Yang cydization reaction

Highly enantioselective atom transfer radical cydization reactions catalyzed by chiral Lewis acids have been reported by Yang et al. [80]. Two main advantages of these enantioselective cyclizations include installing multiple chiral centers and retaining a halogen atom in the product, which allows for further functionalization. 

The latter example (reaction 36) already indicates that the Yang cydization can also be used to synthesize four-membered heterocycles. After light absorption, the a,(3-unsaturated carbonyl compound 84 undergoes intramolecular hydrogen abstraction at the a-position of the carbonyl moiety (reaction 37), leading to the 1,4-biradical intermediate XXX [87]. A radical combination then efficiently yields the spirocyclic P-lactam derivative 85, and only one stereoisomer is formed in this case. In this transformation, the a,P-unsaturated carbonyl function can be considered as being vinylogous to a simple ketone. 

Liu, L., Gao, Y, Che, C., Wu, N., Wang, D.Z., Li, C.C., and Yang, Z. (2009) A model study for the concise construction of the oxapentacyclic core of cortistatins through intramolecular Diels-Alder and oxidative dearomatization-cydization reactions. Chem. Commun., 662-664. 

Another Lewis add-catalyzed atom-transfer domino radical cydization, to produce various bicydic and tricyclic ring skeletons, has been developed by Yang and coworkers [54], Reactions of the a-bromo- 3-keto ester 3-125 with Yb(OTf) 3 and Et3B/02 led to the bicyde 3-126 in 85 % yield (Scheme 3.33). The reaction proceeds via a 6-ertdo-trig and 5-exo-trig cyclization after initial abstraction of the bromine... 

Yang has reported a related tandem cydization for the synthesis of pyrroloindoline derivatives that also proceeds though a mechanism involving alkene aminopalladation followed by carbopalladation of a second alkene [46]. As shown below, the 2-allylaniline derivative 48 was converted to 49 in 95% yield through treatment with a catalyst composed of Pd(OAc)2 and pyridine (Eq. (1.22)). Use of (-)-sparteine as a ligand in this reaction provided 49 with up to 91% ee. 

---