The synthesis of complex organic compounds usually relies on controlling the reactions of the functional groups. In recent years, it has become possible to carry out reactions directly on the C-H bonds, previously considered to be unreactive. One of the major challenges is to control the site-selectivity because most organic compounds have many similar C-H bonds. The most well developed procedures so far rely on the use of substrate control, in which the substrate has one inherently more reactive C-H bond or contains a directing group or the reaction is conducted intramolecularly so that a specific C-H bond is favoured. A more versatile but more challenging approach is to use catalysts to control which site in the substrate is functionalized. p450 enzymes exhibit C-H oxidation site-selectivity, in which the enzyme scaffold causes a specific C-H bond to be functionalized by placing it close to the iron-oxo haem complex. Several studies have aimed to emulate this enzymatic site-selectivity with designed transition-metal catalysts but it is difficult to achieve exceptionally high levels of site-selectivity. Recently, we reported a dirhodium catalyst for the site-selective functionalization of the most accessible non-activated (that is, not next to a functional group) secondary C-H bonds by means of rhodium-carbene-induced C-H insertion. Here we describe another dirhodium catalyst that has a very different reactivity profile. Instead of the secondary C-H bond, the new catalyst is capable of precise site-selectivity at the most accessible tertiary C-H bonds. Using this catalyst, we modify several natural products, including steroids and a vitamin E derivative, indicating the applicability of this method of synthesis to the late-stage functionalization of complex molecules. These studies show it is possible to achieve site-selectivity at different positions within a substrate simply by selecting the appropriate catalyst. We hope that this work will inspire the design of even more sophisticated catalysts, such that catalyst-controlled C-H functionalization becomes a broadly applied strategy for the synthesis of complex molecules.
The non-natural cyclic amino acids
(1S,3R,4S)-1-amino-3-fluoro-4-(fluoro-18
F)cyclopentane-1-carboxylic acid ([18F]9) and (1S,3S,4R)-1-amino-3-fluoro-4-(fluoro-18
F)cyclopentane-1-carboxylic acid ([18F]28)
have been prepared in 10 and 1.7% decay corrected radiochemical yield,
respectively, and in greater than 99% radiochemical purity. Cell assays
in rat 9L gliosarcoma, human U87 ΔEGFR glioblastoma, and human
DU145 androgen-independent prostate carcinoma tumor cells indicated
that both compounds are substrates for amino acid transport primarily
by system L, with some transport taking place via system ASC. In rats
with 9L gliosarcoma, [18F]9 and [18F]28 provided high tumor to normal brain tissue ratios,
with maximal ratios of 3.5 and 4.1, respectively. Biodistribution
studies in healthy rats confirmed that both compounds are BBB permeable
and that bladder accumulation is low until at least 5 min post injection.
The synthesis of 1,4‐di‐tert‐butyl‐7‐R‐1,4,7‐triazacyclononane (tBu2Rtacn) derivatives through a “crab‐like” cyclization is reported. The tert‐butyl groups were cleavable with concentrated hydrochloric acid, allowing for a facile and convenient synthesis of the HCl salt of H3tacn and the most direct route to its industrially relevant binucleating N‐ethylene bridged derivative, H4dtne. In addition, the synthesis of chiral tacn derivatives with both one and two stereocenters in non‐annulet, alpha‐N positions is reported.
At 2.5 mol % loadings using reaction temperatures between 30-55 °C, ortho-functionalized diaryl diselenides are highly effective organocatalytic oxidants for aerobic redox dehydrative amidic and peptidic bond formation using triethyl phosphite as a simple terminal reductant. This simple-to-perform organocatalytic reaction relies on the ability of selenols to react directly with dioxygen in air without recourse to metal catalysts. It represents an important step toward the development of a general, economical, and benign catalytic redox dehydration protocol.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.