A Safer Reduction of Carboxylic Acids with Titanium Catalysis

Abstract

Ammonia-borane, shown previously to react with carboxylic acids under reflux to form primary amides, reduces acids to alcohols at room temperature in the presence of catalytic TiCl 4 . The process, which is tolerant of a variety of potentially reactive functional groups, including N-protected amino acids, can be employed for the selective reduction of acids in the presence of amides, nitriles and, to some extent, esters. Aliphatic acids can be selectively reduced in the presence of aromatic acids.

Balancing Lewis Acidity and Carbocation Stability for the Selective Deoxyhalogenation of Aryl Carbonyls and Carbinols

“…Hypothesizing that the deoxyhalogenation is proceeding via the alcohol, an investigation of carboxylic acids was undertaken because they also have been reduced to the alcohol using TiCl 4 and BH 3 NH 3 . A series of benzoic acids ( 1ad – 1ai ) and arylacetic acids ( 1aj – 1al ) were successfully converted to the corresponding chloromethanes by using a tandem one-pot reduction halogenation.…”

“…Substrates with small −σ value substituents did not deviate from the optimized conditions (1r, 1s), but decreasing −σ values frequently resulted in the exhaustive reduction of the ketone to the corresponding methylene moiety. 20 Curiously, homobenzylic ketone 1t was converted to the corresponding alcohol exclusively when using diethyl ether (Et 2 O) but provided 52% of the chloride when the solvent was switched to refluxing dichloroethane (DCE).…”

Additive-free reductive hydrodeoxygenation of fatty acids catalyzed by inexpensive simple nickel(ii) compounds

“…Among these, first-row transition metal catalysts are particularly interesting because of their high natural abundance and low cost. Homogeneous catalytic systems for the HDO of FAs have been reported using Ti, 7 Fe, 8 Co, 9 and Ni. 10 However, these systems need either high hydrogen pressures or toxic and dangerous additives and reagents that could become a problem for large scale synthesis.…”

Catalyst- and Stoichiometry-Dependent Deoxygenative Reduction of Esters to Ethers or Alcohols with Borane–Ammonia

“…Reactions in other common solvents, such as acetonitrile (CH 3 CN), dichloroethane (DCE), and tetrahydrofuran (THF) (entries 4−6), confirmed that Et 2 O is the solvent of choice. Notably, THF and DCE were completely ineffective (entries 5−6), while DCM and CHCl 3 provided the corresponding deoxyhalogenation36 product, benzyl chloride (not shown in Table2).A series of other Lewis acid catalysts (TiBr 4 , HfCl 4 , AlCl 3 , FeCl 3 , and BF 3 −Et 2 O) were also examined. Low or no…”

“…The widely varying product outcomes obtained for the various borane–amines are believed to be a result of variations in reducing strength arising from the differences in sterics and basicity of the coordinated amine. Similar variations were also reported for ketone and carboxylic acid reductions. , …”