Iridium-Catalyzed C−C Coupling via Transfer Hydrogenation:  Carbonyl Addition from the Alcohol or Aldehyde Oxidation Level Employing 1,3-Cyclohexadiene

Abstract

Under hydrogen auto-transfer conditions employing a catalyst derived from [Ir(cod)Cl] 2 and BIPHEP, 1,3-cyclohexadiene (CHD) couples to benzylic alcohols 1a-9a to furnish carbonyl addition products 1c-9c, which appear as single diastereomers with variable quantities of regioisomeric adducts 1d-9d. Under related transfer hydrogenation conditions employing isopropanol as terminal reductant, identical carbonyl adducts 1c-9c are obtained from the aldehyde oxidation level. Isotopic labeling studies corroborate a mechanism involving hydrogen donation from the reactant alcohol or sacrificial alcohol (i-PrOH).As part of a broad program aimed at the development of methods for byproduct-free carbonyl and imine addition, 1,2 we recently reported that carbonyl allylation may be achieved by simply hydrogenating allenes in the presence of aldehydes. 2h Though effective for reverse prenylation, attempted crotylations and allylations using gaseous hydrogen as the terminal reductant suffered from over-reduction of the olefinic adduct. To address this limitation, allene-aldehyde reductive coupling was performed under the conditions of mkrische@mail.utexas.edu . Supporting Information Available. Experimental procedures and spectral data for all new compounds ( 1 H NMR, 13 C NMR, IR, HRMS). This material is available free of charge via the internet at http://pubs.acs.org. transfer hydrogenation using isopropanol as the terminal reductant. 2i In the course of these studies, it was found that carbonyl allylation could be achieved directly from the alcohol oxidation level by way of allene-alcohol transfer hydrogenation, 2i constituting a novel variant of hydrogen auto-transfer processes wherein hydrogen exchange between reactants is used to generate nucleophile-electrophile pairs (Scheme 1). 2i, 3,4,5,6,7 Through hydrogen auto-transfer, there exists the potential to develop a broad new family of byproduct-free catalytic C-C bond formations wherein alcohols and diverse π-unsaturated compounds are exploited as coupling partners. Motivated by this prospect, diene-aldehyde hydrogen auto-transfer was explored. Catalytic diene-aldehyde reductive coupling has been accomplished in both intra-and intermolecular settings. 8,9,10 Recently, the first examples of asymmetric diene-aldehyde intermolecular coupling were reported.9k,l Here, we disclose that 1,3-cyclohexadiene and aromatic alcohols 1a-9a engage in C-C coupling under the conditions of iridium catalyzed hydrogen auto-transfer. Additionally, we report the coupling of 1,3-cyclohexadiene to an analogous set of aldehydes 1b-9b under related transfer hydrogenation conditions employing isopropanol as the terminal reductant. NIH Public AccessInitial studies focused upon the coupling of benzyl alcohol 1a to 1,3-cyclohexadiene (CHD) under the conditions of iridium catalysis. It was found that a catalyst derived from commercially available [Ir(cod)Cl] 2 and BIPHEP delivers homoallylic alcohol 1c as a mixture of diastereomers, along with significant amounts of the regioisomeric product 1...

Metal-catalyzed reductive coupling of olefin-derived nucleophiles: Reinventing carbonyl addition

“…Related hydrohydroxymethylations that directly employ methanol (36 × 10 6 tons/year) as a coupling partner were reported for the first time using an iridium catalyst and 1,1-disubstituted allenes as pronucleophiles (33). Indeed, iridium complexes also catalyze the reaction of dienes with carbonyl compounds to form secondary homoallylic alcohols (33, 34). Cyclohexadiene (34) and butadiene (35) engage in either 2-propanol-mediated reductive coupling or, as shown, direct primary alcohol C-C coupling via hydrogen auto-transfer (Figure 6).…”

“…Indeed, iridium complexes also catalyze the reaction of dienes with carbonyl compounds to form secondary homoallylic alcohols (33, 34). Cyclohexadiene (34) and butadiene (35) engage in either 2-propanol-mediated reductive coupling or, as shown, direct primary alcohol C-C coupling via hydrogen auto-transfer (Figure 6). …”

Green chemistry for chemical synthesis

“…The processes of adding allyl alcohol to alkynes to form ␥,␦-unstaturated ketones and aldehydes in aqueous media were developed by Trost et al (14) and Dixneuf et al (15), respectively (Scheme 5). Another elegant example was recently reported by Krische and coworkers (16), in which primary alcohols were added stereoselectively to alkenes, which provides an atom-economic version of the classical reaction where a Grignard reagent is added to an aldehyde (Scheme 6).…”

Hydrogenation for C  C Bond Formation

“…Initial studies aimed at exploring the scope of such processes auger well for the generality of this novel approach to catalytic CÀC coupling [87]. For example, upon exposure to the neutral iridium precatalyst derived from [Ir(cod)Cl] 2 and BIPHEP, 1,3-cyclohexadiene couples readily to aldehydes under the conditions of transfer hydrogenation employing 2-propanol as terminal reductant.…”