Controlled Alcohol–Carbonyl Interconversion by Nickel Catalysis

Abstract

The ability to transform one functional group into another lies at the heart of organic chemistry. Such functional-group interconversions do not involve carbon-carbon bond-forming reactions and are thus seen as less efficient for the construction of complex molecules, however, these interconversions are often critical to "set up" a molecule for such a transformation. The oxidation of primary and secondary alcohols (1 and 3) to produce aldehydes (2) and ketones (4) prior to the addition of organometallic species is a prime example (Scheme 1). Although this reaction is often essential for the subsequent carbon-carbon bond-forming transformation, it does add an extra, linear step to the sequence. Thus, we imagined that performing the two steps, oxidation and addition, together would greatly simplify synthetic routes by essentially eliminating the need to carry out a preliminary oxidation before converting, for example, a primary alcohol (1) into a secondary alcohol (3), or similarly 3 into a tertiary alcohol (5).Numerous practical advantages are associated with such one-pot multistep alcohol-carbonyl interconversions, [1] but a uniform methodology has not been developed, partly because of the incompatibility of the reaction conditions. Whereas alcohol-to-carbonyl transformations are oxidative, the reverse processes such as carbonyl addition reactions are reductive in nature. Herein, we report that [Ni(cod) 2 ]/IPr (cod = 1,5-cyclooctadiene, IPr = 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene) serves as a general catalyst for the controlled one-pot oxidation-addition of alcohols and carbonyl compounds. We demonstrate the feasibility of all possible multistep transformations in alcohol-carbonyl interconversions (Scheme 1). A one-pot nickel-catalyzed synthesis of flumecinol (a hepatic microsomal enzyme inducer) is also described.As an important progress toward controlled carbonylalcohol interconversions, we recently established that the [Ni(cod) 2 ]/IPr catalyst promotes the otherwise difficult intermolecular 1,2-addition of arylboronate esters to unactivated ketones and aldehydes.[2] Among the various arylboron reagents screened, arylboronic acid neopentyl glycol ester ArB(neo) turned out to be the most reactive. The advantage of our [Ni-IPr] catalytic system [2] over other transition-metalcatalyzed organoboron-based 1,2-additions is obvious from the viewpoint of the substrate scope. While other catalytic systems are generally only applicable to aldehydes [3] and some electronically and strain-activated ketones, [4] our [Ni-IPr] catalysis shows good reactivity not only toward aldehydes but also toward diaryl, alkyl aryl, and dialkyl ketones under mild reaction conditions.[2] The high reactivity of our [Ni-IPr] catalyst might be partly due to the unique Ni 0 /Ni II mechanism (right-hand catalytic cycle, Scheme 2).Since many transition-metal complexes are able to mediate the oxidation of alcohols to aldehydes or ketones, [5] we envisioned that our nickel catalysis could be extended to a controlled alcohol-carbonyl i...

Nickel-catalyzed Cycloaddition of Aromatic (O-Benzyl)ketoximes with Alkynes to Produce Isoquinoline and Isoquinoline N-Oxide Derivatives

“…Even though we were not successful in an isolation of the nickelacycle intermediate, we found that treatment of 1a with stoichiometric amount of Ni(0)/dppf in the absence of alkyne furnished benzyl alcohol. 12 The alkyne would then insert into the CNi bond to give seven-membered nickelacycle. With its seven-membered ring strain, Ni can undergo a facile reductive elimination to give 3aa, and regenerates the starting Ni(0) complex.…”

Introducing Glycerol as a Sustainable Solvent to Organolithium Chemistry: Ultrafast Chemoselective Addition of Aryllithium Reagents to Nitriles under Air and at Ambient Temperature

“…The identity of obtained tertiary alcohols 4a, [29] 4b [30] and 4c [31] was assessed by comparison of their 1 Ha nd 13 CNMR spectroscopic data with those reported in the literature. In ag lass tube, the appropriate ketone (0.5 mmol) was dissolved in glycerol (0.5 g) under air,t ow hich PhLi (1 mmol) was added at room temperature, and the reaction mixture was stirred for 2-3 s. The reaction was then stopped by addition of as aturated solution of the Rochelle salt (sodium potassium tartrate tetrahydrate) and organic products were extracted with dichloromethane (3 5mL).…”

“…Yields of the reaction crudes were determined by 1 H NMR spectroscopy by using dibromomethane as an internal standard. The identity of obtained tertiary alcohols 4 a , 4 b and 4 c was assessed by comparison of their 1 H and 13 C NMR spectroscopic data with those reported in the literature.…”

Access to the most sterically crowded anilines via non-catalysed C–C coupling reactions

“…Similarly, the signals of the hydroxy groups in 1a-c were also shifted downfield with respect to analogous Ph 3 COH (2.78 ppm), indicating the presence of OHÁ Á ÁN hydrogen bonding. 18 Despite the diversity of the substituents on the benzhydryl moieties, the molecular structures of 1a-4a, 1b-4b and 4c are analogous (see Fig. 2 and 3 for examples; for further information, see the ESI †).…”