Catalytic Generation of Carbanions through Carbonyl Umpolung

Abstract

Carbonyl Umpolung is a powerful strategy in organic chemistry to construct complex molecules. Over the last few years, versatile catalytic approaches for the generation of acyl anion equivalents from carbonyl compounds have been developed, but methods to obtain alkyl carbanions from carbonyl compounds in a catalytic fashion are still at an early stage. This Minireview summarizes recent progress in the generation of alkyl carbanions through catalytic carbonyl Umpolung. Two different catalytic approaches can be utilized to enable the generation of alkyl carbanions from carbonyl compounds: the catalytic Wolff–Kishner reaction and the catalytic single‐electron reduction of carbonyl compounds and imines. We discuss the reaction scope, mechanistic insights, and synthetic applications of the methods as well as potential future developments.

Light‐Induced Transformations of Donor‐Donor Diazo Compounds Derived from N‐Sulfonylhydrazones

“…The chemistry of N ‐sulfonylhydrazones has been widely explored under thermal conditions, either with/or without transition‐metal catalysts, and discussed in many reviews [3] . In 2020, König reported the umpolung reactivity of carbonyl compounds [10] via radical addition to N ‐sulfonylhydrazone followed by elimination of nitrogen and then quenched with electrophile in the presence of photo‐redox catalysts and radical precursors, etc., summarized elsewhere [11] . Similar reaction was observed by Zeng group with N ‐sulfonylhydraones [12] .…”

“…[3] In 2020, König reported the umpolung reactivity of carbonyl compounds [10] via radical addition to N-sulfonylhydrazone followed by elimination of nitrogen and then quenched with electrophile in the presence of photo-redox catalysts and radical precursors, etc., summarized elsewhere. [11] Similar reaction was observed by Zeng group with N-sulfonylhydraones. [12] Recently, the Nöel group has also shown radical addition to Nsulfonylhydrazone in the presence of photocatalyst.…”

Light‐Induced Transformations of Donor‐Donor Diazo Compounds Derived from N‐Sulfonylhydrazones

“…The chemistry of N ‐sulfonylhydrazones has been widely explored under thermal conditions, either with/or without transition‐metal catalysts, and discussed in many reviews [3] . In 2020, König reported the umpolung reactivity of carbonyl compounds [10] via radical addition to N ‐sulfonylhydrazone followed by elimination of nitrogen and then quenched with electrophile in the presence of photo‐redox catalysts and radical precursors, etc., summarized elsewhere [11] . Similar reaction was observed by Zeng group with N ‐sulfonylhydraones [12] .…”

“…[3] In 2020, König reported the umpolung reactivity of carbonyl compounds [10] via radical addition to N-sulfonylhydrazone followed by elimination of nitrogen and then quenched with electrophile in the presence of photo-redox catalysts and radical precursors, etc., summarized elsewhere. [11] Similar reaction was observed by Zeng group with N-sulfonylhydraones. [12] Recently, the Nöel group has also shown radical addition to Nsulfonylhydrazone in the presence of photocatalyst.…”

Direct Deoxygenative Homocoupling of Alcohols to Access C(sp 3 )–C(sp 3 ) Bonds via Synergistic Ruthenium/Nickel Catalysis

“…Based on the above mechanistic studies and our previous studies, , a plausible mechanism for this transformation is proposed in Scheme . Initially, the ruthenium­(II) catalyst coordinates with the PNP iPr ligand to form complex A , which is converted into a highly reactive square planar complex B under the assistance of alkali .…”

Site-selective introduction of thiols in unprotected glycosides

“…46 The group of König reported that tosylhydrazones can be used in an umpolung difunctionalisation reaction with photoredox catalysis. 47,48 Although focusing on aromatic aldehydes as starting materials, also cyclic ketones were successfully explored and we expect that this approach can be adapted for the synthesis of thioethers. Currently, the chlorination of trityl hydrazone followed in situ by nucleophilic substitution of the chloride and subsequent thermolysis, is the only viable method for deoxy-thiolation in carbohydrates and therefore we continued by exploring its scope.…”

Light‐Induced Transformations of Donor‐Donor Diazo Compounds Derived from N‐Sulfonylhydrazones

“…The chemistry of N ‐sulfonylhydrazones has been widely explored under thermal conditions, either with/or without transition‐metal catalysts, and discussed in many reviews [3] . In 2020, König reported the umpolung reactivity of carbonyl compounds [10] via radical addition to N ‐sulfonylhydrazone followed by elimination of nitrogen and then quenched with electrophile in the presence of photo‐redox catalysts and radical precursors, etc., summarized elsewhere [11] . Similar reaction was observed by Zeng group with N ‐sulfonylhydraones [12] .…”

“…[3] In 2020, König reported the umpolung reactivity of carbonyl compounds [10] via radical addition to N-sulfonylhydrazone followed by elimination of nitrogen and then quenched with electrophile in the presence of photo-redox catalysts and radical precursors, etc., summarized elsewhere. [11] Similar reaction was observed by Zeng group with N-sulfonylhydraones. [12] Recently, the Nöel group has also shown radical addition to Nsulfonylhydrazone in the presence of photocatalyst.…”

Direct Deoxygenative Homocoupling of Alcohols to Access C(sp 3 )–C(sp 3 ) Bonds via Synergistic Ruthenium/Nickel Catalysis

“…Based on the above mechanistic studies and our previous studies, , a plausible mechanism for this transformation is proposed in Scheme . Initially, the ruthenium­(II) catalyst coordinates with the PNP iPr ligand to form complex A , which is converted into a highly reactive square planar complex B under the assistance of alkali .…”

Site-selective introduction of thiols in unprotected glycosides

“…46 The group of König reported that tosylhydrazones can be used in an umpolung difunctionalisation reaction with photoredox catalysis. 47,48 Although focusing on aromatic aldehydes as starting materials, also cyclic ketones were successfully explored and we expect that this approach can be adapted for the synthesis of thioethers. Currently, the chlorination of trityl hydrazone followed in situ by nucleophilic substitution of the chloride and subsequent thermolysis, is the only viable method for deoxy-thiolation in carbohydrates and therefore we continued by exploring its scope.…”

Light‐Induced Transformations of Donor‐Donor Diazo Compounds Derived from N‐Sulfonylhydrazones

“…The chemistry of N ‐sulfonylhydrazones has been widely explored under thermal conditions, either with/or without transition‐metal catalysts, and discussed in many reviews [3] . In 2020, König reported the umpolung reactivity of carbonyl compounds [10] via radical addition to N ‐sulfonylhydrazone followed by elimination of nitrogen and then quenched with electrophile in the presence of photo‐redox catalysts and radical precursors, etc., summarized elsewhere [11] . Similar reaction was observed by Zeng group with N ‐sulfonylhydraones [12] .…”

“…[3] In 2020, König reported the umpolung reactivity of carbonyl compounds [10] via radical addition to N-sulfonylhydrazone followed by elimination of nitrogen and then quenched with electrophile in the presence of photo-redox catalysts and radical precursors, etc., summarized elsewhere. [11] Similar reaction was observed by Zeng group with N-sulfonylhydraones. [12] Recently, the Nöel group has also shown radical addition to Nsulfonylhydrazone in the presence of photocatalyst.…”

Direct Deoxygenative Homocoupling of Alcohols to Access C(sp 3 )–C(sp 3 ) Bonds via Synergistic Ruthenium/Nickel Catalysis

“…Based on the above mechanistic studies and our previous studies, , a plausible mechanism for this transformation is proposed in Scheme . Initially, the ruthenium­(II) catalyst coordinates with the PNP iPr ligand to form complex A , which is converted into a highly reactive square planar complex B under the assistance of alkali .…”

Site-selective introduction of thiols in unprotected glycosides

“…46 The group of König reported that tosylhydrazones can be used in an umpolung difunctionalisation reaction with photoredox catalysis. 47,48 Although focusing on aromatic aldehydes as starting materials, also cyclic ketones were successfully explored and we expect that this approach can be adapted for the synthesis of thioethers. Currently, the chlorination of trityl hydrazone followed in situ by nucleophilic substitution of the chloride and subsequent thermolysis, is the only viable method for deoxy-thiolation in carbohydrates and therefore we continued by exploring its scope.…”