An unprecedented C-C coupling reaction between alkenes and ketones by hydrogen-atom transfer, using Fe(acac) and PhSiH in EtOH, is described. This mild protocol features high site selectivity and allows the construction of sterically congested structures containing tertiary alcohols and quaternary centers. The overall process introduces a novel strategic bond disconnection for ring-closing reactions.
A general method for the synthesis of amides involving the direct coupling of alkali metal carboxylate salts with amines is described. Amidation of a wide variety of carboxylate salts with either free amines or their ammonium hydrochloride salts can be achieved using HBTU as a coupling agent in combination with Hünig's base. The reaction is highly efficient and is generally complete in as little as 1-2 h, giving the products in good to excellent yields. The protocol is valuable for the coupling of carboxylates for which the corresponding carboxylic acids or acyl chlorides are unstable, less conveniently manipulated/isolated, or are not commercially available. For example, the coupling of amines and α-amino acids with lithium 5-bromo-1H-pyrrole-2-carboxylate, whose corresponding acid that is prone to decarboxylation, allowed for the synthesis of 5-bromo-1H-pyrrole-2-carboxamides, which are analogues of the pyrrole-2-aminoimidazole marine alkaloids. The protocol can be combined with other reactions in a sequenced fashion, as exemplified by the synthesis of acetylenic amides, in a one-pot procedure, via the coupling of a lithium carboxylate salt formed initially by the addition of carbon dioxide to a lithiated terminal alkyne.
A revised structure for the Lycopodium alkaloid huperzine N is proposed and confirmed by synthesis. The key synthetic steps involve an epimerization of a cis-5-oxodecahydroquinoline to the corresponding trans isomer and a coupling, followed by a diastereoselective hydrogenation using Wilkinson's catalyst to incorporate the pyridylmethyl moiety. This route allowed the alkaloid serralongamine A to be synthesized for the first time, and two additional steps led to the revised structure of huperzine N, both products bearing an unusual decahydroquinoline stereostructure.
The reduction of alkyl‐substituted benzoic acids with lithium in liquid ammonia has been investigated. Without added proton donor the aromatic acid yields a dianion which can either be protonated with ammonium chloride or alkylated to give the corresponding 1,4‐dihydrobenzoic acid and 1‐alkyl 2,5‐cyclohexadiene‐1‐carboxylic acid, respectively.
In the presence of ethanol, 3‐ and 4‐alkylbenzoic acids yield either 1,4‐dihydro or 4,5‐dihydro products depending on the working up procedure Benzoic acid behaves similarly. Water is shown to be a useful proton donor in the reduction of 3‐ and 4‐alkylbenzoic acids to 1,4‐dihydro products. 2‐Alkylbenzoic acids yield 1,4‐dihydro products, irrespective of the experimental procedure.
Experiments with 4‐deuterobenzoic acid show the first proton addition to be irreversible in ammonia as well as in ammonia‐ethanol.
Some thirty new alkyl‐ and dialkyl‐cyclohexadienecarboxylic acids are described.
A unified strategy for the synthesis of the cis-phlegmarine group of alkaloids is presented, leading to the first synthesis of serratezomine E (1) as well as the putative structure of huperzine N (2). A contrasteric hydrogenation method was developed based on the use of Wilkinson's catalyst, which allowed the facial selectivity of standard hydrogenation to be completely overturned. Calculations were performed to determine the mechanism, and structures for huperzines M and N are reassigned.
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