Tandem Pictet-Spengler/intramolecular

A novel tandem Pictet-Spengler/intramolecular Diels-Alder sequence has been used to prepare carboline derivatives. Reaction of imine 137 with maleic anhydride in CH2CI2 provided cycloadduct 140 in 60-80% yields (Scheme 25) (02TL203). The... 

On the basis of the successful application of intramolecular tandem Pictet-Spengler cyclization of active V-acyliminium intermediates to construct small molecules library embedded with diaza-bridged heterocycles in Section 5.2.1.1, we also developed a solid-... 

For that reason an intramolecular benzannulation was developed, which incorporates all components for the intramolecular alkoxycarbonylation into the naphthoquinone 105 [65]. Based on that strategy a short and convergent pathway for the synthesis of racemic deoxyfrenolicin 108 was accomplished. Xu et al. replaced the allylacetylene 100 in the reaction sequence for nanaomycin A by alkynoate 106. The benzannulation product 107 was an appropriate precursor for a subsequent tandem oxa-Pictet-Spengler cyclisation/DDQ-induced coupling reaction [66]. Following this strategy the total synthesis of enan-tiomerically pure deoxyfrenolicin could be accomplished (Scheme 48). 

Thus /i-carbolincs can be obtained in a tandem hydroformylation/Pictet-Spengler-type intramolecular electrophilic aromatic substitution of polymer bound olefins (Scheme 26) [80]. 

We used this method as the key sequence in the synthesis of ( )-lycopodine (78). The intramolecular isomiinchnone cycloadduct 81 was envisaged as the precursor of the key Stork intermediate 79 (via 80) [42]. The heart of our synthetic plan was the formation of the latter intermediate by a Pictet-Spengler cyclization of the N-acyliminium ion derived from 81. Central to this strategy was the expectation that the bicyclic iminium ion originating from 81 would exist in a chair-like conformation [42,43]. Cyclization of the aromatic ring onto the iminium ion center should take place readily from the axial position. The readily available heptenoic acid 82 would serve as the precursor for the a-dia-zoimide, the direct progenitor of the isomiinchnone dipole. This extension of the tandem cycloaddition-cationic 1-cyclization protocol to the formal synthesis of ( )-lycopodine (78) is outlined below. 

In a very elegant tandem-type combination of such a modified Pictet-Spengler condensation and an initial Pummerer reaction (e.g. Section 4.2.2.4), the polycyclic framework (75) of the erythrina alkaloid (76 Scheme 37) is formed diastereoselectively, in a single step, from (72) in 72% yield the required acyliminium ion (74) is created by an intramolecular alkylation of the intermediate enamide (73)7 ... 

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