To achieve a concise and modular synthesis strategy, we integrated an oxidative Rh(III)-catalyzed C-H functionalization (see SI) previously developed in the Kou lab that combines densely substituted enol silanes 7 with hydroxamic esters 8 to produce densely substituted 3hydroxydihydroisoquinolones 9, which upon treatment with aqueous HCl, eliminate water to form isoquinolones 10a-k in 24-76% yields after two steps (Scheme 1a). Given the multi-substitution patterns of the compound precursors, which are more complex than those reported in the original study, the reactivity and modest yields are remarkable. Our pursuit of oxidative C-H functionalization with enol silanes solves a major limitation in alkyne reactivity: enol silanes 7 are surrogates for terminal alkynes, which are poorly precedented in C-H functionalization, with the exception of a recent study by the Pfizer Oncology group demonstrating success with propyne. This methodology was effective in introducing multiple substitution patterns, including a bromide functional handle, into rings A and D. A ligand-free palladium-catalyzed cross-coupling was optimized to append a vinyl group, generating styrene derivatives 11 in up to 98% yields. The presence of an aldehyde in aryl bromide 10b hampers productive crosscoupling, whereas aldoxime 10c undergoes competitive palladium-catalyzed aldoxime rearrangement, 12 generating benzamide side-product 11c' (37%) alongside the target Suzuki product (25%). These reactions set the stage for Ndeprotection coupled to a novel anionic 6π-azaelectrocyclization. This process bypasses an otherwise multistep hydroboration/oxidation/activation/cyclization sequence 13 and directly furnishes the tetracyclic alkaloid core in 20-84% yields (Scheme 1b). In contrast to the syntheses of tetramethoxyoxyberberines ( ) and ( ) where NaH (3 equiv) mediated a tandem N-O cleavage and 6πaza-electrocyclization in 20 hours without additional additives, NaH induced N-O cleavage but only partial cyclization in all other examples. To circumvent this, we devised a one-pot protocol whereby KOt-Bu (0.5 equiv) is added following N-deprotection and additionally reacted for 18-22 hours to fully convert the reactant and complete the electrocyclization. Moderate to good yields (42-84%) were generally observed when the oxyberberine D-rings were electron-neutral (e.g., 4, 16, 17) or electron poor (e.g., 18, 19). In contrast, lower isolated yields (15-31%) were obtained when the D-ring was substituted with electrondonating groups (i.e., 3, 14, 20, 21). The reduction in yield is attributed to sensitivity of the oxyberberine alkaloids to silica gel and alumina treatments, rather than inefficiencies in the electrocyclization reaction. In all cases, the electrocyclization produces high yields as determined by NMR analysis. Of note, the Suzuki reaction of aryl halide 10f is accompanied by N-O cleavage, producing only deprotected isoquinolone 11f' in 18% yield. Aryl halide 10k with the three aryl halide bonds decomposes under the reaction conditions and therefore could not be converted to 11k. In the cases of stepharotudine (4) and methoxystepharotudine 20, their 5-exo-trig cyclization counterparts 4-iso (2%) and 5-iso (3%) were also formed as minor side-products and represent B-ring distortion analogs of stepharotudine. Oxidation of 8-oxypseudopalmatine (3) led to the first preparation of the naturally occurring prepseudopalmatine (2) in 48% isolated yield.