Recent Progress of Chromium-Mediated Carbonyl Addition Reactions

Organochromium(III) species are versatile nucleophiles in complex molecule synthesis due to their high functional group tolerance and chemoselectivity for aldehydes. Traditionally, carbonyl addition reactions of organochromium(III) species were performed through reduction of organohalides either using stoichiometric chromium(II) salts or catalytic chromium salts in the presence of stoichiometric reductants (such as manganese(0)). Recently, alternative methods emerged involving organoradical formation from readily available starting materials (e.g. N-hydroxyphthalimide esters, alkenes, and alkanes), followed by trapping the radical with stoichiometric or catalytic chromium(II) salts. Such methods, especially using catalytic chromium(II) salts, will lead to the development of sustainable chemical processes minimizing salt wastes and number of synthetic steps. In this review, we describe methods for generation of organochromium(III) species for addition reactions to carbonyl compounds, classified by nucleophiles.

Visible-Light Induced Singlet Nucleophilic Carbenes: Rapid and Mild Access to Fluorinated Tertiary Alcohol Derivatives

Singlet nucleophilic carbenes (SNCs) that contain only one heteroatom donor remain underexplored and underutilized in chemical synthesis. To discover new synthetic strategies that harness these SNCs as reactive intermediates, aromatic or aliphatic siloxy carbenes represent excellent model substrates as they can be readily generated photochemically from stable acyl silane precursors. We herein report the discovery that photochemically generated siloxy carbenes undergo 1,2-carbonyl addition to trifluoromethyl ketones, followed by a silyl transfer process to afford benzoin-type products. This new transformation is a rare example of the use of ketones as trapping reagents for SNC intermediates and delivers an efficient, user-friendly and scalable process to access fluorinated tertiary alcohol derivatives driven by only light, circumventing the use of catalysts or additives.

Visible-Light Induced Singlet Nucleophilic Carbenes: Rapid and Mild Access to Fluorinated Tertiary Alcohol Derivatives

Singlet nucleophilic carbenes (SNCs) that contain only one heteroatom donor remain underexplored and underutilized in chemical synthesis. To discover new synthetic strategies that harness these SNCs as reactive intermediates, aromatic or aliphatic siloxy carbenes represent excellent model substrates as they can be readily generated photochemically from stable acyl silane precursors. We herein report the discovery that photochemically generated siloxy carbenes undergo 1,2-carbonyl addition to trifluoromethyl ketones, followed by a silyl transfer process to afford benzoin-type products. This new transformation is a rare example of the use of ketones as trapping reagents for SNC intermediates and delivers an efficient, user-friendly and scalable process to access fluorinated tertiary alcohol derivatives driven by only light, circumventing the use of catalysts or additives.

Mn(i)-Catalyzed nucleophilic addition/ring expansion via C–H activation and C–C cleavage

The Mn(i)-Catalyzed C–H alkenylation/carbonyl addition/retro-Aldol cascade was realized leading to the convenient synthesis of seven- or eight-membered carbocycles.

Nucleofugal behavior of a β-shielded α-cyanovinyl carbanion

Sterically well-shielded against unsolicited Michael addition and polymerization reactions, α-metalated α-(1,1,3,3-tetramethylindan-2-ylidene)acetonitriles added reversibly to three small aldehydes and two bulky ketones at room temperature. Experimental conditions were determined for transfer of the nucleofugal title carbanion unit between different carbonyl compounds. These readily occurring retro-additions via C–C(O) bond fission may also be used to generate different metal derivatives of the nucleofugal anions as equilibrium components. Fluoride-catalyzed, metal-free desilylation admitted carbonyl addition but blocked the retro-addition.