Contrary to the accepted convention, this work shows that Minisci-type C-H alkylation does not require any metal, photocatalyst, light, or prefunctionalization of the readily available and inexpensive carboxylic acids to proceed well under mild conditions. These mild conditions can be utilized for late-stage alkylations of complex molecules, including pharmaceutical compounds and light-sensitive compounds which degrade under photocatalytic conditions.
A catalytic enantioselective addition reaction of alkylzirconium species to aromatic aldehydes is reported. The reaction, facilitated by a chiral nonracemic diol ligand complex with Ti(OiPr)4, proceeds under mild and convenient conditions, and no premade organometallic reagents are required since the alkylzirconium nucleophiles are generated in situ by hydrozirconation of alkenes with the Schwartz reagent. The methodology is compatible with functionalized nucleophiles and a broad range of aromatic aldehydes.
Aldehydes/chemistry , Organometallic Compounds/chemistry , Alkenes/chemistry , Catalysis , Molecular Structure , Titanium/chemistry
A general synthetic route to γ-oxo alkyl or α-hydroxy benzyl 2-substituted benzoquinones has been developed through a one-pot Rh-catalyzed C-C bond formation/oxidative demethylation sequence from 2,5-dimethoxy aryl boronic acids and several electron deficient alkenes or aldehydes. The process allows rapid access to functionalized benzoquinones under very mild conditions and good yields. We disclose the first example of a Rh-catalyzed 1,4-addition reaction of benzoquinonyl boronic acid to methyl vinyl ketone and other conjugate acceptors, which allows the direct synthesis of 2-(γ-functionalized alkyl) substituted benzoquinones.
Nitrofurans undergo intramolecular Diels-Alder reactions with tethered electron-poor dienophiles more rapidly and in higher yield than non-nitrated furans. Computational studies indicate that increased stabilization of a partial positive charge on the nitro-substituted carbon in both transition state and product is the driving force for these reactions. Frontier molecular orbital energy differences indicate a switch from normal to inverse electron demand upon nitration. There does not appear to be a contribution from any differences in aromatic stabilization energy between furans and nitrofurans. Calculations show that the nitrofuran reactions proceed via a highly asynchronous transition state allowing easier bond formation between two sterically hindered carbons.
Indole substituted twistane-like derivatives resulted in a reaction between 3,5-dimethyl-2-quinonyl boronic acid and 2-alkenyl indoles. Their MCPBA oxidation gave 6/6/9 caged systems. Boronic acid acts as a temporal promoter allowing a site-selective conjugate addition of the heteroaromatic system to the methyl substituted C-3 quinone carbon, giving an intermediate diene which is regioselectively trapped by intramolecular [4 + 2] cycloaddition.
Reactions of heteroaromatic compounds with 3-methyl substituted 2-quinonyl boronic acids proceeded by 1,4-addition followed by spontaneous protodeboronation, leading directly to the Friedel-Crafts alkylation products instead of the commonly observed alkenylation derivatives resulting from quinones. The boronic acid acts as a temporary regiocontroller, making the system a highly reactive quinone equivalent and opening a direct access to 5,5-disubstituted cyclohexene-1,4-diones.
Substituted 2-quinonyl boronic acids have been synthesised from 1,4-dimethoxy aromatic derivatives in two steps: regiocontrolled boronation and oxidative demethylation. The study of their dienophilic behaviour evidenced that the boron substituent significantly increases the reactivity and triggers an efficient domino process in which the Diels-Alder reaction was followed by a protodeboronation or dehydroboronation, depending on the substitution on both the quinone and diene partners. The boronic acid acts as a temporary controller, opening a direct access to trans-fused meta-regiosomeric adducts when 3-methyl-substituted 2-quinonyl boronic acids react with dienes with a substituent at C-1. A particularly valuable synthetic result was obtained in the reaction between 3,6-dimethyl-2-quinonyl boronic acid and piperylene under an oxygen atmosphere; trans-fused 8a-hydroxy-2,4a,8-trimethyl tetrahydronaphthoquinone was formed directly, in excellent yield and in a highly diastereoselective manner.
Benzoquinones/chemistry , Boronic Acids/chemistry , Crystallography, X-Ray , Hydrogen Bonding , Molecular Conformation , Oxidation-Reduction , Stereoisomerism
