophilic reaction (277).…”

Gold‐Catalyzed Cyclization of Furan‐Ynes bearing a Propargyl Carbonate Group: Intramolecular Diels–Alder Reaction with In Situ Generated Allenes

“…[2] In this regard, the intramolecular Diels-Alder reactions of furan (IMDAF), as the diene component, with av ariety of dienophiles, such as activated alkenes, alkynes,o ra llenes, [3] have been proved to be ap owerful methodology in the synthesis of polycyclic skeletons and in the total synthesis of naturalp roducts. [4] In addition,t he resulting oxygen-bridged norbornenes or norbornadienes are valuable precursors for further manipulations, [5] leadingt oawide range of functionalized molecules with biologicali nterest. [6] Generally,a llenes are more reactive than alkenes as dienophiles, however,t he utilization of allenesi nI MDAF reactions is largelyu nexplored.…”

Tandem Methodology for Heterocyclic Synthesis

“…To highlight the method, we applied the synthetic strategy to the synthesis of (±)-γ-lycorane (59) [63]. The initially formed [4+2]-cycloadduct 56 derived from furanyl carbamate 55 undergoes nitrogenassisted ring opening followed by deprotonation/reprotonation of the resulting zwitterion to give a rearranged hexahydroindolinone 57 (Scheme 15).…”