By using commercially available 1,4-pentadiene
as a pronucleophile,
a copper(I)-catalyzed regioselective asymmetric allylation of ketones
is achieved. A variety of chiral tertiary alcohols bearing a terminal
(Z)-1,3-diene unit are generated in high (Z)/(E) ratio and high enantioselectivity.
Both aromatic ketones and aliphatic ketones serve as suitable substrates.
Furthermore, the reactions with (E)-C1(alkyl)-1,4-dienes proceed in moderate yields with acceptable enantioselectivity
but with low (Z,E)/others ratio,
which demonstrates the partial isomerization of (E)-allylcopper(I) species to (Z)-allylcopper(I) species
through 1,3-migration. Subsequent Heck reaction and olefin metathesis
compensate for the low efficiency with C1-1,4-dienes. The
synthetic utility of the product is further demonstrated by a copper(I)-catalyzed
regioselective borylation of the 1,3-diene group.
Catalytic asymmetric conjugate allylation of unsaturated carbonyl compounds is usually difficult to achieve, as 1,2-addition proceeds dominantly and high asymmetric induction is a challenging task. Herein, we disclose a copper(I)-NHC complex catalyzed asymmetric 1,6-conjugate allylation of 2,2-dimethyl-6-alkenyl-4H-1,3-dioxin-4-ones. The phenolic hydroxyl group in NHC ligands is found to be pivotal to obtain the desired products. Both aryl group and alkyl group at δ-position are well tolerated with the corresponding products generated in moderate to high yields and high enantioselectivity. Moreover, both 2-substituted and 3-substituted allylboronates serve as acceptable allylation reagents. At last, the synthetic utility of the products is demonstrated in several transformations by means of the versatile terminal olefin and dioxinone groups.
Chiral azaarene compounds are extremely important due
to their
prevalence in pharmaceutical ingredients. Herein, an array of chiral
molecules bearing azaaryl groups is synthesized in moderate-to-excellent
yields with moderate-to-excellent Z/E ratios, high dr, and excellent enantioselectivity by a copper(I)-catalyzed
asymmetric conjugate addition of 1,4-dienes to (E)-β-substituted alkenyl azaarenes. The reaction is carried
out under mild proton-transfer conditions, which enjoys very high
atom economy. Moreover, the reaction features a broad substrate scope
on (E)-α,β-unsaturated azaarenes as various
azaarenes are well tolerated, such as benzothiazole, thiazole, N-methyl-benzimidazole, benzoxazole, quinoline, isoquinoline,
pyrimidine, pyrazine, and triazine. Interestingly, the reaction with
(Z)-α,β-unsaturated azaarenes affords
the same products in excellent results but with a reversed absolute
configuration. DFT calculations indicate that the C–C bond-forming
nucleophilic addition is a Z-/E-
and enantio-selectivities-determining step and provides a rationale
for the origin of selectivities. At last, the synthetic utilities
of the product are showcased by several transformations, including
olefin metathesis, [4 + 2] cyclization, [2 + 1] cyclization, and cleavage
of the benzothiazole ring.
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