A construction of 4,4-spirocyclic γ-lactams by tandem radical cyclization with carbon monoxide

A straightforward synthesis of 4,4-spirocyclic indol γ-lactams by tandem radical cyclization of iodoaryl allyl azides with CO was achieved. The reaction of iodoaryl allyl azides, TTMSS and AIBN under CO pressure (80 atm) in THF at 80 °C gave the desired 4,4-spirocyclic indoline, benzofuran, and oxindole γ-lactams in moderate to good yields.

Introduction 4,4-Spirocyclic oxindole γ-lactams containing a quaternary carbon center are key structures for the synthesis of biologically active natural products and the related analogues [1][2][3][4]. Therefore, the development of an efficient synthesis of this spiro structure is of continued interest for synthetic chemists.
In this study we report a radical cyclization/annulation approach to 4.4-spirocyclic γ-lactams in which CO was intro-Scheme 1: A construction of spirocyclic pyrrolidinyl oxindole by tandem radical cyclization with azide [14].
Based on the known chemistry of radical cyclization and carbonylation reactions, a possible mechanism for the spirocyclization of 1f with CO is shown in Scheme 5. The iodoaryl allyl azide 1f is converted to an aryl radical A via the iodine atom abstraction by the (TMS) 3 Si radical. The subsequent 5-exo cyclization of aryl radical A gives an alkyl radical B, which adds to CO to give an acyl radical C. Finally, the 5-exo addition of acyl radical C onto an azide group takes place with the liberation of dinitrogen to give a cyclized amidyl radical D [29,30], which abstracts hydrogen from TTMSS, affording the 4,4-spirocyclic indoline γ-lactam 2f and a (TMS) 3 Si radical, thus creating a radical chain.
On the other hand, the unusual formation of THF-incorporating lactam 3 from 1g may be rationalized by the consecutive 6-endo cyclization of E and β-elimination of an azidyl radical from the resulting F, to give 2-methylene lactam G (Scheme 6). Then, the THF radical is formed via the α-hydrogen abstraction by the azidyl radical [31][32][33][34], which is attached to G to give α-carbonyl radical H. Finally, H abstracts hydrogen from TTMSS, affording the THF-incorporating product 3 and the (TMS) 3 Si radical, which participates in the next chain reaction.

Conclusion
We have examined a TTMSS-mediated 5-exo radical cyclization/carbonylation/spirocyclization sequence to synthesize 4,4spirocyclic rings. By using this protocol, indoline, benzofuran and oxindole γ-lactams can be conveniently prepared in moderate to good yields. As shown in the contrasting results of acrylic amides 1f and 1g, to cause the requisite 5-exo cyclization of aryl radicals onto allylic azide in preference to the 6-endo cyclization, the angle compression caused by the substitution on the nitrogen has to be considered carefully. Nevertheless, our method can provide a steady tool for the ring formation of 4,4-spirocyclic γ-lactams with the incorporation of CO as a carbonyl group.

Experimental
Typical procedure for a construction of 4,4-spirocyclic γ-lactams by tandem radical cyclization with CO: A