Nickel‐Catalyzed α‐Allylation of Aldehydes and Tandem Aldol Condensation/Allylation Reaction with Allylic Alcohols

Abstract

An additive-free nickel-catalyzed α-allylation of aldehydes with allyl alcohol is reported. The reaction is promoted by 1 mol % of in situ formed nickel complex in methanol, and water is the sole by-product of the reaction. The experimental conditions allow the conversion of various α-branched aldehydes and α,β-unsaturated aldehydes as nucleophiles. The same catalyst and reaction conditions enabled a tandem aldol condensation of aldehyde/α-allylation reaction.

Efficient Access to All‐Carbon Quaternary and Tertiary α‐Functionalized Homoallyl‐type Aldehydes from Ketones

“…[1] From ar eactivity perspective,t he high electrophilicity of the aldehyde moiety represents an excellent tool for constructing sterically hindered quaternary centers.I nt his context, the a-allylation of aldehydes to generate the corresponding homoallyl derivatives has been extensively investigated (Scheme 1A1). [7] Interestingly,f or simple linear aldehydes,t his reaction could be incorporated into at andem aldol condensation/allylation process.The development of these strategies also allowed overcoming the reluctance of the conceptually simplest strategy based on the use of aldehyde enolates as nucleophiles in alkylation chemistry. [2] Fine-tuning of the reaction conditions enabled the development of highly enantioselective variants by the groups of List [3] and Yoshida, [4] which complement asymmetric organocatalytic (Jacobsen) [5] and stereodivergent dual-catalytic (Carreira) [6] approaches.T he process also benefits from switching to nickel catalysis,a sr ecently disclosed by Sauthier and coworkers.…”

“…The reactions proceeded cleanly and gave the corresponding products in high chemical yields regardless of the nature [cyclic (6)(7)(8)(9)(10)(11)(12)(13)(14)(15)oracyclic (3,16)] of the substrates and the substitution pattern across the starting ketones.W ea nticipated that our method would provide access to important a-methyl aldehydes (e.g., [8][9][10], which are used as substrates for ap lethora of chemical transformations, [25] in just one chemical operation, without the need for the multistep (four) and complex procedures routinely employed. The reactions proceeded cleanly and gave the corresponding products in high chemical yields regardless of the nature [cyclic (6)(7)(8)(9)(10)(11)(12)(13)(14)(15)oracyclic (3,16)] of the substrates and the substitution pattern across the starting ketones.W ea nticipated that our method would provide access to important a-methyl aldehydes (e.g., [8][9][10], which are used as substrates for ap lethora of chemical transformations, [25] in just one chemical operation, without the need for the multistep (four) and complex procedures routinely employed.…”

Catalytic C−C Bond Formation Using a Simple Nickel Precatalyst System: Base‐ and Activator‐Free Direct C‐Allylation by Alcohols and Amines

“…The use of allylic alcohols and amines in such processes represents a more atom‐economical transformation (since water or ammonia—in the case of primary allylamines—are the by‐products), but the lower reactivity of these substrates typically demands the presence of stoichiometric amounts of activators (often Brønsted or Lewis acids) . The ability of nickel complexes to mediate oxidative insertion into C−O and C−N bonds without the need for activating reagents has led to these catalysts being used in allylation using alcohols and amines; to date, the reported processes using alcohols have required Ni(COD) 2 , and (where mixtures are possible) often do not show selectivity for monoallylated products (Figure ) …”

“…The use of allylic alcohols and amines in such processes represents am ore atomeconomical transformation( since water or ammonia-in the case of primary allylamines-are the by-products), but the lowerr eactivity of these substrates typically demands the presence of stoichiometric amountso fa ctivators (often Brønsted or Lewis acids). [5,6] The abilityo fn ickel complexes to mediate oxidative insertion into CÀOa nd CÀNb onds withoutt he need for activating reagents has led to thesec atalysts being used in allylation using alcohols [7,8] and amines; [7b, 9, 10] to date, the reportedp rocesses using alcohols have required Ni(COD) 2 ,a nd (where mixtures are possible)o ften do not show selectivity for monoallylatedp roducts (Figure 1). [12] We commencedo ur study with two aims:t od evelop a nickel-catalysed method using allyl amines or alcohols which delivered monoallylated products selectively,a nd to devisea meanso fa ccessing the crucial Ni 0 catalysts from an inexpensive, air-stable precursor.W ec hose to use NiBr 2 ·3 H 2 O, one of the most inexpensive nickel salts, [13] as our nickel source, and elemental zinc as the reducing agent (due to its low toxicity compared to other metal reducing agents, such as manganese); as mentioned, key goals of our study were to reduce the amount of reducing agent to al ow level, and to avoid the use of ab ase in the reaction, thereby simplifying still further the process.…”

Stereoselective Construction of Halogenated Quaternary Carbon Centers by Brønsted Base Catalyzed [4+2] Cycloaddition of α‐Haloaldehydes

“…[1] During the past decades,avariety of catalytic modes for aldehyde activation, including (vinylogous) enamine activation, [2] iminium activation, [3] SOMO activation, [4] and NHC organocatalysis, [5] have been established (Scheme 1A). [7] The enantioselective coupling of aldehydes to electrophiles through the enolate pathway was surprisingly quite limited, [8] and we are unaware of reports describing this strategy for aldehydes with a-heteroatomic substituents. [6] To address this long-standing problem, we envisioned that using ac hiral Brønsted base to noncovalently activate as terically hindered aldehyde for deprotonation might be af easible solution.…”