Given the efficiency with which the a-branched secondary alkylamines could be assembled via this visible-light-driven CAA process, we questioned whether deployment of an alkyl iodide containing a tethered leaving group might enable a subsequent cyclization to form a-substituted N-heterocyclic frameworks in a multicomponent fashion. Specifically, after the CAA process, cyclization via displacement of a pendant chloride would generate a cyclic amine bearing N-substitution controlled by choice of amine, a-substitution controlled by choice of aldehyde, and ring size controlled by choice of the chloroalkyl iodide reagent. Evaluating this process using panisidine (1b), 4-fluorobenzaldehyde (2c) and chloroiodomethane (5a), we found heating the b-chloro amine CAA derivative 6a in the presence of t BuOK for 30 min gave the a-branched aziridine 7a in good yield (Figure ). Chromatographic purification of the intermediate chloro amines was not required, although we observed higher yields when removing excess silane, alkyl iodide and aldehyde by strong cation exchange (SCX) filtration before performing the cyclisation. The use of 1-chloro-3-iodopropane (5b) delivered pyrrolidines 7b and 7c directly after basic aqueous workup without the need for a separate cyclisation procedure, reflecting the facile 5-exo ring-closure of saturated 5membered rings. Piperidine 7d was obtained by heating echloro amine CAA product 6d in the presence of base and catalytic sodium iodide in acetonitrile for 2 h. We note the high yields (³ 70%) of the CAA reaction when using functionalised alkyl iodides 5a-c with amine 1b and aldehydes 2c and 2e, demonstrating that consistently high efficiency can be achieved with challenging alkyl iodides under our conditions with favourable amine and aldehyde coupling partners. The ability to obtain a-branched N-heterocycles directly from feedstock amines and aldehydes with a programmable ring size dictated by choice of a commercial bifunctional lynchpin (5a-c) represents a valuable approach that is complementary to existing methods. Moreover, we recognized that the leaving group need not be confined to the alkyl iodide component, and that the same annulation strategy should be effective with the aldehyde component carrying the chloride leaving group and the alkyl iodide component carrying the eventual a-substituent. Indeed, a reaction using primary alkylamine 1c, 5chloropentanal (2f), and isopropyl iodide followed by cyclisation of the e-chloro amine CAA product provided abranched piperidine 7f in 64% yield over two steps (Figure ). These results suggest that a straightforward and general multicomponent approach to saturated nitrogen heterocycles may be possible with further optimization-studies in this regard are ongoing and will be reported in due course. A longstanding challenge in amine synthesis has been the development of alkylation processes that are selective between primary and secondary amines. With this in mind, we questioned how a molecule containing both a primary and a secondary amine would react under the new conditions. Accordingly, we submitted 4-aminomethylpiperidisne (9a) to the HFIP-mediated CAA reaction with cyclohexane carboxaldehyde (2b) and isopropyl iodide (3a), and were surprised to find that only trace quantities of product arising from the CAA reaction (at either amine) could be observed (Figure ). Given the effectiveness of TMSCl as an additive in the main substrate scope, we also evaluated the reaction in the presence of two equivalents of TMSCl. Remarkably, 1 H NMR analysis of the crude reaction mixture appeared to show the formation of a single product in 87% assay yield. While we were able to obtain pure diamine 10a in low yield (see Supporting Information) we were unable to find conditions that provided 10a in a yield commensurate with the assay. However, selective protection of the piperidine nitrogen as the Boc-carbamate gave the corresponding mono-Boc diamine (Boc-10a), which could be isolated in 66% yield via chromatography on neutral alumina (Figure ). As such, all diamines generated through this reaction were isolated as their mono-Boc derivatives. Although analysis of the crude CAA reaction mixture by 1 H NMR shows a remarkably clean reaction profile, analysis by LCMS elucidates that the reaction is not perfectly selective, and by-products derived from reductive amination and CAA reactivity can be observed. Nonetheless, the fact that products derived from a single CAA reaction at the primary amine can be isolated from the reaction mixture in yields typically exceeding 50% demonstrates a significant bias for the formation of these products. At the present stage of development, the origin of this unexpected selectivity remains unclear; however, studies in this regard are ongoing and will be reported in due course. The selective reactivity of the starting diamine was replicated over several combinations of aldehyde and alkyl iodide to form the desired products 10b-10f with a scope reflecting that of the standard reaction: heterocyclic (10b), aromatic (10c) and acyclic (10d) aldehydes could be incorporated, as could primary (10e) and tertiary (10f) alkyl iodides. We were pleased to find that this selectivity could be extended to a diamine containing a benzylamine as the primary amine and a piperidine as the secondary amine, with the CAA reaction taking place selectively at the benzylamine nitrogen (10g). A diamine containing a benzylamine as the primary amine and a pyrrolidine as the secondary amine also reacted selectively at the benzylamine nitrogen (10h), however, a challenging purification led to a diminished isolated yield. A limitation of this method is the necessity of a cyclic secondary amine to impart selectivity: diamines containing acyclic secondary amines reacted unselectively. However, some selectivity was observed in a sterically biased system, and compound 10i was obtained in a good assay yield. Furthermore, we note that the use of abranched aldehydes is required in order to impart this primaryover-cyclic-secondary amine reactivity; use of unbranched aldehydes resulted in complex mixtures. Finally, given our ability to selectively protect the cyclic secondary amine in the presence of the acyclic a-branched secondary amine derived from the CAA no additive: trace with TMSCl: trace scope of selective primary amine functionalisation reaction, we questioned whether it might be possible to selectively functionalize the cyclic amine to achieve a formal four-component coupling to complex diamine-derived products. Accordingly, we heated 10a (obtained from SCX filtration of the crude reaction mixture) to 100 °C in the presence of a heteroaryl electrophile (Figure ). We were pleased to find that arylation took place exclusively at the piperidine nitrogen, providing 10j in 69% yield after chromatography. We believe that this four-component coupling demonstrates a powerful approach to the rapid assembly of complex nitrogen-containing scaffolds through the modular incorporation of commercial building blocks.