The asymmetric synthesis of a range of axially chiral 2-arylpyridines by a cobalt-catalyzed [2 + 2 + 2] cycloaddition reaction is described. The use of a planar chiral (1-neomenthylindenyl)cobalt(COD) complex under photochemical conditions is the key for reacting the 1-naphthyldiynes with a range of differently functionalized nitriles, giving the enantiomeric atropoisomers with high chemical yields and enantiomeric excesses of up to 94% ee.

A series of different unsymmetrically substituted naphthyl-based diynes were synthesized. These substrates formed the foundation for the assembly of novel biaryls containing pyridine moieties with differently substituted five-membered rings in the backbone of the newly formed heterobiaryl system. The key step for their efficient construction was the photo- and cobalt-catalyzed [2 + 2 + 2] cycloaddition reaction between the corresponding naphthyldiyne and aceto- or benzonitrile. The heterobiaryl products have been isolated and investigated with respect to the configurational stability of their biaryl axis using dynamic chiral HPLC; subtle effects of the substitution pattern on the stability of the axis were observed. For several compounds the activation barriers (ΔG(‡)) of racemization were determined. Suitable substitution of the five-membered ring backbone exemplarily allowed the Co-catalyzed enantioselective cyclization to yield the enantiomerically enriched heterobiaryl.

Two routes, one destination: The metal‐free, uncatalyzed [2+2+2] cycloaddition of cyanodiynes can proceed through two different reaction cascades, both yielding pyridines as products (see scheme). The unactivated cyano group can act either as an enophile in Alder–ene or as a dienophile in hetero‐Diels–Alder reactions—both of which are rather uncommon for this well‐known functional group.

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The synthesis protocol for the preparation of different arylpropiolic acids using the Negishi reaction and the addition of HCl to the alkyne moiety of these acids in subsequent esterification reactions using SOCl 2 was examined.Functionalized acetylenes today are a basic building block for the preparation of complex organic molecules. 1 Prominent uses include substance classes like ynamides, alkynylphosphines, enynes, halogenated alkynes, and many more. 2 For the elaboration of complex structures containing alkyne moieties cross-coupling reactions like the Sonogashira reaction gained unprecedented importance due to their high versatility and most often mild conditions and chemoselectivity. 3 The Sonogashira reaction is also regularly used for the assembly of starting materials for studies on asymmetric cobalt-catalyzed cycloaddition reactions, utilizing functionalized diynes. 4 These investigations often require also the introduction of different functional groups like ester, amide, ketone, or amine connected to the alkyne, frequently employing standard coupling procedures for connecting two single functionalized alkynes, for example, esterification reactions. 5During our synthetic studies we needed to synthesize diyne 5, in which the triple bonds are connected by an ester group (for the strategic bond connections, see Scheme 1).Our approach was aimed at the synthesis of arylpropiolic acid 3 via ester 2, conversion to the acid chloride 4, and esterification with propargyl alcohol under standard conditions using a nucleophilic catalyst (Scheme 2). However, this simple synthetic scheme turned out to be not as simple as we thought. In the first step, the arylpropiolic acid ester 2 was prepared from 1-iodo-2-methoxynaphthalene and the organozinc reagent 1 by a modified procedure using the Negishi reaction in excellent yields, after the Sonogashira reaction had yielded only minor amounts of 2. 6 Following the hydrolysis of ester 2, the obtained acid 3 was treated with thionyl chloride under moderate conditions to yield the acid chloride 4. The final esterification with propargylic alcohol was done in the presence of 4-dimethylaminopyridine (DMAP) in dichloromethane.To our surprise 6 was exclusively isolated in up to 57% yield after repeated attempts. The formation of 6 is evident from the 1 H NMR spectrum by the presence of the Scheme 1 Key steps for the synthesis of diyne 5 connected by an ester group

Die vergleichbare Herstellung von Pyridinen aus Cyandiinen ist von der Ausgangssituation her komplizierter, da die Nitrilgruppe weder ein besonders geeignetes Enophil in Alder-En-Reaktionen noch ein Dienophil in Diels-Alder-Reaktionen ist. Es gibt nur sehr wenige Beispiele für Cyan-EnReaktionen mit Olefinen, bei denen zudem starke LewisSäuren wie BCl 3 zur Aktivierung des Nitrils notwendig sind. [7] Eine weitere selten genutzte Möglichkeit ist die Verwendung von in situ erzeugten Nitriloxiden als Enophile zur Herstellung von cyclischen Oximen aus acyclischen Vorstufen.[8] Schema 1. Übergangsmetallfreie Cyclotrimerisierung von Triinen (grü-ne und orangefarbene Bindungen: ursprüngliche Alkinbindungen, blaue Bindungen: neu gebildete Bindungen; die gekrümmten Pfeile sollen die Bindungsneubildungen verdeutlichen).

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