Hydrosiloxane-Ti(OiPr)4: an efficient system for the reduction of primary amides into primary amines as their hydrochloride salts

A simple and useful method for the reduction of primary amides into the corresponding amines using a polymethylhydrosiloxane (PMHS)-Ti(OiPr)₄ reducing system is described. Aromatic as well as aliphatic primary amides are reduced in high selectivity and excellent yields. The reduction could proceed via dehydration of the primary amide group into the corresponding nitrile which is then reduced into the corresponding primary amine.     

Die verwendung von diisobutylaluminiumhydrid zur stereoselektiven synthese von tertiären (e)-2-alkenylaminen, (e)-2-alken-4-inylaminen und 2(

In exploring versatile synthetic routes to (E)-allylamine derivatives with antimycotic properties, a new method has been found in the trans-reduction of tertiary 2-alkinylanunes by diisobutylaluminum hydride (DIBAH). The stereoselectivity of this reaction, which is in contrast to the well-known cis-hydroalumination of disubstituted alkynes, and the regioselectivity have been studied in detail. Tertiary 2-alkinylamines 1 were generally reduced to (E)-2-alkenylamines 2 in toluene at 40°, and tertiary 2,4-alkadiynylamines 3 yielded a mixture of(E)-2-alken-4-ynylamines 4 and 2(E),4(Z)-alkadienylamines 5 in high stereochemical purity. This reduction was clearly different with respect to reactivity and selectivity in comparison with other reactions also proceeding via trans-hydroalumination, namely the lithium aluminum hydride reduction of α-hydroxyacetylenes and the reaction of alkynes with LiAlH(iso-Bu)₂(n-Bu). Tertiary 6-hydroxy-2, 4-alkadiynylamines 10 were reduced to 6-hydroxy-2(E)-alken-4-ynylamines 11 with diisobutylaluminum hydride, whereas on treatment with lithium aluminum hydride 6-hydroxy-4(E)-alken-2-ynylamines 12 were obtained. LiAlH (iso-Bu)₂(n-Bu) did not react with 2-alkinylamine 1a and the 2,4-alkadiynylamine 3a was only monohydroaluminated without discrimination of the two acetylene groups. A possible mechanism for the diisobutylaluminum hydride reduction of 2-alkinylamines is presented.     

Thermal decomposition of products of the addition of diisobutylaluminum hydride to nitriles

Summary In the thermal decomposition of the products of the addition of diisobutylaluminum hydride to nitriles RCH =NA1 (1-C₄H₉)₂, isobutene is liberated and the corresponding amines RCH₂H₂ are formed after hydrolysis of the residue.     

Mechanistic Insights on Reduction of Carboxamides by Diisobutylaluminum Hydride and Sodium Hydride−Iodide Composite

The reaction mechanisms on reduction of tertiary carboxamides by diisobutylaluminum hydride (DIBAL) and sodium hydride (NaH)‐sodium iodide (NaI) composite were elucidated by the computational and experimental approaches. Reduction of N,N‐dimethyl carboxamides with DIBAL provides the corresponding amines, whereas that with the NaH?NaI composite exclusively forms aldehyde even at high reaction temperature. DFT calculations revealed that dimeric structural nature of DIBAL and Lewis acidity on its Al center play crucial role to decompose the tetrahedral anionic carbinol amine intermediate through C?O bond cleavage. On the other hand, in the reduction with the NaH?NaI composite, the resulting tetrahedral anionic carbinol amine intermediate could be kept stable, thus providing aldehydes as a sole product by the aqueous workup     

Complexation between α-alkenylaluminum compounds and diisobutylaluminum hydride: The nature of organoaluminum intermediates responsible for the inhibited hydralumination of alkynes

In order to understand the nature of organoaluminum intermediates encountered in the hydralumination of alkynes, NMR spectral and kinetic studies have been carried out on the alkenyl(dialkyl)aluminum systems (I) resulting from the addition of diisobutylaluminum hydride to 4-octyne and to di-t-butylacetylene. A kinetic study of the reaction of a 1/1 mixture of I and diisobutylaluminum hydride with 5-decyne at 50° followed the rate expression v = k(5-decyne)^1.0 (AlH)^0.5. The E^X (apparent) was 23.0 kcal/mole.The aluminum adducts of 4-octyne with one or two equivalents of diisobutylaluminum hydride did not show any temperature-dependence in their NMR spectra. However, those derived from di-t-butylacetylene did reveal the existence of several components, both for the alkenyl(dialkyl)aluminum itself, as well as for the 1/1 admixture of the alkenyl(dialkyl)aluminum with diisobutylaluminum hydride. However, in the temperature range of hydralumination, namely 50°, the diisobutyl(E-4-octenyl)aluminum was shown to be in equilibrium, with triisobutylaluminum.A proposed rationale for the NMR spectral data, formulated with the aid of data from model systems such as bis(E-4-octenyl)aluminum hydride, also offers an insight into the nature and kinetic behavior of organoaluminum intermediates in the hydralumination reaction.     

Highly efficient and diastereoselective gold(I)-catalyzed synthesis of tertiary amines from secondary amines and alkynes: substrate scope and mechanistic insights

An efficient method for the synthesis of tertiary amines through a gold(I)‐catalyzed tandem reaction of alkynes with secondary amines has been developed. In the presence of ethyl Hantzsch ester and [{(tBu)₂(o‐biphenyl)P}AuCl]/AgBF₄ (2 mol %), a variety of secondary amines bearing electron‐deficient and electron‐rich substituents and a wide range of alkynes, including terminal and internal aryl alkynes, aliphatic alkynes, and electron‐deficient alkynes, underwent a tandem reaction to afford the corresponding tertiary amines in up to 99 % yield. For indolines bearing a preexisting chiral center, their reactions with alkynes in the presence of ethyl Hantzsch ester catalyzed by [{(tBu)₂(o‐biphenyl)P}AuCl]/AgBF₄ (2 mol %) afforded tertiary amines in excellent yields and with good to excellent diastereoselectivity. All of these organic transformations can be conducted as a one‐pot reaction from simple and readily available starting materials without the need of isolation of air/moisture‐sensitive enamine intermediates, and under mild reaction conditions (mostly room temperature and mild reducing agents). Mechanistic studies by NMR spectroscopy, ESI‐MS, isotope labeling studies, and DFT calculations on this gold(I)‐catalyzed tandem reaction reveal that the first step involving a monomeric cationic gold(I)–alkyne intermediate is more likely than a gold(I)–amine intermediate, a three‐coordinate gold(I) intermediate, or a dinuclear gold(I)–alkyne intermediate. These studies also support the proposed reaction pathway, which involves a gold(I)‐coordinated enamine complex as a key intermediate for the subsequent transfer hydrogenation with a hydride source, and reveal the intrinsic stereospecific nature of these transformations observed in the experiments.     

nBu4NI-catalyzed oxidative amidation of aldehydes with tertiary amines

An efficient oxidative coupling protocol for amide formation has been developed. Various tertiary amines and aromatic aldehydes were oxidized to their corresponding tertiary amides in moderate to good yields in the presence of a simple nBu₄NI-catalyst.     

Preparation of high cis‐1,4 polyisoprene with narrow molecular weight distribution via coordinative chain transfer polymerization

High cis‐1,4 polyisoprene with narrow molecular weight distribution has been prepared via coordinative chain transfer polymerization (CCTP) using a homogeneous rare earth catalyst composed of neodymium versatate (Nd(vers)₃), dimethyldichlorosilane (Me₂SiCl₂), and diisobutylaluminum hydride (Al(i‐Bu)₂H) which has strong chain transfer affinity is used as both cocatalyst and chain transfer agent (CTA). Differentiating from the typical chain shuttling polymerization where dual‐catalysts/CSA system has been used, one catalyst/CTA system is used in this work, and the growing chain swapping between the identical active sites leads to the formation of high cis‐1,4 polyisoprene with narrowly distributed molecular weight. Sequential polymerization proves that irreversible chain termination reactions are negligible. Much smaller molecular weight of polymer obtained than that of stoichiometrically calculated illuminates that, differentiating from the typical living polymerization, several polymer chains can be produced by one neodymium atom. The effectiveness of Al(i‐Bu)₂H as a CTA is further testified by much broad molecular weight distribution of polymer when triisobutylaluminum (Al(i‐Bu)₃), a much weaker chain transfer agent, is used as cocatalyst instead of Al(i‐Bu)₂H. Finally, CCTP polymerization mechanism is validated by continuously decreased M_w/M_n value of polymer when increasing concentration of Al(i‐Bu)₂H extra added in the Nd(ver)₃/Me₂SiCl₂/Al(i‐Bu)₃ catalyst system. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2010     

Isoquinoline derivatives VI. Synthesis and pharmacological properties of 4,6,7-substituted 1(2)-arylalkyl-1,2,3,4-tetrahydroisoquinolines and their analogs

The condensation of 6,7-dimethoxy-1,2.3.4-tetrahydroisoquinoline (II) with diphenylacetyl and diphenylpropionyl chlorides gave the corresponding amides (III). Reduction of III with lithium aluminum hydride converted them to tertiary amines IV, which were characterized as their hydrochlorides. The condensation of equimolecular amounts of amines I with the acid chlorides of substituted phenylacetic and diphenylpropionic acids gave amides V. The reduction of amides V with lithium aluminum hydride gave secondary amines VI. The corresponding tetrahydroisoquinolines (VII) were obtained by the cyclization of amides V and subsequent reduction with lithium aluminum hydride, The condensation of 1-diphenylethyl-6,7-dimethoxy-l,2,3,4-tetrahydroisoquinoline with formalin gave VIII. The IR spectra of the synthesized compounds were examined. The effect of these compounds on the arterial blood pressure and the coronary blood flow was studied.See [1] for communication V.Deceased.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 12, pp. 1683–1687, December, 1971.     

Bis-aluminated triflic amide promoted Diels-Alder reactions of α,β-unsaturated lactones

The bis-aluminated triflic amides such as TfN[Al(Me)Cl]₂ and TfN[Al(iBu)₂]₂, which are derived from triflic amide (1 mol) and aluminum reagent (2 mol), can efficiently promote the Diels-Alder reaction of α,β-unsaturated lactone derivatives as dienophiles. Selection of the ligand on aluminum of these Lewis acids should be important depending on the combination of dienophile and 1,3-diene.     

Hydrocarbon Soluble Alkali-Metal-Aluminium Hydride Surrog[ATES]

A series of group 1 hydrocarbon-soluble donor free aluminates [AM(^tBuDHP)(TMP)Al(ⁱBu)₂] (AM=Li, Na, K, Rb) have been synthesised by combining an alkali metal dihydropyridyl unit [(2-^tBuC₅H₅N)AM)] containing a surrogate hydride (sp³ C−H) with [(ⁱBu)₂Al(TMP)]. These aluminates have been characterised by X-ray crystallography and NMR spectroscopy. While the lithium aluminate forms a monomer, the heavier alkali metal aluminates exist as polymeric chains propagated by non-covalent interactions between the alkali metal cations and the alkyldihydropyridyl units. Solvates [(THF)Li(^tBuDHP)(TMP)Al(ⁱBu)₂] and [(TMEDA)Na(^tBuDHP)(TMP)Al(ⁱBu)₂] have also been crystallographically characterised. Theoretical calculations show how the dispersion forces tend to increase on moving from Li to Rb, as opposed to the electrostatic forces of stabilization, which are orders of magnitude more significant. Having unique structural features, these bimetallic compounds can be considered as starting points for exploring unique reactivity trends as alkali-metal-aluminium hydride surrog[ATES].     

Convenient synthesis of trans-3-amino-1-benzylpiperidin-4-ols using regiospecific cleavage of 1-benzyl-3,4-epoxypiperidine with diisobutylaluminum amides (DIBAL-NR1R2)

The report presents a first example of a regio- and stereospecific Lewis acid-catalyzed aminolysis of 1-benzyl-3,4-epoxypiperidine leading to trans-3-amino-1-benzylpiperidin-4-ols, in contrast with other Lewis acid-catalyzed reactions leading to trans-4-amino-1-benzylpiperidin-3-ols. The reaction is performed at room temperature using the reagents prepared by interaction of a hard Lewis acid – diisobutylaluminum hydride (DIBAL-H) with primary and secondary amines. The obtained products are potential intermediates on the way to stereochemical analogues of the antitumor piperidine alkaloid pseudodistomin D.     

Supported Gold Nanoparticles for Efficient α‐Oxygenation of Secondary and Tertiary Amines into Amides

Although the α‐oxygenation of amines is a highly attractive method for the synthesis of amides, efficient catalysts suited to a wide range of secondary and tertiary alkyl amines using O₂ as the terminal oxidant have no precedent. This report describes a novel, green α‐oxygenation of a wide range of linear and cyclic secondary and tertiary amines mediated by gold nanoparticles supported on alumina (Au/Al₂O₃). The observed catalysis was truly heterogeneous, and the catalyst could be reused. The present α‐oxygenation utilizes O₂ as the terminal oxidant and water as the oxygen atom source of amides. The method generates water as the only theoretical by‐product, which highlights the environmentally benign nature of the present reaction. Additionally, the present α‐oxygenation provides a convenient method for the synthesis of ¹⁸O‐labeled amides using H₂¹⁸O as the oxygen source.     

Preparation and some reactions of 3,5:8,10-di-1,3-benzo[8](3,4)-1,2,5-thiadiazolocyclophane

Titled 1,2,5-thiadiazolometacyclophane 1 was prepared via thia[2.3]cyclophane 5 which was obtained by the reaction of di(bromomethyl) 2 with sodium sulfide under phase-transfer-catalyzed conditions. Cyclophane 1 gave the corresponding pyrene derivatives by the oxidative transannular reaction in the reaction with brominating reagent. Reduction of 1 with lithium aluminum hydride followed by acetylation with acetic anhydride gave a 4:l-mixture of cis- and trans-diamide 11 and 12 with a trace amount of cyclophane-ring-cleaved product 13 . On the other hand, 13 was obtained as a major product in the reduction with metal sodium and diisobutylaluminum hydride.     

Novel and efficient method for esterification, amidation between carboxylic acids and equimolar amounts of alcohols, and amines utilizing Me2NSO2Cl and N,N-dimethylamines; its application to the synthesis of coumaperine, a natural chemopreventive dieneamide

Various carboxylic esters or amides were prepared in good to excellent yield between carboxylic acids and equimolar amounts of alcohols or amines under very mild conditions (0-45°C; within 3 h) using dimethylsulfamoyl chloride (Me₂NSO₂Cl; 1) combined with N,N-dimethylamines (Me₂NR: 2a; R=Me, 2b; R=Bu). The choice of the sulfamoyl chloride and the amine is crucial for the reaction; that is, sterically uncrowded amines accelerated the present esterification and amidation. This agent had some advantages over methanesulfonyl chloride (3)/amines as for the atom-economy, avoidance of side reactions, and had very high chemoselectivity toward the carboxyl group vs the hydroxyl group; the experiment was performed by the addition of 1 to the mixture of carboxylic acids and alcohols. Application of this method to the synthesis of coumaperine, a chemopreventive natural product, was performed using the present amidation as a key step.     

Development of general methods for the synthesis of new substituted allyl bromides as promising alkenylating agents

A general procedure has been developed for the synthesis of hitherto unknown substituted allyl bromides. The procedure includes preparation of the corresponding α,β-unsaturated carboxylic acid esters from accessible ketones according to the Horner-Emmons reaction, reduction of these esters with diisobutylaluminum hydride to allylic alcohols, and substitution of the hydroxy group by bromine by the action of PBr₃. The E,Z isomer ratio of the synthesized unsaturated compounds ranges from 3: 1 to 4: 1.     

One-step conversion to tertiary amines: InBr3/Et3SiH-mediated reductive deoxygenation of tertiary amides

We have developed a simple and practical procedure for a direct reductive conversion from a variety of tertiary amides to the corresponding tertiary amines using an InBr₃/Et₃SiH reducing system. This reducing system can be applied to the reduction of a secondary amide and provides a more efficient alternative to conventional methods that use aluminum and boron hydrides.     

EINIGE NEUE THIOPHOSPHINSÄUREAMIDE R2P(S)NHR': SYNTHESE UND KERNRESONANZSPEKTROSKOPISCHE UNTERSUCHUNGEN

Abstract

P.P-Dialkylthiophosphinsäureamide R₂P(S)NHR' (R=Me, 'Pr, 'Bu; R'=Me, Et, ⁱPr. ^cHex. ^tBu. Ph. etc.) wurden erhalten durch Umsetzung von R₂PNHR' mit Schwefel oder durch Reaktion von Me₂P(S)CI mit primaren Aminen. Ihre ³¹P- und ¹³C-NMR-Spektren werden diskutiert. Insbesondere die Di-t-butylthiophosphinsäureamide sind auszilg;ergewöhnlich stabil gegen Hydrolyse und Luftsauerstoff. P,P-Dialkylthiophosphinic acid amides R₂P(S)NHR' (R=Me. ⁱPr. ^tBu; R'=Me, Et, ⁱPr, ^cHex. ^tBu, Ph. etc.) have been obtained by reaction of the corresponding aminophosphines with sulfur or by reaction of dimethylthiophosphorylhalides with primary amines. Their ³¹P- and ¹³C-NMR spectra are discussed. The di-t-butylthiophosphinic compounds proved to be remarkably stable against moisture and oxygen.     

Improved Preparation of (E)-3-Trimethylsilyl-2-Buten-1-OL

An improved preparation of (E)-3-trimethylsilyl-2-buten-1-ol is described. The two-step process entails stereo-selective addition of (TMS)₂ CuLi-LiCN to ethyl tetrolate followed by reduction with diisobutylaluminum hydride and proceeds in 90% overall yield.     

Stereoselective synthesis of 2-aryl-4-en-1-ols,promising synthons for the preparation of oxygen heterocycles

Reactions of arylacetic acids with N-methoxymethanamine afford corresponding Weinreb amides which at alkenylation with methallyl and prenyl bromides in the presence of (Me₃Si)₂N^–Na⁺ form unsaturated amides ArCHRCONMe(OMe) (R = CH₂CMe=CH₂, CH₂C=CMe₂). Amides readily react with BuLi and BnMgCl to give ketones ArCHRCOR' (R' = Bu, Bn). A stereoselective reduction of the latter with LiBH(s-Bu)₃ leads to a quantitative formation of syn-isomers of 2-aryl-4-en-1-ols.