Catalyst, additive and counterion effects on the efficiency and enantioselectivity of copper-catalysed C–H insertion reactions of α-diazosulfones

Enantioselective copper catalysed intramolecular C–H insertion reactions of α-diazo-β-keto sulfones, α-diazo-β-keto phosphine oxides and 2-diazo-1,3-diketones; the influence of the carbene substituent

“…1,2 Previous studies from our laboratory have shown that the use of a copper catalyst system comprised of copper-bis(oxazoline)-NaBARF is very effective in inducing high levels of enantiocontrol in C-H insertions of α-diazocarbonyl compounds bearing arylsulfonyl substituents. Thiopyrans 1, cyclopentanones 2 and γ-lactams 3 have been synthesised in excellent enantioselectivities of up to 98 %ee, 22 89 %ee 24 and 78 %ee 25 respectively (Scheme 2). The presence of the additive NaBARF was found to be essential for achieving high levels of asymmetric induction, 24,26 through abstraction of chloride by the sodium cation of NaBARF, thereby altering the catalyst geometry as Fraile has previously discussed.…”

“…Thiopyrans 1, cyclopentanones 2 and γ-lactams 3 have been synthesised in excellent enantioselectivities of up to 98 %ee, 22 89 %ee 24 and 78 %ee 25 respectively (Scheme 2). The presence of the additive NaBARF was found to be essential for achieving high levels of asymmetric induction, 24,26 through abstraction of chloride by the sodium cation of NaBARF, thereby altering the catalyst geometry as Fraile has previously discussed. 27,28 Scheme 2 Copper catalysed C-H insertion reactions of α-diazo-β-keto sulfones, α-diazo-β-oxo sulfones and α-diazoacetamides.…”

Enantioselective carbenoid insertion into C(sp3)–H bonds

“…This research group has focused a lot of efforts to better comprehend the scope of this catalytic system, especially on features concerning the BARF salt effect [ 43 – 44 ] and electronic effects on the aromatic rings of the chiral ligands [ 45 ].…”

Stereoselective radical C–H alkylation with acceptor/acceptor-substituted diazo reagents via Co(ii)-based metalloradical catalysis

“…Among previous efforts toward enantioselective C–H alkylation with A/A-substituted diazo reagents, 7 the most notable example is the Cu-based intramolecular system recently reported by Maguire and coworkers. 8 Supported by chiral bisoxazoline ligands, this Cu-catalyzed asymmetric system was shown to enable intramolecular C–H insertion with α-alkoxycarbonyl-α-diazosulfones, affording the corresponding six-membered thiopyrans in high enantioselectivities. 8 However, the yields of the desired products were generally low to moderate (30–68%) as the Cu-catalyzed reactions typically gave a complex mixture of products.…”

“… 8 Supported by chiral bisoxazoline ligands, this Cu-catalyzed asymmetric system was shown to enable intramolecular C–H insertion with α-alkoxycarbonyl-α-diazosulfones, affording the corresponding six-membered thiopyrans in high enantioselectivities. 8 However, the yields of the desired products were generally low to moderate (30–68%) as the Cu-catalyzed reactions typically gave a complex mixture of products. Furthermore, it was reported that the efficiency of the catalytic system was further reduced for C–H substrates with decreased electron richness.…”