Ring-expanding annulation

The reactions of three-membered ring carbocycles have been exhaustively investigated for decades they are still the subject of active research. As described in this chapter, the inclusion of transition-metal-catalyzed cyclopropane ring-opening reactions is a powerful method for producing useful molecules that are otherwise difficult or impossible to obtain. Alkynes, alkenes, and carbon monoxide can participate in ring-expanding annulation with three-membered carbocycles. 

The most prominent and most successful compound classes in this respect are arguably VCPs and MCPs. The ring-expanding annulations of these substrates provide an opportunity for the synthesis of various medium-sized carbocyclic ring systems. However, the number of examples of asymmetric reactions remains relatively low. Their application in asymmetric catalytic processes is the next challenge to render cyclopropane ring opening more useful and fruitful. 

In a similar manner, terminal alkynes such as 1-14 participate in a Prins/pinacol reaction, resulting in a ring-expanding cyclopentene annulation to give compounds such as 1-15 in high yield (Scheme 1.5) [5]. 

There exists also a synthesis of cyclopentadecanone (VII/81) and ( )-mus-cone, based on a three-carbon annulation of cyclic ketones followed by the regioselective radical cleavage of the zero bridge of the so formed bicyclic system [44], The synthesis of cyclopentadecanone is summarized in Scheme VII/16. The cyclization of VII/78 to the bicyclic alcohol VII/79 proceeds best (94 % yield) with samarium diiodide in the presence of hexamethylphosphoric acid triamide and tetrahydrofuran [45], The oxidative cleavage of VII/79 to the ring expanded product VII/80, was performed by treatment with mercury(II)-oxide and iodine in benzene, followed by irradiation with a 100 Watt high pressure mercury arc. Tributyltinhydride made the de-iodination possible. 

Homoallylic amines containing an allylic hydroxy group rearrange in the presence of an aldehyde and an acid catalyst to yield 3-acylpyrrolidines. If the starting amino alcohol is cyclic, this transformation provides a pyrrolidine-annulated product, in which the initial ring is expanded by one member. The mechanism has been proposed to proceed via a tandem cationic aza-Cope rearrangement/Mannich cyclization1134. 

Trost and Vincent have described an annulation-fragmentation sequence that expands a ring by three atoms (Scheme 3). The methodology has been used to effect a short, high yield synthesis of muscone. 

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