November 2023

A range of β-homoprolines was prepared with high anti-selectivity. An intramolecular C–H insertion reaction involving a rhodium alkyl nitrene is a key step in the ring construction. The carboxylic acid in the products can serve as a springboard for further downstream transformations.

Chiral γ-keto sulfones are significant structures in both organic synthesis and pharmaceutical chemistry. Although there are many choices for obtaining racemic forms, only a few enantioselective methods have been reported. We have developed a simple way for obtaining chiral γ-keto sulfones in moderate yields and moderate enantiomeric ratios. Readily available sulfinates were directly used as substrates that could be converted into sulfinic acids by treatment with boric acid. The bifunctional catalyst forms a chiral ion pair with the sulfinic acid and controls the enantioselectivity of the sulfonation through hydrogen bonding.

Fischer indolization using bench-stable sodium arylhydrazine sulfonate as a surrogate of arylhydrazine was developed. The preparation of arylhydrazine sulfonate was also modified by replacing sodium sulfite reductant with Pd-catalyzed hydrogen transfer. The straightforward synthesis of tetrahydrocarbazoles from the corresponding anilines was successfully conducted in a one-pot manner. A practical application of this method was demonstrated in the formal synthesis of pharmaceutical molecules Rizatriptan and Zolmitriptan.

The [4+1] cyclization of a sugar-based epoxytosylate with various C1 dianion equivalents provide highly functionalized homochiral cyclopentane derivatives. For these, a follow-up chemistry was developed to provide various cyclopentane building blocks as starting points for natural product syntheses. The [4+1] domino protocol relies on a 1,4-Brook rearrangement, which is essential for generating the second carbanion.

15N-Labeled azides have a great potential as practical and effective tags for vibrational probing and hyperpolarized magnetic resonance imaging of biomolecules. They can be synthesized by reaction of primary amines with a 15N-labeled diazo-transfer reagent. TfNN15N, a γ-15N-labeled diazo-transfer reagent, was developed to prepare β-15N-labeled azides; these are vibrational probes devoid of strong spectral interference by Fermi resonance. To overcome the stability and safety problems associated with TfNN15N, there is a strong demand for the development of a novel γ-15N-labeled diazo-transfer reagent. We present a study on the diazo-transfer reaction using o-nitrobenzenesulfonyl azide (o-NsN3). o-NsNN15N, a γ-15N-labeled diazo-transfer reagent, was newly developed and found to be better than TfNN15N with respect to its physicochemical properties and ease of synthesis. Unlike TfNN15N, however, o-NsNN15N was found to afford a mixture of β- and γ-15N-labeled azides rather than the β-15N-labeled azide alone. A mechanism for the diazo-transfer reaction of o-NsNN15N with primary amines is proposed to explain the formation of such isotopomeric mixtures.