5 research outputs found
Alkynyl Moiety for Triggering 1,2-Metallate Shifts:Enantiospecific sp<sup>2</sup>–sp<sup>3</sup> Coupling of Boronic Esters with p-Arylacetylenes
Enantiospecific sp(2)-sp(3) coupling of secondary and tertiary boronic esters
The cross-coupling of boronic acids and related derivatives with sp(2) electrophiles (the Suzuki-Miyaura reaction) is one of the most powerful C-C bond formation reactions in synthesis, with applications that span pharmaceuticals, agrochemicals and high-tech materials. Despite the breadth of its utility, the scope of this Nobel prize-winning reaction is rather limited when applied to aliphatic boronic esters. Primary organoboron reagents work well, but secondary and tertiary boronic esters do not (apart from a few specific and isolated examples). Through an alternative strategy, which does not involve using transition metals, we have discovered that enantioenriched secondary and tertiary boronic esters can be coupled to electron-rich aromatics with essentially complete enantiospecificity. As the enantioenriched boronic esters are easily accessible, this reaction should find considerable application, particularly in the pharmaceutical industry where there is growing awareness of the importance of, and greater clinical success in, creating biomolecules with three-dimensional architectures.</p
Concurrent Biocatalytic Oxidation and C–C Bond Formation via Gold Catalysis: One-Pot Alkynylation of N-Alkyl Tetrahydroisoquinolines
Development of Enantiospecific Coupling of Secondary and Tertiary Boronic Esters with Aromatic Compounds
The stereospecific
cross-coupling of secondary boronic esters with
sp<sup>2</sup> electrophiles (Suzuki–Miyaura reaction) is a
long-standing problem in synthesis, but progress has been achieved
in specific cases using palladium catalysis. However, related couplings
with tertiary boronic esters are not currently achievable. To address
this general problem, we have focused on an alternative method exploiting
the reactivity of a boronate complex formed between an aryl lithium
and a boronic ester. We reasoned that subsequent addition of an oxidant
or an electrophile would remove an electron from the aromatic ring
or react in a Friedel–Crafts-type manner, respectively, generating
a cationic species, which would trigger 1,2-migration of the boron
substituent, creating the new C–C bond. Elimination (preceded
by further oxidation in the former case) would result in rearomatization
giving the coupled product stereospecifically. Initial work was examined
with 2-furyllithium. Although the oxidants tested were unsuccessful,
electrophiles, particularly NBS, enabled the coupling reaction to
occur in good yield with a broad range of secondary and tertiary boronic
esters, bearing different steric demands and functional groups (esters,
azides, nitriles, alcohols, and ethers). The reaction also worked
well with other electron-rich heteroaromatics and 6-membered ring
aromatics provided they had donor groups in the meta position. Conditions
were also found under which the BÂ(pin)- moiety could be retained in
the product, ortho to the boron substituent. This protocol, which
created a new CÂ(sp<sup>2</sup>)–CÂ(sp<sup>3</sup>) and an adjacent
C–B bond, was again applicable to a range of secondary and
tertiary boronic esters. In all cases, the coupling reaction occurred
with complete stereospecificity. Computational studies verified the
competing processes involved and were in close agreement with the
experimental observations