C-Alkylation of alkali metal carbanions with olefins.

C-Alkylations of alkali metal carbanions with olefins, first reported five decades ago, is a class of reaction undergoing a resurgence in organic synthesis in recent years. As opposed to expectations from classical chemistry and transition metal-catalysis, here olefins behave as closed-shell electrophiles. Reactions range from highly reactive alkyllithiums giving rise to anionic polymerization, to moderately reactive alkylpotassium or alkylsodium compounds that give rise to defined, controlled and bimolecular chemistry. This review presents a brief historical overview on C-alkylation of alkali metal carbanions with olefins (typically mediated by KOtBu and KHMDS), highlights contemporary applications and features developing mechanistic understanding, thereby serving as a platform for future studies and the widespread use of this class of reaction in organic synthesis.

Benzoates as photosensitization catalysts and auxiliaries in efficient, practical, light-powered direct C(sp3)-H fluorinations.

Of the methods for direct fluorination of unactivated C(sp3)-H bonds, photosensitization of SelectFluor is a promising approach. Although many substrates can be activated with photosensitizing catalysts, issues remain that hamper fluorination of complex molecules. Alcohol- or amine-containing functional groups are not tolerated, fluorination regioselectivity follows factors endogenous to the substrate and cannot be influenced by the catalyst, and reactions are highly air-sensitive. We report that benzoyl groups serve as highly efficient photosensitizers which, in combination with SelectFluor, enable visible light-powered direct fluorination of unactivated C(sp3)-H bonds. Compared to previous photosensitizer architectures, the benzoyls have versatility to function both (i) as a photosensitizing catalyst for simple substrate fluorinations and (ii) as photosensitizing auxiliaries for complex molecule fluorinations that are easily installed and removed without compromising yield. Our auxiliary approach (i) substantially decreases the reaction's induction period, (ii) enables C(sp3)-H fluorination of many substrates that fail under catalytic conditions, (iii) increases kinetic reproducibility, and (iv) promotes reactions to higher yields, in shorter times, on multigram scales, and even under air. Observations and mechanistic studies suggest an intimate 'assembly' of auxiliary and SelectFluor prior/after photoexcitation. The auxiliary allows other EnT photochemistry under air. Examples show how auxiliary placement proximally directs regioselectivity, where previous methods are substrate-directed.

An organophotocatalytic late-stage N-CH3 oxidation of trialkylamines to N-formamides with O2 in continuous flow.

We report an organophotocatalytic, N-CH3-selective oxidation of trialkylamines in continuous flow. Based on the 9,10-dicyanoanthracene (DCA) core, a new catalyst (DCAS) was designed with solubilizing groups for flow processing. This allowed O2 to be harnessed as a sustainable oxidant for late-stage photocatalytic N-CH3 oxidations of complex natural products and active pharmaceutical ingredients bearing functional groups not tolerated by previous methods. The organophotocatalytic gas-liquid flow process affords cleaner reactions than in batch mode, in short residence times of 13.5 min and productivities of up to 0.65 g per day. Spectroscopic and computational mechanistic studies showed that catalyst derivatization not only enhanced solubility of the new catalyst compared to poorly-soluble DCA, but profoundly diverted the photocatalytic mechanism from singlet electron transfer (SET) reductive quenching with amines toward energy transfer (EnT) with O2.