The stereospecific
cross-coupling of secondary boronic esters with
sp2 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 B(pin)- moiety could be retained in
the product, ortho to the boron substituent. This protocol, which
created a new C(sp2)–C(sp3) 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.
A cross-dehydrogenative coupling process has been developed involving the enzymatic oxidation of tetrahydroisoquinolines (THIQ) together with gold-catalyzed C-C bond-formation. The transformation demonstrates the compatibility of gold mediated chemocatalysis and monoamine oxidase biocatalysis which act co-operatively in one vessel. A range of N-alkyl THIQs were functionalized in this manner at C-(1) position in high yields.
The enantiospecific coupling of secondary and tertiary boronic esters to aromatics has been investigated. Using p‐lithiated phenylacetylenes and a range of boronic esters coupling has been achieved by the addition of N‐bromosuccinimide (NBS). The alkyne functionality of the intermediate boronate complex reacts with NBS triggering the 1,2‐migration of the group on boron to carbon giving a dearomatized bromoallene intermediate. At this point elimination and rearomatization occurs with neopentyl boronic esters, giving the coupled products. However, using pinacol boronic esters, the boron moiety migrates to the adjacent carbon resulting in formation of ortho boron‐incorporated coupled products. The synthetic utility of the boron incorporated product has been demonstrated by orthogonal transformation of both the alkyne and boronic ester functionalities.
Esters. -For the first time, a general method for coupling electron-rich aromatic and heteroaromatic compounds with enantioenriched secondary and tertiary boronic esters is described. The reaction involves initial formation of a boronate complex followed by activation of the electron-rich aromatic moiety by an electrophile (NBS or NIS), which triggers a stereospecific 1,2-migration and subsequent elimination/rearomatization. -(BONET, A.; ODACHOWSKI, M.; LEONORI, D.; ESSAFI, S.; AGGARWAL*, V. K.; Nat. Chem. 6 (2014) 7, 584-589, http://dx.
The enantiospecific coupling of secondary and tertiary boronic esters to aromatics has been investigated. Using p-lithiated phenylacetylenes and ar ange of boronic esters coupling has been achieved by the addition of Nbromosuccinimide (NBS). The alkyne functionality of the intermediate boronate complex reacts with NBS triggering the 1,2-migration of the group on boron to carbon giving ad earomatized bromoallene intermediate.A tt his point elimination and rearomatization occurs with neopentyl boronic esters,g iving the coupled products.H owever,u sing pinacol boronic esters,t he boron moiety migrates to the adjacent carbon resulting in formation of ortho boronincorporated coupled products.T he synthetic utility of the boron incorporated product has been demonstrated by orthogonal transformation of both the alkyne and boronic ester functionalities.
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