With an optimized set of reaction conditions in hand, we explored the scope of this transformation by first varying the amine component, using cyclohexanecarboxaldehyde (Fig. ) and 2-iodopyridine (3a) as representative coupling partners. Both assay yield and yield of isolated product are quoted in all cases to provide a measure of reaction efficiency separated from isolation of materials, which is frequently problematic with tertiary alkylamines. A range of cyclic, bicyclic, spirocyclic and heterocyclic secondary amines were smoothly converted to the corresponding α-alkyl 2-azinyl tertiary alkylamines (Fig. ), allowing for the incorporation of a broad selection of pharmaceutically ubiquitous features arising from the diversity of the abundant secondary alkylamine feedstock. Primary amines and anilines, however, consistently performed poorly in the reaction, frequently resulting in complex product mixtures. For example, using panisidine (1l) as the amine component gave the corresponding secondary amine product 4l with a low assay yields and challenging purification precluded accurate yield determination (see Supplementary Information, Section 7.2). However, N-methyl-p-anisidine (1k) was capable of coupling to give N-aryl tertiary amine 4k in good yield, suggesting an important role of the intermediate iminium ion. N,N-dialkylamines displaying linear functionalized alkyl substituents, including aromatic and tetrazole containing groups, gave tertiary amines 4m-4q. The use of benzyl and allylamine derivatives gives rise to products that can be readily transformed to the corresponding primary and secondary amines (4n, 4q) for downstream diversification. Several secondary amine-containing drugs, drug fragments and a natural product were accommodated in the reaction, producing tertiary amine derivatives 4r-4w and demonstrating a compatibility of the reaction with more complex functionality. We were pleased to find that, in many cases, amines with multiple Lewis basic functionalities were well tolerated in this reaction. As an additional feature, the reaction was found to be amenable to the use of amine hydrochloride salts -a form in which they are often supplied -by lowering the amount of TMSOTf required to substoichiometric levels; the hydrochloride salt is presumed to assist the iminium ion formation and hence there is less reliance on the TMSOTf additive to promote this step. Next, we surveyed the scope of the reaction in the aldehyde component using amine 1x and 2-iodopyridine 3a as representative coupling partners (Fig. ). Accordingly, a variety of aliphatic (Fig. ) and aromatic (2aj-2ap) aldehydes were successfully coupled in the carbonyl azinylative amination reaction to give amine products which we, upon inspection, would expect to possess favorable pharmacokinetic properties as orally available agents: molecular weights ranging from 300-500 Da and between five to eight H-bond acceptors. Both linear aldehydes and α-branched aldehydes, including carbocycle and heterocycle-containing, were readily converted to amines 4x-4ai. The reaction of a substituted cyclopropyl aldehyde resulted in formation of the expected amine 4ae without any trace of strained ring-opening products. This radical clock experiment suggests that the reaction pathway does not go through an indium-mediated iminium reduction to an α-amino radical and subsequent addition-elimination to the 2-iodo pyridine. A range of aromatic and heteroaromatic aldehydes could be used, giving rise to (hetero)benzhydrylamine derivatives 4aj-4ap. These amines, which contain the α-aryl, α'-2-azinyl methylamine motif but can be challenging to access by traditional methods. Some heteroaromatic aldehydes, such as 2-pyridinecarboxaldehyde, lead to poor yields of the desired products (2aq) and reductive amination was observed as the predominant reaction pathway. However, use of several Lewis-basis heteroaryl aldehydes generated the methylamine motive substituted with two heteroarenes in synthetically useful yields (2ao-p, 2ar), the products of which display up to seven heteroatoms.