Quaternary Carbon Stereogenic Centers through Copper‐Catalyzed Enantioselective Allylic Substitutions with Readily Accessible Aryl‐ or Heteroaryllithium Reagents and Aluminum Chlorides

Abstract

The case of the notorious aryls is solved: The first efficient catalytic and enantioselective method for allylic substitutions that furnish quaternary carbon stereogenic centers by additions of aryl‐ or heteroarylmetals is reported (see scheme). Highly site‐ and enantioselective processes begin with readily available organolithium reagents.

Exceptionally E‐ and β‐Selective NHC–Cu‐Catalyzed Proto‐Silyl Additions to Terminal Alkynes and Site‐ and Enantioselective Proto‐Boryl Additions to the Resulting Vinylsilanes: Synthesis of Enantiomerically Enriched Vicinal and Geminal Borosilanes

“…(1)] 36. Adoption of the reported procedures would be less attractive, as they would require the use of di(benzyl)zinc or tri(benzyl)aluminum reagents, preparation of which is less than straightforward; if di(alkyl)benzylaluminum species are employed,37 a mixture of benzyl and alkyl addition products would likely be obtained …”

Synthesis and Applications in Catalysis of Metal Complexes with Chelating Phosphinosulfonate Ligands

“…101,102 A proposed mechanistic model accounting for the enantioselective transformation was proposed by the authors where the sulfonate and phosphate moieties coordinate to diisobutyl aluminium cation in the anionic copper(I) intermediate (Fig. 103 The use of alkynyl(diisobutyl)aluminiums provided a straightforward access not only to chiral 1,4-enynes 104 but also to chiral allenes after treatment of the formed 1,4-enynes featuring tertiary stereogenic center in the presence of DBU. 103 The use of alkynyl(diisobutyl)aluminiums provided a straightforward access not only to chiral 1,4-enynes 104 but also to chiral allenes after treatment of the formed 1,4-enynes featuring tertiary stereogenic center in the presence of DBU.…”

Enantioselective Synthesis of Quaternary Carbon Stereogenic Centers through Copper‐Catalyzed Conjugate Additions of Aryl‐ and Alkylaluminum Reagents to Acyclic Trisubstituted Enones

“…Catalytic ECA of acyclic enones to afford all-carbon quaternary stereogenic centers can be applied to the total synthesis of biologically active molecule and/or facilitate the elucidation of their absolute stereochemical identity. that, although efficient catalytic enantioselective allylic substitutions (EAS) with the same types of organoaluminum reagents have been reported, [13] ECA processes present a distinct challenge for several reasons. In both cases, nucleophilic addition of an organocopper intermediate is likely followed by reductive elimination; the first key step, however, is reversible only in ECA, requiring CÀC bond formation to be sufficiently rapid.…”

“…Reaction is complete in 12 h at À30 8C without generating any detectable amount of byproducts derived from Me transfer. [13] As further depicted in Scheme 2, we evaluated the possibility of performing an enantioselective ECA with the corresponding thienyl-aluminum reagent and phenyl-substituted a,b-unsaturated ketone 2 b. Under the latter conditions, the transformation proceeds to complete conversion in 12 h, affording (S)-3 a in 80 % yield and > 99:1 e.r.…”

“…[16] The NHC-Cu complex derived from 1, which emerged as the superior choice, has not been previously employed. [13] A range of trisubstituted enones and in situ generated aryl(dialkyl)aluminum reagents can be used (Table 1). Reaction involving 2-thienyl-substituted 2 c (vs. 3-substituted 2 a, Scheme 2) with Ph(Me) 2 Al leads to 73 % conversion in 12 h (entry 1), and 3 b is isolated in 57 % yield with complete transfer of the phenyl unit in 92:8 e.r.…”