Transannulation Reactions in the Synthesis of Natural Products

Abstract

An overview on the construction of polycyclic natural products by use of transannulation reactions across medium and large rings is presented.

A Two‐Component Alkyne Metathesis Catalyst System with an Improved Substrate Scope and Functional Group Tolerance: Development and Applications to Natural Product Synthesis

“…[65] ii)I ti sd ifficult to predict if the transannular contexto ft he envisaged Michael addition cascade imposes additional constraints. [66] iii)W ea re unaware of any precedenti nw hich two redox isomerizations were carried out concomitantly (see J!I); [67,68] with severalh eteroelements and nucleophilic C-atoms present within the congested framework of as ubstrate of type J,manys ide tracks are conceivable. iv) For the macrocyclic frame in J to be forged, two out of three tripleb onds in the cyclization precursor K have to participate in metathesis while the third one has to pass untouched;a lthough this type of selectivity is unprecedented, we presumed that ab ulky protecting group Ro n the propargyl alcohola tC 3m ight turn the adjacent C1À C2 triple bond into an innocent by-stander during RCAM.…”

Total Synthesis of (−)‐Merochlorin A

“…While transannular cyclizations have been found to occur with high stereoselectivity and efficiency within macrocyclic settings, [29] smaller ring sizes,a nd especially bridged systems, can suffer from low reactivity owing to high strain energies. Oxidation of the primary alcohol (19)t ot he corresponding aldehyde or ester and treatment with standard aldol reaction conditions (such as K 2 CO 3 ,M eOH or aq.…”

Nickel‐Catalyzed Chemo‐, Regio‐ and Diastereoselective Bond Formation through Proximal CC Cleavage of Benzocyclobutenones

“…[18] Such argument goes in line with the observation that 3e-3g were obtained as mixtures of regioisomers with as light preference for C5 selectivity. [23] In light of these results,w ew ondered whether our Nicatalyzed intermolecular proximal C1 À C2 bond cleavage of BCB could be utilized for the synthesis of other polycyclic skeletons.S pecifically,w eh ypothesized that intramolecular transannular aldol reactions [24] from in situ generated benzofused eight-membered rings II (Scheme 5) would be within reach when utilizing 1,3-dienes substituted with carbonyl groups with relatively acidic a-hydrogens.A ss hown in Scheme 5, this was indeed the case,o btaining exclusively tricyclic 5a and 5b as single regioisomers and diastereoisomers under otherwise identical reaction conditions to that shown in Scheme 4. Of particular interest was the observation that unsymmetrically disubstituted 1,3dienes could be coupled with excellent yields and as single regio-and diastereoisomers (3h and 3i), with 3h unambiguously characterized by X-ray analysis.…”