Well‐Defined and Robust Rhodium Catalysts for the Hydroacylation of Terminal and Internal Alkenes

Abstract

AR h-catalyst system based on the asymmetric ligand t Bu 2 PCH 2 P(o-C 6 H 4 OMe) 2 is reported that allows for the hydroacylation of challenging internal alkenes with bsubstituted aldehydes.Mechanistic studies point to the stabilizing role of both excess alkene and the OMe-group.The catalytic hydroacylation reaction between an aldehyde and an olefin (or carbonyl group such as ak etone) is an attractive atom-efficient route to ketones (or esters). [1] Preeminent are transition metal catalysts based on cationic [Rh(bidentate phosphine)]+ although other catalyst systems are known. [2] Irreversible reductive decarbonylation that arises from ac oordinatively unsaturated acyl-hydride intermediate (Scheme 1), [3] removes catalyst from the system competitively with productive turnover,w ith the result that early studies used high catalyst loadings (5-10 mol %) and relatively activated substrates.[4] Control of decarbonylation can come from substrate chelation, such as b-substituted aldehydes or alkenes, [1a, 5] whereas the use of the hemilabile ligand bis-[2-(diphenylphosphino)phenyl]ether (DPEphos) that reversibly binds to the vacant site through aRh···O linkage (Scheme 2), affords al ong-lived catalyst, but activity is not significantly enhanced resulting in ar ather limited scope of substrates. [6] An alternative approach is to increase the rate of reductive elimination of ketone product, as tep that is often (although not exclusively [7] )t he turnover-limiting process in hydroacylation. [3a,8] Wide-bite-angle,o rs terically bulky,l igands have this effect, but also change the ratio of alkene versus aldehyde hydroacylation [9] or the linear/branched selectivity.[10] Additionally,these systems in general still require high loadings,a nd activated alkenes or terminal alkynes as substrates.S mall-bite-angle phosphine ligands,R 2 PCH 2 PR 2 (e.g.,R= t Bu, Cy), initially developed by Hofmann et al., [11] have been shown to favor the products of reductive elimination [12] and we recently demonstrated that catalyst systems exemplified by [Rh(R 2 PCH 2 PR 2 )(h 6 -C 6 H 5 F)][BAr F 4 ][ R = t Bu, 1;A r F = 3,5-C 6 H 3 (CF 3 ) 2 ]c an be used at low catalyst loadings (e.g., 0.1 mol %) to couple terminal and activated internal alkenes with b-substituted aldehydes.[13] However, challenging internal alkenes are still out of reach with this system, as decarbonylation now outruns productive turnover. Others have since used similar ligands for intermolecular hydroacylation. [5b,7c] Small-bite-angle diphosphine ligands have also been used in alkene oligomerization reactions,i nw hich reductive elimination is proposed to play ak ey role in determining selectivity.[14] Those with a" P(o-C 6 H 4 OMe) 2 "m otif are particularly active,a nd solid-state structures indicate that the OMe group can interact with the metal center,a lthough whether this leads to enhanced selectivity is yet to be delineated. [15] We thus speculated whether such am otif might offer improved catalyst turnover and/or stability for hydroacyl...

Acyl Glycosides through Stereospecific Glycosyl Cross-Coupling: Rapid Access to C(sp3)-Linked Glycomimetics

“…11,29 These indirect protocols are plagued by a competitive glycal formation. 29 Other methods toward C-acyl glycosides involve benzothiazole manipulations, 30 vinylation and oxidative cleavage of the olefins, 31 hydroacylation of glycals, 32 and reactions involving C1 organolithium intermediates 33,34 but require additional synthetic steps to afford glycosyl ketones. Despite these recent advancements, the absence of a general and predictable method for stereospecific anomeric acylation remains a major methodological gap preventing greater investigation into the biology and applications of these compounds as viable precursors to C(sp 3 ) glycomimetics.…”