The effective use of ring strain has been applied to considerable advantage for the construction of complex systems. The focus here is directed towards cyclopropanes as building blocks for organic synthesis. Although thermodynamics should take the side of synthetic chemists, only a specific substitution pattern at the cyclopropane ring allows for particularly mild, efficient, and selective transformations. The required decrease in the activation barrier is achieved by the combined effects of vicinal electron-donating and electron-accepting moieties. This Review highlights the appropriate tools for successfully employing donor–acceptor cyclopropanes in ring-opening reactions, cycloadditions, and rearrangements.

A new golden age for donor-acceptor cyclopropanes.

Selective cleavages of carbon-carbon bonds catalyzed by transition-metal complexes have been shown to be increasingly versatile tools for organic synthesis allowing for complementary synthetic strategies Numerous examples of transition-metal catalyzed C-C bond activations of three- and four-membered ring systems have been reported These strained rings have been shown to engage in a variety of new ring-opening rearrangements and cycloaddition reactions leading to valuable structures Besides strain-driven transformations, other facilitating strategies to enforce the C-C bond activation of unstrained molecules have been developed as well While the variety of different transformations is less abundant, they concentrate on chelation-assisted reactions using appropriate permanent or transient directing groups In particular, the cleavage and subsequent functionalization of the C-CN bonds and decarbonylation processes operating by an excision of carbon monoxide from ketone derivatives have witnessed a large progress

Catalytic C-C Bond Activations via Oxidative Addition to Transition Metals.

In this review, synthetic and mechanistic aspects of key methodologies that exploit C–C single-bond cleavage of strained ring systems are highlighted. The focus is on transition-metal-catalyzed processes that are triggered by C–C bond activation and β-carbon elimination, with the review concentrating on developments from mid-2009 to mid-2016.

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Recent Methodologies That Exploit C-C Single-Bond Cleavage of Strained Ring Systems by Transition Metal Complexes

This review summarizes research directed towards the formation of carbocyclic adducts from donor–acceptor cyclopropanes. The focus of the review is on annulation and cycloaddition reactions (both inter- and intramolecularly) mediated by Lewis or protic acid, bases, or thermal conditions. Rearrangements resulting in carbocycles and those reactions mediated by transition metal catalysis have been excluded.

Carbocycles from donor–acceptor cyclopropanes

As organic molecules are defined as compounds composed of carbon and hydrogen, stereoselective, atom-efficient methods for skeletal assembly involving the addition, removal or redistribution of hydrogen in the absence of discrete oxidation level adjustment, or non-constructive functional group interconversions represent a natural endpoint in the evolution of synthetic methods.[1] This view of synthetic efficiency tacitly recognizes the value of merged redox-construction events (“redox-economy”),[2] chemo- (site-), regio- and stereoselectivity,[3] protecting group-free chemical synthesis,[4] as well as the minimization of preactivation, defined as the degree of separation between reagent and feedstock.[5] Transformations and strategies that adhere to these ideals are inherently process-relevant.[6]

Application of these concepts to the chemistry of carbonyl addition reveals a significant opportunity for invention. In classical carbonyl additions, premetallated C-nucleophiles and carbonyl compounds are typically generated through separate streams of redox reactions: discrete alcohol-to-aldehyde oxidation is frequently used to generate carbonyl electrophiles, and discrete reduction is often used to generate organometallic nucleophiles. By exploiting the native reducing capability of alcohols, redox-triggered carbonyl additions may be developed wherein hydrogen exchange between alcohols and unsaturated reactants generates transient electrophile- nucleophile pairs en route to products of formal alcohol C-H functionalization via carbonyl addition.[7] To date, three major mechanistic pathways for C-C coupling have been identified wherein alcohol oxidation is balanced by (A) C=C π-bond hydrometallation, (B) C-X reductive cleavage, and (C) transfer hydrogenolysis of oxametallacycles (Figure 1).



Figure 1

Redox-economy in carbonyl addition: three general mechanistic pathways identified for redox-triggered alcohol C-H functionalization.



In this review, catalytic enantioselective methods for C-C bond formation via alcohol CH functionalization are surveyed on the basis of the aforementioned mechanistic pathways. Related redox-triggered alcohol C-H functionalizations that have not been rendered asymmetric are covered elsewhere,[7] For most alcohol C-C couplings described in this account, corresponding aldehyde reductive couplings are reported,[7] but for the sake of brevity are not covered. Dehydrogenative C-C bond formations that result in formal alcohol substitution, that is, so-called “borrowing hydrogen” or “hydrogen auto-transfer” processes, radical mediated alcohol C-C couplings and processes involving stoichiometric oxidants are not discussed.[8,9]

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Catalytic enantioselective C-H functionalization of alcohols by redox-triggered carbonyl addition: Borrowing hydrogen, returning carbon

The coupling of carbonyl electrophiles at the donor position of donor–acceptor cyclopropanes is described, representing an inversion of polarity with respect to conventional reactivity modes displayed by these reagents. Specifically, upon exposure of donor–acceptor cyclopropanes to alcohols in the presence of a cyclometalated iridium catalyst modified by (S)-BINAP, catalytic C–C coupling occurs, providing enantiomerically enriched products of carbonyl allylation. Identical products are obtained upon isopropanol-mediated transfer hydrogenation of donor–acceptor cyclopropanes in the presence of aldehydes. The reaction products are directly transformed to cis-4,5-disubstituted δ-lactones.

/pdf/polarity-inversion-of-donor-acceptor-cyclopropanes-2bnagrpw4m.pdf

Polarity inversion of donor-acceptor cyclopropanes: disubstituted δ-lactones via enantioselective iridium catalysis.

https://pubs.acs.org/doi/pdf/10.1021/ol500256n

Lewis acid catalyzed (3 + 2)-annulations of donor-acceptor cyclopropanes and ynamides.

In the presence of IRC, the donor—acceptor cyclopropanes (I) and (VI) undergo polarity inversion and react with alcohols and aldehydes to afford hydroxycarboxylic acid esters of type (III)/(VII).

Polarity Inversion of Donor—Acceptor Cyclopropanes: Disubstituted δ‐Lactones via Enantioselective Iridium Catalysis.

N,N-Dimethylaniline as well as 4-chlorophenyl substituted cyclopropane analogues fail to react.

Ryan M. Carris

Papers

Polarity inversion of donor-acceptor cyclopropanes: disubstituted δ-lactones via enantioselective iridium catalysis.

Lewis acid catalyzed (3 + 2)-annulations of donor-acceptor cyclopropanes and ynamides.

Polarity Inversion of Donor—Acceptor Cyclopropanes: Disubstituted δ‐Lactones via Enantioselective Iridium Catalysis.

Lewis Acid Catalyzed [3 + 2]‐Annulations of Donor—Acceptor Cyclopropanes and Ynamides.