Abstract:A rhodium-catalyzed conjugate alkynylation/aldol cyclization cascade was developed. Densely functionalized cyclic α-propargyl-β-hydroxyketones were synthesized with simultaneous formation of a C(sp)-C(sp) bond, a C(sp)-C(sp) bond, as well as three new contiguous stereocenters. The transformation was achieved with excellent enantio- and diastereoselectivities using BINAP as the ligand. The synthetic utility of the newly installed alkynyl moiety was exhibited by subjecting the products to an array of derivatizat… Show more
“…These ring closures lead to densely functionalized cyclopentanes and -hexanes with three or four contiguous stereocenters. Various diastereotopic group-selective aldol reactions have already been described, including copper-catalyzed addition of hydride , and boron and carbon nucleophiles , (Scheme , bottom) . We now disclose here a cyclization of this system initiated by conjugate silylation where the choice of the zinc- or boron-based − silicon (pro)nucleophile determines the relative configuration of the bicyclic product (Scheme , bottom) …”
A reaction sequence
consisting of enantioselective copper-catalyzed
conjugate silylation and diastereotopic group-selective aldol cyclization
is reported. The diastereoselectivity of the intramolecular aldol
reaction depends on the silicon nucleophile used, either Me2PhSiZnX·2LiX (trans) or Me2PhSiBpin (cis). The more
basic zinc reagent and as such the very basic reaction medium also
enable thermodynamically driven cis-to-trans isomerization by a retro-aldol–aldol
process. A broad range of electron-withdrawing groups including electron-deficient
heterocycles is compatible with the different procedures developed.
“…These ring closures lead to densely functionalized cyclopentanes and -hexanes with three or four contiguous stereocenters. Various diastereotopic group-selective aldol reactions have already been described, including copper-catalyzed addition of hydride , and boron and carbon nucleophiles , (Scheme , bottom) . We now disclose here a cyclization of this system initiated by conjugate silylation where the choice of the zinc- or boron-based − silicon (pro)nucleophile determines the relative configuration of the bicyclic product (Scheme , bottom) …”
A reaction sequence
consisting of enantioselective copper-catalyzed
conjugate silylation and diastereotopic group-selective aldol cyclization
is reported. The diastereoselectivity of the intramolecular aldol
reaction depends on the silicon nucleophile used, either Me2PhSiZnX·2LiX (trans) or Me2PhSiBpin (cis). The more
basic zinc reagent and as such the very basic reaction medium also
enable thermodynamically driven cis-to-trans isomerization by a retro-aldol–aldol
process. A broad range of electron-withdrawing groups including electron-deficient
heterocycles is compatible with the different procedures developed.
“…In 2018, Lautens and co-workers reported rhodium-catalyzed alkynylation/aldol cyclization sequence of ketoenones, which can synthesize cyclic α-propargyl-β-hydroxyketones with high enantio- and diastereoselectivity (Scheme 28). 46 Using ( S )-BINAP as the chiral ligand, a wide range of six-membered products were synthesized with excellent enantio- and diastereoselectivities of 89–99% ee and dr >20 : 1. In the proposed reaction mechanism, alkynylrhodation of enone by rhodium-alkynyl species B generates (oxa-π-allyl)rhodium intermediate C .…”
Section: Alkynyl Carbon–carbon Bond Cleavage Of Propargylic Alcoholsmentioning
It is of great significance to realize the alkynylation of the reaction since alkynes are widely present in natural products and biologically active molecules. And at the same time alkynes...
“…Lautens recently disclosed an alkynylation/aldol cyclization sequence of keto-enones 61, affording cyclic α-propargyl-βhydroxyketones 63 with high enantio-and diastereoselectivity (Scheme 11). 59 A broad range of six-membered adducts was furnished, bearing aliphatic and aromatic groups on both sides of the keto-enone. Several bulky alkynes, including aliphatic ones, were tolerated, but terminal alkynes lead to homodimerization instead.…”
Section: β-Alkynyl Elimination With Rhodiummentioning
The functionalization
of molecules by cleaving inert carbon–carbon
single bonds is regarded as a great synthetic challenge due to their
inherent stability. In recent years, significant progress has been
made in the activation of small rings relying on the release of strain
energy. By contrast, the number of catalytic methodologies for the
activation of unstrained carbon–carbon single bonds is still
limited. This review focuses on the recent developments in transition-metal-catalyzed
cleavage of C–C bonds in unstrained alcohols via β-carbon
elimination. Emphasis is placed on the mechanistic aspects of the
discussed transformations and their applications to the deconstruction
and reorganization of molecules.
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