Dual Photoredox/Nickel Catalysis Enables Diastereoselective Synthesis of Multisubstituted γ-Lactams Using Alkyl-GeMe3 as Radical Precursors.

Herein, we report a single-step, multicomponent approach to versatile γ-lactams through dual photoredox/nickel-catalyzed dicarbofunctionalization of α,ß-unsaturated γ-butyrolactam. This reaction utilized alkyl trimethylgermanium as a radical precursor and acyl chloride as the electrophile, demonstrating remarkable functional group compatibility.

Alkyl-GeMe3 : Neutral Metalloid Radical Precursors upon Visible-Light Photocatalysis.

Single-electron transfer (SET) oxidation of ionic hypervalent complexes, in particular alkyltrifluoroborates (Alkyl-BF3 - ) and alkylbis(catecholato)silicates (Alkyl-Si(cat)2 - ), have contributed substantially to alkyl radical generation compared to alkali or alkaline earth organometallics because of their excellent activity-stability balance. Herein, another proposal is reported by using neutral metalloid compounds, Alkyl-GeMe3 , as radical precursors. Alkyl-GeMe3 shows comparable activity to that of Alkyl-BF3 - and Alkyl-Si(cat)2 - in radical addition reactions. Moreover, Alkyl-GeMe3 is the first successful group 14 tetraalkyl nucleophile in nickel-catalyzed cross-coupling. Meanwhile, the neutral nature of these organogermanes offset the limitation of ionic precursors in purification and derivatization. A preliminary mechanism study suggests that an alkyl radical is generated from a tetraalkylgermane radical cation with the assistance of a nucleophile, which may also result in the development of more non-ionic alkyl radical precursors with a metalloid center.

Alkyl Carbagermatranes Enable Practical Palladium-Catalyzed sp2-sp3 Cross-Coupling.

Pd-catalyzed cross-coupling reactions have achieved tremendous accomplishments in the past decades. However, C(sp3)-hybridized nucleophiles generally remain as challenging coupling partners due to their sluggish transmetalation compared to the C(sp2)-hybridized counterparts. While a single-electron-transfer-based strategy using C(sp3)-hybridized nucleophiles had made significant progress recently, fewer breakthroughs have been made concerning the traditional two-electron mechanism involving C(sp3)-hybridized nucleophiles. In this report, we present a series of unique alkyl carbagermatranes that were proven to be highly reactive in cross-coupling reactions with our newly developed electron-deficient phosphine ligands. Generally, secondary alkyl carbagermatranes show slightly lower, yet comparable activity to its Sn analogue. Meanwhile, primary alkyl carbagermatranes exhibit high activity, and they were also proved stable enough to be compatible with various reactions. Chiral secondary benzyl carbagermatrane gave the coupling product under base/additive-free conditions with its configuration fully inversed, suggesting that transmetalation was carried out in an "SE2(open) Inv" pathway, which is consistent with Hiyama's previous observation. Notably, the cross-coupling of primary alkyl carbagermatranes could be performed under base/additive-free conditions with excellent functional group tolerance and therefore may have potentially important applications such as stapled peptide synthesis.

Palladium-Catalyzed Cross-Coupling of Tertiary Cyclopropyl Carbagermatranes with Acyl Chlorides.

A simple method for the synthesis of cyclopropane compounds via cross-coupling reaction between tertiary cyclopropyl carbagermatranes and acyl chlorides was reported. Derivatives of acryloyl chloride and aliphatic acyl chloride also performed to be suitable substrates. This process can be used to introduce a wide range of functionalized cyclopropane groups and acyl groups directly.