Site-selective oxidation, amination and epimerization reactions of complex polyols enabled by transfer hydrogenation

Abstract

Polyoxygenated hydrocarbons that bear one or more hydroxyl groups comprise a large set of natural and synthetic compounds, often with potent biological activity. In synthetic chemistry, alcohols are important precursors to carbonyl groups, which then can be converted into a wide range of oxygen- or nitrogen-based functionality. Therefore, the selective conversion of a single hydroxyl group in natural products into a ketone would enable the selective introduction of unnatural functionality. However, the methods known to convert a simple alcohol, or even an alcohol in a molecule that contains multiple protected functional groups, are not suitable for selective reactions of complex polyol structures. We present a new ruthenium catalyst with a unique efficacy for the selective oxidation of a single hydroxyl group among many in unprotected polyol natural products. This oxidation enables the introduction of nitrogen-based functional groups into such structures that lack nitrogen atoms and enables a selective alcohol epimerization by stepwise or reversible oxidation and reduction.

Iron–PNP‐Pincer‐Catalyzed Transfer Dehydrogenation of Secondary Alcohols

“…Recently, Binder, Ley, and co‐workers reported a commercially available ruthenium complex ( 5 ) as an efficient DH catalyst in a continuous flow method . In the same year, Hartwig and co‐workers reported the selective oxidation of secondary alcohols with a ruthenium‐based complex ( 6 ) . Despite the progress in this field, these catalytic systems all rely on precious metals.…”

A general strategy for diversifying complex natural products to polycyclic scaffolds with medium-sized rings

“…For this reason, C–H functionalization has become one of the major focuses in organic chemistry. C–H functionalization chemistry has been applied to the synthesis of a number of natural products and pharmaceutical reagents 21 , including target-oriented synthesis and last-stage functionalization of natural products 22 . We envisioned that the diversification of natural product skeleta via C–H functionalization would offer a general strategy for the synthesis of many structurally complex and functionally diverse natural product-like small molecules, while simultaneously preparing compounds in an underexplored chemical space.…”

An RCM‐Based Total Synthesis of the Antibiotic Disciformycin B

“…[9] The RCM-product 6 was to be elaborated into disciformycin B (2) by a-selective glycosylation, cleavage of the PMB-ether at C6, esterification, global deprotection, and, in the final step, establishment of the C3-C5 enone moiety by chemoselective oxidation of the allylic hydroxy group. [10] Formation of the enone moiety in the final step would eliminate any potential difficulties arising from the reactivity of this group and/or double bond migration. [5] Tetraene 7 was to be prepared by Mitsunobu esterification of acid 8 and alcohol 9 (vide infra); the latter was envisioned to be accessible from angelic aldehyde (10) [11] by means of asymmetric allylation.…”