A Conia‐Ene‐Type Cyclization under Basic Conditions Enables an Efficient Synthesis of (−)‐Lycoposerramine R

Abstract

An enantioselective total synthesis of the Lycopodium alkaloid lycoposerramine R is presented. It relies on a base-mediated cyclization that resembles the Conia-ene reaction of ynones and gold-catalyzed variants thereof. Thus, hydrindanones and other functionalized ring systems bearing an exocyclic alkene can be rapidly accessed at room temperature without noble metal catalysis or substrate preactivation.

Progress towards the Total Syntheses of Lycopodium Alkaloid, Lycopladine A

“…The failure of direct C-5 allylic oxidation of 63 led to investigate a longer route by the aid of hydroboration-oxidation series. [42] However, utilising organoboranes like Cy 2 BH, Sia 2 BH, 9-BBN, BH 3 · SMe 2 and BH 3 · THF and also catecholborane or pinacolborane with Wilkinson's catalyst; with oxidants NaOH/H 2 O 2 or sodium perborate furnished low yields. Ultimately, hydroboration-oxidation of 63 was efficiently achieved with significant yield by employing {[Ir(cod)Cl] 2 /dppe} coupled with pinacolborane; wherein, alcohol 64 was obtained after oxidative workup.…”

Synthesis of cis-hydrindan-2,4-diones bearing an all-carbon quaternary center by a Danheiser annulation

“…Almost all the strategies developed to date involve the formation of the C3–C3a bond in the ring-closing step leading to the hydrindane nucleus. The carbocyclization takes place from polyfunctionalized cyclohexanones or related compounds through a Michael reaction [ 7 ], successive inter- and intramolecular radical processes [ 8 ], intramolecular carbene addition/cyclization [ 9 – 10 ], aldol cyclizations either under Lewis acid catalysis [ 11 ] or from diazoketones in the presence of bases (e.g., DBU) [ 12 ], Pd-catalyzed cycloalkenylation of a silyl enol ether [ 13 ], or base-promoted ynone carbocyclizations [ 14 – 15 ]. Another approach through an aldol cyclization, forming the C1–C7a bond instead, has also been reported [ 16 ].…”

“…Thus, we surmised that building block 1 could be a new precursor of 3a-substituted hydrindan-2,4-diones ( Scheme 1 ). This type of compounds, when adequately functionalized, has been used as advanced intermediates for the synthesis of the Lycopodium alkaloids carinatine A [ 11 , 14 – 15 ], 8-deoxyserratinine [ 10 ], fawcettidine [ 10 ], fawcettimine [ 7 , 10 ], lycojaponicumin C [ 10 ], lycopladine A [ 11 , 13 – 15 ], lycoposerramine R [ 13 – 14 ], and sieboldine [ 19 – 20 ] ( Fig. 2 ).…”

Pd-catalyzed asymmetric allylic substitution cascade using α-(pyridin-1-yl)-acetamides formedin situas nucleophiles

“…Quaternary pyridinium salts A (Fig. 1), generally used as activated pyridines, are very attractive synthons for synthetic chemists because of their ease of preparation and unique reactivity 5–8. They have received significant interest for use in many types of transformation, for example, Michael additions,5 a 1,3-dipole additions,5 b Kröhnke reaction,5 c etc.…”

“…From the viewpoint of functionalization, A can roughly be divided into three activated types: ketones A1 ,6 esters A2 7 and amides A3 (Fig. 1),8 which have been applied in the synthesis of anti-mycobacterial compounds,6 a NF-κB inhibitors7 a and 5-HT2c modulators,8 a respectively. The main method to prepare these heterocyclic compounds is via functionalization of the α-positions of A1 , A2 and A3 .…”