Aziridinols can be synthesized in moderate to excellent diastereoselective fashion via the addition of organometallic reagents to aziridine-2-carboxaldehydes. The CHO moiety strongly prefers bifurcated geometries relative to the ring, with the oxygen oriented either endo or exo. The aziridine nitrogen remains strongly pyramidalized; invertomeric alternative conformations therefore must be considered. For Bn protected aziridine-2-carboxaldehydes, selectivity originates from chelation. Excellent syn addition selectivity is achieved for N-Bn cis aziridine-2-carboxaldehydes while trans substrates undergo almost completely unselective addition. For this case, as well as the N-Boc protected cis and 2,3-disubstituted systems, the low selectivity seems to be due to the substrates' conformational ambiguity, both between aldehyde endo/exo rotamer and N-invertomer structures. However, for the N-Boc trans substrates, extremely high syn selectivity is observed, which is unaffected by chelation modifiers. This strong stereopreference appears to be dictated by the chelation-like favorable interaction between the aldehyde carbonyl and the syn-Boc group's carbon. For the N-Ts protected series, diastereoselectivity is largely understandable in terms of the systems' conformational preferences. Though cis substrates do not enjoy any kind of selectivity, their trans analogues afford the product with moderate to high syn selectivity, while exceptional stereospecificity is achieved in the case of N-Ts-2,3-disubstituted aziridine-2-carboxaldehyde. The assembly of appropriately stereo-defined aziridinols has paved the way to our discovery of a one-pot tandem aza-Payne/hydroamination reaction; a process that yields highly functionalized densely substituted pyrrolidines. A number of transformations have been revealed to derive a diverse range of interesting scaffolds, which can be used as advanced intermediates toward the synthesis of natural products. The total synthesis of salinosporamide A, currently underway, is an example of the latter point. Scope of such transformation is not limited only to the pyrrolidine rings, piperidines can also be accessed via exploiting a similar concept. Replacement of the alkyne functionality with an a,b-unsaturated carbonyl tethered in a stereodefined aziridinol allows entry to six member heterocyclic rings. These modified aziridinols can be accessed via a highly stereoselective Baylis-Hillman reaction of N-Ts 2,3-substituted aziridine-2-carboxaldehydes. Outcome of the tandem aza-Payne/hydroamination can also be altered via trapping the aza-Payne intermediate with CO2, leading to a latent nucleophile that yields N-Ts enamide carbonates upon intramolecular hydroamination of the pendant alkyne. The latter can be elaborated towards the synthesis of biologically interesting 3,4-dihydroxy pyrrolidinones.
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