A sweeping structural revision of the sarcodonin natural product family (published structures: 1a–13a) is proposed after extensive studies aimed at their chemical synthesis. Key features of revised structure 1b include replacement of the N,N-dioxide moiety with an oxime, ring opening of the central diketopiperazine, and transposition of the terphenyl wing from the 1β-2β position of 1a to the 2β-3β position of 1b. This structure revision arose from the serendipitous synthesis of a benzodioxane aminal (44) whose structure was unambiguously determined by X-Ray crystallography and whose spectral properties bore considerable resemblance to the published data for the sarcodonins. A versatile new method for O-arylation of hydroxamic acids is also reported herein, as well as a manganese(III)-mediated α-oxidation of hydroxamic acids to aminals.

Diastereoselective induction of planar chirality in ferrocenes often employs chiral sulfur-, carbon-or phosphorus-based directing groups. The origin of stereoselectivity in these reactions may be classified as (a) cyclopentadiene (Cp) ring-controlled or (b) base-controlled. These two categories are represented by auxiliaries that typically have stereogenic centers a or g to the ferrocene core, respectively. In this study, it is shown that (À)-2-ferro-imidazol-3-one, the anti-epimer of the previously reported syn-(1R,7aS) substrate, induces lithiation of the pro-R p rather than the pro-S p Cp hydrogen in > 95:5 dr, leading to enantiomers of the syn-derived planar chiral imidazolones upon electrophile quench and elimination. This outcome provides a practical way to prepare planar chiral enantiomers in this series without having to synthesize a more expensive d-proline-derived starting material, since both the syn and anti starting materials are available from a common l-proline-derived intermediate. The origin of stereoselectivity in lithiation of the syn and anti epimers, which have b,g-stereogenic centers, appears to be driven primarily by the conformational bias exerted by the b-silyloxy moiety in each chiral auxiliary, which positions the urea carbonyl within the proximity of one of the two prochiral ortho Cp hydrogens. As such, stereoselectivity is likely Cp ring-controlled for both compounds despite their lack of a-ferrocenyl stereogenic centers. This conclusion is supported by the insensitivity of lithiation selectivity to the bulkiness of the base, comparisons of enantiomers, deuteration experiments, nOe difference studies, and computational modeling of the ground states and lithiation transition states for both substrates.