Cobalt-Catalyzed Asymmetric 1,6-Addition of (Triisopropylsilyl)-acetylene to α,β,γ,δ-Unsaturated Carbonyl Compounds

et al. 2019

Angew Chem Int Ed

Racemic vinylallenes are shown to be effective substrates for catalytic multicomponent diastereo‐ and enantioselective 1,6‐conjugate addition of multifunctional allyl moieties to easily accessible α,β,γ,δ‐unsaturated diesters. Reactions may be catalyzed by 5.0 mol % of a readily accessible NHC‐Cu complex at ambient temperature, and other than a vinylallene, involve B2(pin)2 and an α,β,γ,δ‐unsaturated diester. A variety of vinylallenes were converted to products bearing a Z‐trisubstituted alkenyl‐B(pin) moiety, a vinyl group, a β,γ‐unsaturated diester unit, and vicinal stereogenic centers in up to 67 % yield, 87:13 Z/E ratio, >98:2 d.r., and 98:2 e.r. Chemoselective modifications involving the alkenyl‐B(pin), the vinyl, or the 1,2‐disubstituted olefin moieties were carried out to demonstrate versatility and utility. Stereochemical models, based on mechanistic and DFT studies, demonstrate the dynamic behavior of intermediated Cu‐allyl species and account for various selectivity profiles.

Section: Methodsmentioning

confidence: 99%

“…These advances, while notable, were confined to magnesium‐, Al‐, or Zn‐based entities containing a simple alkyl unit. Reactions with a silyl‐protected alkyne or an aryl moiety broadened the scope, but just one aryl group in a (ArBO) 3 compound could be transferred…”

Section: Methodsmentioning

confidence: 99%

Racemic Vinylallenes in Catalytic Enantioselective Multicomponent Processes: Rapid Generation of Complexity through 1,6‐Conjugate Additions

Huang

et al. 2019

Angew Chem Int Ed

“…However, catalytic enantioselective 1,6-conjugate additions are uncommon, and ones that are able to incorporate readily functionalizable moieties, such as propargyl or allyl groups, into acyclic α,β,γ,δ-doubly unsaturated acceptors are unknown 2 . Chemical transformations that could generate a new bond at the C6 position of a dienoate are particularly desirable, as the resulting products would be subjected to further modifications; such reactions, especially when dienoates contain two equally substituted olefins, are scarce 3 and are confined to reactions promoted by a phosphine–copper (with alkyl Grignard 4,5 , dialkylzinc or trialkylaluminum compounds 6,7 ), a diene–iridium (with arylboroxines) 8,9 , and a bisphosphine–cobalt catalyst (with monosilyl-acetylenes) 10 . 1,6-conjugate additions are otherwise limited to substrates where there is full substitution at C4 11 .…”

mentioning

confidence: 99%

Catalytic enantioselective 1,6-conjugate additions of propargyl and allyl groups

Meng

et al. 2016

Nature

123

Conjugate (or 1,4-) additions of carbanionic species to α,β-unsaturated carbonyl compounds are vital to research in organic and medicinal chemistry, and there are several known chiral catalysts that facilitate the catalytic enantioselective additions of nucleophiles to enoates1. However, catalytic enantioselective 1,6-conjugate additions are uncommon, and ones that are able to incorporate readily functionalizable moieties, such as propargyl or allyl groups, into acyclic α,β,γ,δ-doubly unsaturated acceptors are unknown2. Chemical transformations that could generate a new bond at the C6 position of a dienoate are particularly desirable, as the resulting products would be subjected to further modifications; such reactions, especially when dienoates contain two equally substituted olefins, are scarce3 and are confined to reactions promoted by a phosphine–copper (with alkyl Grignard4,5, dialkylzinc or trialkylaluminum compounds6,7), a diene–iridium (with arylboroxines)8,9, and a bisphosphine–cobalt catalyst (with monosilyl-acetylenes)10. 1,6-conjugate additions are otherwise limited to substrates where there is full substitution at C411. It is not clear why certain catalysts favor bond formation at C6, and – while there are a small number of catalytic enantioselective conjugate allyl additions12,13,14,15 – related 1,6-additions and processes involving a propargyl unit are non-existent. In this manuscript, we show that an easily accessible organocopper catalyst can promote 1,6-conjugate additions of propargyl and 2-boryl-substituted allyl groups to acyclic dienoates with high selectivity. A commercially available allenylboron compound or a monosubstituted allene may be used. Products can be obtained in up to 83 percent yield, >98 percent diastereo- (for allyl additions) and 99:1 enantiomeric ratio. Mechanistic details, including the origins of high site- (1,6- versus 1,4-) and enantioselectivity as a function of the catalyst structure and reaction type, have been elucidated by means of density functional theory (DFT) calculations.

“…reasons.U nlike catalytic 1,4-conjugate additions,f or which there are many enantioselective methods, [8] 1,6-conjugate additions involving carbon-based nucleophiles are rare, [9] especially with C4 not fully substituted. Theo nly known instances are those of Feringa, [10] Hayashi, [11,12] Alexakis. [13] These advances,while notable,were confined to magnesium-, [10] Al-, or Zn-based [13] entities containing asimple alkyl unit.…”

mentioning

confidence: 99%

“…[13] These advances,while notable,were confined to magnesium-, [10] Al-, or Zn-based [13] entities containing asimple alkyl unit. Reactions with as ilyl-protected alkyne [11] or an aryl moiety broadened the scope,b ut just one aryl group in a( ArBO) 3 compound could be transferred. [12] We surmised that the Cu-B(pin) complex would add regioselectively to av inylallene to generate II via I (Scheme 1).…”

mentioning

confidence: 99%

Racemic Vinylallenes in Catalytic Enantioselective Multicomponent Processes: Rapid Generation of Complexity through 1,6‐Conjugate Additions

Huang

et al. 2019

Angewandte Chemie

Racemic vinylallenes are shown to be effective substrates for catalytic multicomponent diastereo-and enantioselective 1,6-conjugate addition of multifunctional allyl moieties to easily accessible a,b,g,d-unsaturated diesters. Reactions may be catalyzedb y5 .0 mol %o fareadily accessible NHC-Cu complex at ambient temperature,and other than av inylallene,i nvolve B 2 (pin) 2 and an a,b,g,d-unsaturated diester.Avariety of vinylallenes were converted to products bearing aZ-trisubstituted alkenyl-B(pin) moiety,avinyl group, a b,g-unsaturated diester unit, and vicinal stereogenic centers in up to 67 %y ield, 87:13 Z/E ratio, > 98:2 d.r., and 98:2 e.r. Chemoselective modifications involving the alkenyl-B(pin), the vinyl, or the 1,2-disubstituted olefin moieties were carried out to demonstrate versatility and utility.S tereochemical models,b ased on mechanistic and DFT studies,d emonstrate the dynamic behavior of intermediated Cu-allyl species and account for various selectivity profiles. reasons.U nlike catalytic 1,4-conjugate additions,f or which there are many enantioselective methods, [8] 1,6-conjugate additions involving carbon-based nucleophiles are rare, [9] especially with C4 not fully substituted. Theo nly known instances are those of Feringa, [10] Hayashi, [11,12] Alexakis. [13] These advances,while notable,were confined to magnesium-, [10] Al-, or Zn-based [13] entities containing asimple alkyl unit. Reactions with as ilyl-protected alkyne [11] or an aryl moiety broadened the scope,b ut just one aryl group in a( ArBO) 3 compound could be transferred. [12] We surmised that the Cu-B(pin) complex would add regioselectively to av inylallene to generate II via I (Scheme 1). Although the vinyl site is less hindered, interaction between an allene bond, bearing an sp-and an sp 2hybridized carbon (vs.two sp 2 -hybridized vinyl carbons), and the Cu-B(pin) bond, where probably the HOMO is centered, [14] would be preferred. TheC u-allyl species II could isomerize to III,t he reaction of which with an a,b,g,dunsaturated diester would afford IV.T he intermediacyo fIII would mean that racemic vinylallene may be used (i.e., enantioselective synthesis vs.k inetic resolution).We began by probing reactions involving 1a,B 2 (pin) 2 and vinylallene 2a (Scheme 2). With chiral phosphine ligands there was complete consumption of 1a but no 3a was detected. [15] With imid-1 a, [16] optimal for previously reported reactions with monosubstituted allenes, [1e] 1,4-conjugate boryl addition was the main competing pathway; [17] 3a was isolated in just 21 %y ield and with 75:25 Z/E selectivity, > 98:2 diastereomeric ratio (d.r.), and 83:17 enantiomeric ratio (e.r.). These early findings underscored the distinct nature of the Scheme 1. General strategy pursued in this study.G ,R= carbon-based substituents;p in = pinacolato;L= ligand.Scheme 6. Stereochemical models accounting for the various stereoselectivity issues.