Panowamycins are a group of isochroman-based natural products first isolated from Streptomyces sp. K07-0010 in 2012 by Satoshi Ōmura and co-workers that exhibit modest anti-trypanosomal activity. Herein we demonstrate the first syntheses of these natural products and their epimers. Stereoselective dirhodium-catalyzed C-H insertion reactions with a donor/donor carbene construct the substituted isochroman core in the key bond-forming step. The syntheses are completed without the use of protecting groups and feature a late-stage Wacker oxidation. Incongruent NMR spectra between natural and synthetic samples revealed the structural misassignment of panowamycin A and veramycin F. Computational NMR studies suggested panowamycin A to be an alternate diastereomer, which was confirmed by synthesizing this isomer. Concurrent with this work, in 2021 Mahmud and co-workers came to the same conclusion with an updated NMR analysis of panowamycin A. In a divergent, asymmetric sequence, we report the synthesis of panowamycin A, panowamycin B, TM-135, and veramycin F.

Donor/donor carbenes are relatively new in the field of carbene chemistry; although applications in C-H and X-H insertion reactions are few in number, they demonstrate exquisite chemo- and stereo-selectivity. Recent reports have shown that C-H, N-H, B-H, O-H, S-H, Si-H, Ge-H, Sn-H and P-H insertion reactions are feasible with a variety of transition metal catalysts, both inter- and intramolecularly. Furthermore, high degrees of diastereo- and enantioselectivity have been observed in several cases. Methods typically involve the formation of a diazo-based carbene precursor, but procedures using diazo-free metal carbenes have been developed with significant success. This Minireview covers transition-metal catalyzed insertion reactions with donor/donor and donor carbenes, providing context for future developments in this emerging field.

Polysubstituted allenes are useful synthetic intermediates in many applications, offering structural complexity, modularity, and their axial chirality in further transformations. While acyl and alkoxy-substituted allenes are known, there are currently few examples of allenes containing both functionalities and no reports of geminally substituted acyl/alkoxy allenes being isolated and characterized. Herein, we report the synthesis of tetrasubstituted allenes featuring a novel geminal acyl/alkoxy substitution. These unique "push-pull" allenes are bench-stable and exhibit interesting reactivity in several applications.

Reports of C-H insertions forming six-membered rings containing heteroatoms are rare due to Stevens rearrangements occurring after nucleophilic attack on the carbene by a heteroatom. Using donor/donor carbenes and Rh₂(R-PTAD)₄ as a catalyst, we have synthesized a collection of isochroman substrates in good yield, with excellent diastereo- and enantioselectivity, and no rearrangement products were observed. Furthermore, we report the first synthesis of six-membered rings containing nitrogen by C-H insertion to form tetrahydroisoquinolines. In one case, a Stevens rearrangement product was isolated at elevated temperature from a carbamate-protected amine substrate and computational evidence suggests formation through a free ylide not bound to rhodium.

[This corrects the article DOI: 10.1039/C9SC05111B.].