Intramolecular Polar [4^⊕+2] Cycloadditions of Aryl‐1‐aza‐2‐azoniaallene Salts: Unprecedented Reactivity Leading to Polycyclic Protonated Azomethine Imines

Abstract

The first example of aryl-1-aza-2-azoniaallene salts undergoing a [4⊕ + 2]-cycloaddition reaction in which the azo bond and one aromatic π-bond make up the 4π component is described. This intramolecular reaction appears to be concerted and provides high yields of protonated azomethine imine products that contain a 1,2,3,4-tetrahydrocinnoline core. Substituted alkenes provided products that contain all carbon or nitrogen bearing quaternary centers in high yield.

Intramolecular (4+2) cycloaddition of aryl-1-aza-2-azoniaallene salts: a practical approach to highly sterically-congested polycyclic protonated azomethine imines

“…The new reaction sequence reported here is more environmentally friendly, more practical, higher yielding and has a broader substrate scope than the SbCl 5 mediated process we previously reported. 10…”

“…More recently we reported that aryl-1-aza-2-azoniaallene systems can also react in an unprecedented (4+2) cycloaddition reaction with a pendent alkene to give tricyclic protonated azomethine imine products that containing a 1,2,3,4-tetrahydrocinnoline scaffold (Scheme 1, 7  9). 10 We studied the mechanism of this reaction computationally and showed that it occurs by a concerted (4+2) cycloaddition in which one aromatic π-bond of the heteroallene and the azo bond serve as the 4-π component. 11 This concerted mechanism is consistent with our experimental results that showed that the transformation is stereospecific with respect to the stereochemistry of the alkene; the heteroallenes derived from (Z)-and (E)-hept-5-en-2-one led to diastereomeric cycloaddition products without crossover.…”

“…11 This concerted mechanism is consistent with our experimental results that showed that the transformation is stereospecific with respect to the stereochemistry of the alkene; the heteroallenes derived from (Z)-and (E)-hept-5-en-2-one led to diastereomeric cycloaddition products without crossover. 10 Importantly, the scope of this reaction is fairly general in terms of electronic and steric changes to the alkene portion of the molecule. A variety of alkene substitution patterns were well tolerated including di-and trisubstituted olefins, which led to products containing sterically congested nitrogen-bearing and all-carbon quaternary centers in high yield.…”

“…A variety of alkene substitution patterns were well tolerated including di-and trisubstituted olefins, which led to products containing sterically congested nitrogen-bearing and all-carbon quaternary centers in high yield. 10 We have continued to study this cycloaddition experimentally, and in this paper we describe substrate scope studies with respect to substitution on the N-aryl ring. We also report an improved route to the cycloaddition products that is more practical, more environmentally friendly, and provides remarkably sterically hindered products in high yield.…”

Two-Step Sequence of Cycloadditions Gives Structurally Complex Tetracyclic 1,2,3,4-Tetrahydrocinnoline Products

“…We recently discovered that 1-aza-2-azoniaallene salts, generated by the reaction of SbCl 5 with an α-chloroazo species, can participate in intramolecular [4 + 2]-cycloaddition reactions to give tetracyclic 1,2,3,4-tetrahydrocinnoline products containing an N-aminoiminium motif (Scheme ). Limitations on the preparation of α-chloroazo compounds and the environmental implications of using stoichiometric quantities of SbCl 5 limited the full potential of this transformation and prompted us to look for alternative methods to effect this cycloaddition. Ultimately, we discovered that treating α-trifluoroacetoxyazo compounds with TMS-triflate was a milder and more environmentally friendly way to effect this transformation.…”