Synlett

A chiral N-2,3,4,5-tetrafluoro-6-iodobenzyl-N-sulfonyl ­aminomethylpyrrolidine tetrafluoroacetic acid salt was designed as an ­iodinated enamine organocatalyst for the enantioselective ­Michael/hemiaminal formation cascade reaction of α,β-unsaturated ­iminoindoles with aldehydes. The use of this iodinated enamine ­catalyst furnished anti-α-carbolinol derivatives in high yields and high stereoselectivities.

The present article presents a personalized Account on the synthesis of nitrogen heterocycles by combination of regioselective Pd-catalyzed cross-coupling reactions of polyhalogenated heterocycles, i.e., Suzuki–Miyaura and Sonogashira reactions, with acid-mediated cycloisomerization reactions. In many cases, the products constitute new heterocyclic core structures and show interesting optical and electronic properties.1 Introduction2 Acridines3 Phenathridines4 Azapyrenes5 Thienoquinolines6 Pyrrolonaphthyridines7 6-Aza-ullazines8 Conclusions

An asymmetric dearomatizative oxidation of 2-naphthol derivatives has been established by organoiodine catalysis, enabling a series of chiral spirooxindoles with various functional groups to be accessed in high yields and high enantioselectivities under mild conditions.

The asymmetric ring opening of azlactones via dynamic kinetic resolution (DKR) is investigated by contrasting thioureas incorporating 1-arylethyl substituents against their more acidic trifluoromethylated analogs. All the catalysts under study outperform Takemoto’s thiourea because of the inclusion of an additional chiral center. However, the difference in yield and selectivity between the fluorinated and non-fluorinated catalysts is minimal. We explain this observation by analysis of calculated transition states. Our findings show that the hydrogen bond (HB) between the NH linked to the 1-arylethyl and the negatively charged oxygen in the benzyloxy ion is the longest in the HB network, whereas the HB between the ammonium group and the same oxygen atom is the shortest. Thus, the substituents and the HB donor ability of this chiral fragment attached to the thiourea are not important in the reaction.

Formal syntheses of teadenols A and B are achieved via a key Pd-catalyzed 6-endo cyclization of a phenol possessing a vinyl ­epoxide moiety. Although 5-exo and 6-endo cyclizations compete during cyclizations of epoxides with a nucleophilic moiety at the 5-position, 6-endo cyclization is realized by using a palladium catalyst.

Daptomycin is a calcium-dependent cyclic lipodepsipeptide antibiotic that is used in the clinic for treating serious infections caused by Gram-positive bacteria. In this account, I present a summary of the research that has been conducted in my group on daptomycin’s total chemical synthesis, its structure–activity relationships, and its mechanism of action, since we began our studies a decade ago.1 Introduction2 Solid-Phase Synthesis of Daptomycin by an On-Resin Cyclization3 α-Azido Acids and Alternative Routes to Daptomycin by On-Resin Cyclization4 Synthesis of Daptomycin by an Off-Resin Cyclization5 SAR Studies on Daptomycin6 Oligomerization of Daptomycin on Membranes7 The Chiral Target of Daptomycin8 SAR Studies on Phosphatidylglycerol9 Conclusions

The C–H borylation strategy has spurred intense research endeavors due to the high atom- and step-economy it represents and because of the broad range of utilities of the resulting organoboranes. Nevertheless, this powerful transformation has had limited substrate scope and poor regioselectivity when it was applied to Lewis basic substrates (e.g., azines). The basic functionalities in substrates can coordinate to the metal centers, hindering the formation of products. Herein, we provide a brief overview of recent advances in transition-metal-­catalyzed regioselective C–H borylation of pyridines. Attention is paid to the latest contributions, which have demonstrated remarkable ­regioselectivity.1 Introduction2 para-Selective C−H Borylation3 meta-Selective C−H Borylation4 ortho-Selective C−H Borylation5 Summary

Direct functionalization of heterocycles is an advanced strategy for diversifying privileged and biorelevant heterocycle-containing molecules. Particularly, use of the most abundant transition metal, iron, as a catalyst makes this process highly cost-effective and sustainable. Recently, some progress has been realized towards the direct functionalization of heterocycles under iron catalysis. Herein, we present the developments in the C–H bond functionalizations and related reactions of various heterocycles by abundant iron salts. This Synpacts is categorized into different sections based on heterocycles being functionalized, and each section is discussed based on the type of reaction catalyzed by iron.1 Introduction2 Functionalization of Indoles2.1 Alkylation2.2 Alkenylation2.3 Other Reactions3 Oxindoles and Isatins3.1 C–C Bond Formation3.2 C–Heteroatom Bond Formation4 Pyridines and Furans5 Functionalization of Azoles6 Summary and Outlook

A palladium-catalyzed synthesis of enantiopure [1,1′-binaphthalene]-2,2′-dicarbonitriles from BINOL-bistriflates and zinc cyanide is reported. This cross-coupling reaction employs a 0.1–5 mol% catalyst loading, and is scalable and stereospecific. The synthetic applications of this reaction are demonstrated by product derivatizations and the synthesis of [1,1′-binaphthalene]-2,2′-bisoxazolines (BOXAX).

As a fungal metabolite, australifungin possesses an α-diketone and a β-ketoaldehyde moiety on its trans-decalin backbone. Microwave-assisted intramolecular Diels–Alder reaction was used as a key strategy to establish the trans-decalin moiety. Further functionalization of the ring B side chain installed the β-ketoaldehyde, one of the two unique functional groups along with the α-diketone.