Electrochemistry-Enabled C-Heteroatom Bond Formation of Alkyl Germanes.

Because of their robustness and orthogonal reactivity features, alkyl germanes bear significant potential as functional handles for the construction of C(sp3)-rich scaffolds, especially in the context of modular synthetic approaches. However, to date, only radical-based reactivity has been accessible from these functional handles, which limits the types of possible decorations. Here, we describe the first general C(sp3)-heteroatom bond formation of alkyl germanes (-GeEt3) by leveraging electrochemistry to unlock polar reactivity. This approach allowed us to couple C(sp3)-GeEt3 with a variety of nucleophiles to construct ethers, esters, amines, amides, sulfonamides, sulfides, as well as C-P, C-F, and C-C bonds. The compatibility of the electrochemical approach with a modular synthetic strategy of a C1 motif was also showcased, involving the sequential functionalization of Cl, Bpin, and ultimately GeEt3 via electrochemistry.

Triply Selective & Sequential Diversification at Csp 3: Expansion of Alkyl Germane Reactivity for C-C & C-Heteroatom Bond Formation.

We report the triply selective and sequential diversification of a single Csp 3 carbon carrying Cl, Bpin and GeEt3 for the modular and programmable construction of sp3-rich molecules. Various functionalizations of Csp 3-Cl and Csp 3-BPin (e.g. alkylation, arylation, homologation, amination, hydroxylation) were tolerated by the Csp 3-GeEt3 group. Moreover, the methodological repertoire of alkyl germane functionalization was significantly expanded beyond the hitherto known Giese addition and arylation to alkynylation, alkenylation, cyanation, halogenation, azidation, C-S bond formation as well as the first demonstration of stereo-selective functionalization of a Csp 3-[Ge] bond.

Recent Developments with Organogermanes: their Preparation and Application in Synthesis and Catalysis.

Within the sphere of traditional Pd0 /PdII cross coupling reactions, organogermanes have been historically outperformed both in terms of scope and reactivity by more conventional transmetalating reagents. Subsequently, this class of compounds has been largely underutilized as a coupling partner in bond-forming strategies. Most recent studies, however, have shown that alternative modes of activation of these notoriously robust building blocks transform organogermanes into the most reactive site of the molecule-capable of outcompeting other functional groups (such as boronic acids, esters and silanes) for both C-C and C-heteroatom bond formation. As a result, over the past few years, the literature has increasingly featured methodologies that explore the potential of organogermanes as chemoselective and orthogonal coupling partners. Herein we highlight some of these recent advances in the field of organogermane chemistry both with respect to their synthesis and applications in synthetic and catalytic transformations.

Orthogonal Olefination with Organogermanes.

Reported herein is a fully orthogonal olefination, which involves the site- and E-selective coupling of aryl germanes with alkenes, tolerating otherwise widely employed coupling handles such as aromatic (pseudo)halogens (C-I, C-Br, C-Cl, C-F, C-OTf, C-OSO2 F), silanes and boronic acid derivatives as well as alternative functionalities. This unprecedented [Ge]-based oxidative Heck coupling proceeds at room temperature with high speed (10 min to 2 hours) and operational simplicity owing to its base-free and air-tolerant features.

Diastereo-, Enantio-, and Z-Selective α,δ-Difunctionalization of Electron-Deficient Dienes Initiated by Rh-Catalyzed Conjugate Addition.

Metal-catalyzed enantioselective conjugate additions are highly reliable methods for stereoselective synthesis; however, multicomponent reactions that are initiated by conjugate arylation of acyclic π-systems are rare. These reactions generally proceed with poor diastereoselectivity while requiring basic, moisture sensitive organometallic nucleophiles. Here, we show that Rh-catalysts supported by a tetrafluorobenzobarrelene ligand (Ph-tfb) enable the enantio-, diastereo-, and Z-selective α,δ-difunctionalization of electron-deficient 1,3-dienes with organoboronic acid nucleophiles and aldehyde electrophiles to generate Z-homoallylic alcohols with three stereocenters. The reaction accommodates diene substrates activated by ester, amide, ketone, or aromatic groups and can be used to couple aryl, alkenyl, or alkyl aldehydes. Diastereoselective functionalization of the Z-olefin unit in the addition products allows for the generation of compounds with five stereocenters in high dr and ee. Mechanistic studies suggest aldehyde allylrhodation is the rate-determining step, and unlike reactions of analogous Rh-enolates, the Rh-allyl species generated by δ-arylation undergoes aldehyde trapping rather than protonolysis, even when water is present as a cosolvent. These findings should have broader implications in the use of privileged metal-catalyzed conjugate addition reactions as entry points toward the preparation of acyclic molecules containing nonadjacent stereocenters.