A tin-free strategy for the successful cyclization of a variety of internal alkyne-containing N-chloroamine precursors to the ABC core via cyclization of a neutral aminyl radical is established. Deuterium labeling experiments confirm that the solvent is the primary source of the final H atom in the cyclization cascade. These conditions enabled a streamlined route to a β-ketoester intermediate poised for intramolecular Knoevenagel condensation to construct the seven-membered D-ring of calyciphylline A alkaloids. However, exposure to CsF in t-BuOH at elevated temperatures led to an unexpected decarboxylation to form a D-ring-contracted tetracyclic core.

5-exo, 5-exo Cyclizations of conformationally unbiased propargylic aminyl radicals proceed with excellent yield, chemoselectiv ity, and diastereoselectivity under tin-free reductive cyclization conditions, regardless of the electronic environments and intermediate radical stabilization resulting from various olefin substituents. These conditions avoid the need for slow addition of initiator and reductant. By contrast, analogous 6-exo, 5-exo cyclizations require substituents capable of intermediate radical stabilization to avoid premature reduction products. These experimental results are corroborated by computations that further establish the reactivity of these aminyl radicals upon exposure to tin-free cyclization conditions.

T he following corrections were made in Scheme 6 and the first sentence of the paragraph describing it: (1) a missing methyl group was added to 19; (2) step 1 (DIBAL-H, THF, −78 °C) was removed from ent-6 → 19; (3) "2 steps" next to "84% yield" was deleted for ent-6 → 19; (4) the time for PPh 3 , THF is 34 h; the time for LAH is 1.5 h for ent-6 → 19.The text for the paragraph above Scheme 6 was changed to read as follows: At this point, we directed our attention to the synthesis of cyclization precursor ent-5c, derived from known alkynyl azide 7c..." and "Assembly of N-chloroamine ent-5c began with an aza-Wittig reaction of lactol ent-6 with azide 7c...".The corrected Scheme 6 is shown.