One-pot two-step conversion of aromatic carboxylic acids and esters to aromatic aldehydes via indium-catalyzed reductive thioacetalization and desulfurization

Described herein is that a new approach to a one-pot two-step conversion of aromatic carboxylic acids/esters to aromatic aldehydes, in which indium(III) iodide effectively catalyzes both the first reductive thioacetalization of carboxylic acids and a subsequent desulfurization of the in-situ formed thioacetal intermediates leading to aldehydes.     

One step synthesis of indirubins by reductive coupling of isatins with KBH4

One step synthesis of the natural product indirubin by reductive coupling of isatin with KBH₄ is described and a possible mechanism for the reaction is proposed. Eleven indirubin derivatives were obtained easily from the corresponding substituted isatin.     

Synthesis of azo compounds by nanosized iron-promoted reductive coupling of aromatic nitro compounds

Treatment of a variety of aromatic nitro compounds with the active-iron based reducing system composed of FeCl₂·4H₂O, an excess of lithium powder and a catalytic amount of 4,4′-di-tert-butylbiphenyl (DTBB, 5 mol %) in THF at room temperature, led to the formation of the corresponding symmetrically substituted azo compounds in good yield, resulting from a reductive coupling process. Some other functionalities including carbonyl, halogen, amino and hydroxyl groups, demonstrated to be compatible with the reaction conditions, giving none reduced or coupled by-products. In all cases, the azo compounds formed have not experienced over-reduction to the corresponding hydrazo or amino derivatives even upon prolonged heating or using an excess of the reducing system.     

Asymmetric synthesis of α-chiral dihydrocinnamates by catalytic reductive aldol coupling and subsequent dehydroxylation

Optically active dihydrocinnamate derivatives bearing the chiral carbon center at α-position were synthesized by Rh(Phebox)-catalyzed asymmetric reductive aldol coupling reaction with substituted cinnamates and benzaldehyde derivatives and subsequent dehydroxylation reaction.     

The breaking and mending of porphyrins: reductive coupling of secochlorin bisaldehydes

The reaction of free base or Ni(II) complex secochlorin bisaldehydes 4H₂ and 4Ni regenerates the ultimate starting material of the bisaldehydes, meso-tetraphenylporphyrin 2H₂ and 2Ni, respectively. Depending on the reaction conditions employed (hydrazine hydrate in pyridine at reflux or hydrazine hydrate activated with sulfur in the presence of aqueous NaOH at ambient temperature), either porphyrin 2H₂ is formed together with known dihydroxymorpholinochlorin 9H₂ or known 2-hydroxychlorin 8H₂. Two different reaction pathways for the hydrazine reaction can be derived, either involving the formation of a meso-tetraphenyl-1,4,5-triazepinoporphyrin that loses spontaneously N₂ or a Wolff-Kishner-type pathway that also involves an intramolecular aldol-type reaction. Neither reaction is synthetically useful but both highlight in an impressive fashion the high thermodynamic stability of porphyrins. They also bring the ‘breaking and mending of porphyrin’ strategy to its ultimate conclusion by regenerating the starting porphyrin.     

E-Stilbene derivatives synthesized by stereoselective reductive coupling of benzylic gem-dibromide promoted by Cu/polyamine

Stereoselective reductive coupling reaction of benzylic gem-dibromide promoted by Cu/polyamine produces E-stilbene derivatives with high yield under mild conditions. It provides a short pathway to synthesize symmetrical and asymmetrical E-stilbene derivatives using cheap reagents and alkenyl-free starting material together with easy workup.     

Nickel-mediated reductive coupling of neopentyl bromides with activated alkenes at room temperature and its synthetic application

Reductive coupling of sterically hindered neopentyl bromides with activated alkenes mediated by the in situ generated Ni(0) complexes along with some feedstock is achieved in good yield under the mild conditions. This practically useful method of C(sp³)−C(sp³) bond formation provides a complementary approach to the traditional conjugate addition of preformed organometallic reagents to electrophilic olefins, which often requires cryogenic temperature and rigorous exclusion of air and moisture. The robust application of this reductive coupling reaction was demonstrated in a formal synthesis of stereodivergent (−)-copacamphor and (−)-ylangocamphor, which are valuable intermediates for a class of tricyclo[5.3.0.0^3,8]decane sesquiterpenes. Moreover, this convenient protocol resulted in a facile access to the homolog of Corey aldehyde en route to prostaglandins, implying the possible involvement of radical-like species.     

One-pot reductive amination of aldehydes catalyzed by a hydrio-iridium(III) complex in aqueous medium

A combination of sodium tetrakis[3,5-di(trifluoromethyl)phenyl]borate [NaBAr^F₄] and hydrio-iridium(III) complex efficiently catalyzed the one-pot reductive amination of aldehydes with various amines and ammonia in water under mild conditions in good to excellent yields.     

Reductive coupling reaction of aldehydes using indium(III) triflate as the catalyst

A reductive coupling reaction was effectively developed to convert an aldehyde to its symmetrical ether. The successful reactions required Et₃SiH and CH₂Cl₂ as the suitable solvent in the presence of a catalytic amount of In(OTf)₃. Various aldehydes were subjected to the method, and each afforded the expected ethers in good to excellent yields.     

Intermolecular reductive coupling of hindered N-aryl imines towards the modular synthesis of chiral N-heterocyclic carbenes

We describe a simple method for the synthesis of hindered N-aryl diamines. The diastereoselectivity for these processes are relatively low but the diamines can be separated using either chromatography or selective crystallization. Separation of enantiomers can be accomplished using HPLC equipped with a chiral stationary phase.     

One-pot derivatization of medicinally important 9-aminoacridines by reductive amination and SNAr reaction

A new highly efficient one-pot derivatization of medicinally important 9-aminoacridines (9-AA) at the amine position is described. Simple reductive amination and S_NAr reaction using easily accessible starting materials give a fast entry to novel 9-AA derivatives for biological screening.     

Synthesis of 1,2,9,10-tetrakis(N-phenylamino)[2.2]metacyclophane by SmI2-mediated reductive coupling of diimine

SmI₂/HMPA-mediated double reductive coupling of N,N′-(m-xylylidene)dianiline affords 1,2,9,10-tetrakis(N-phenylamino)[2.2]metacyclophane in good yield.     

An unexpected product from attempted reductive etherification of a silyl alcohol with an aldehyde

Reductive etherification, using BiBr₃/Et₃SiH, between two modified amino acids, one with a silyl alcohol side chain and one with an aldehyde side chain, gave, not the desired bis-amino acid, but a tetrahydrooxazine, in good yield.     

One-pot preparation of hydroxylated potassium organotrifluoroborates and subsequent Jones oxidation to potassium organocarbonyltrifluoroborates

Alcohol-containing potassium organotrifluoroborates as starting reagents were prepared from their corresponding dibromobenzenes through a sequential one-pot reaction. The oxidation reactions of these substrates, which were carried out using 3.0 equiv of 8 N Jones reagent in acetone at 0 °C, provided a high yield of the desired carbonyl-functionalized compounds. In addition, the cross-coupling reactions of these organocarbonyltrifluoroborates were successfully performed in the presence of 3 mol % of Pd(PPh₃)₄ catalyst at 100 °C.     

A novel one-step method for the reductive allylation of esters and the first total synthesis of (±)-erythrococcamide B

A novel and convenient one-step method for the reductive allylation of aliphatic and alicyclic esters using InBr₃ as a catalyst is reported. This methodology has also been applied in the first total synthesis of (±)-erythrococcamide B.     

Generation of quaternary centers by reductive cross-coupling: shifting of regioselectivity in a subset of allylic alcohol-based coupling reactions

Regioselective titanium alkoxide-mediated reductive cross-coupling reactions of allylic alcohols with vinylsilanes and imines have previously been demonstrated to proceed with allylic transposition by formal metallo-[3,3]-rearrangement [thought to proceed by a sequence of: (1) directed carbometalation, and (2) syn-elimination]. While many examples have been described that support this reaction path, a collection of substrates have recently been identified that react by way of an alternative pathway, delivering a concise convergent route to coupled products bearing a quaternary center.     

Reduction and reductive coupling of imines by Sm(II)-based reagents

The reductive coupling of aldimines and ketimines by a series of Sm(II)-based reagents (SmI₂, SmI₂–HMPA, SmBr₂, Sm{N[Si(CH₃)₃]₂}₂, and SmI₂/triethylamine/water) were examined. In general, aldimines and ketimines were efficiently reduced or coupled using reductants that are more powerful than SmI₂, and the use of Sm{N[Si(CH₃)₃]₂}₂ led to higher diastereoselectivities in reductive coupling reactions. Surprisingly, only the combination of SmI₂/triethylamine/water was capable of reducing and coupling para-substituted benzaldimines and coupling ketimines.     

Direct Leuckart-type reductive amination of aldehydes and ketones: a facile one-pot protocol for the preparation of secondary and tertiary amines

A high-yielding and facile one-pot Leuckart-type reaction for rapid access to a number of 2° and 3° amines is described.     

Stereoselective synthesis of (+)-cryptocarya diacetate by an iterative Prins cyclisation and reductive cleavage sequence

A highly stereoselective synthesis of (+)-cryptocarya diacetate is achieved through our recently developed strategy for the construction of 1,3-diols via Prins cyclisation. The route relies mainly on the reductive cleavage of allylic ethers, ozonolysis and Wittig olefination along with Prins cyclisation.     

ZrCl4/Hantzsch 1,4-dihydropyridine as a new and efficient reagent combination for the direct reductive amination of aldehydes and ketones with weakly basic amines

ZrCl4/Hantzsch 1,4-dihydropyridine is a mild and highly efficient reagent combination for the direct reductive amination.Weakly basic amines such as anilines substituted by electron-withdrawing group and heteroaromatic amines can be reductivelyalkylated with electron rich aldehydes and ketones under mild conditions to form the secondary amines in excellent yields.