Diisobutylaluminum Hydride Research Articles

Grignard Reactions in Cyclopentyl Methyl Ether

AbstractWe undertook a systematic study of Grignard reactions using cyclopentyl methyl ether (CPME) as a reaction solvent. Diisobutylaluminum hydride was found to be the most appropriate activator of magnesium and a number of Grignard reagents could be prepared as homogeneous or heterogeneous solutions in CPME. The CPME used in the Grignard reaction was efficiently recycled without affecting the reaction yield of the second experiment. GC–MS analysis of the recovered solvent revealed that CPME was stable under the Grignard conditions. Some of the Grignard reagents in CPME were stable for at least several months and therefore these solutions could replace existing commercial reagents. Tramadol hydrochloride, an analgesic that is used worldwide, and tamoxifen, an anti‐estrogenic drug for estrogen‐receptor‐positive breast cancer were synthesized using Grignard reactions in CPME.

Selective Mono-reduction of Pyrrole-2,5 and 2,4-Dicarboxylates.

Pyrrole-2,5-dicarboxylates were rapidly and selectively reduced to the corresponding mono-alcohol using 3 eq of diisobutylaluminum hydride at 0°C. Pyrrole-2,4-dicarboxylate showed the same reactivity; however, the selectivity decreased with pyrrole-3,4-dicarboxylate. When the nitrogen atom of the pyrrole-2,5-dicarboxylate is protected with a benzyl group, selective mono-reduction does not occur. Considering that furan-2,5-dicarboxylates did not give the corresponding mono-alcohol under the same conditions, the unprotected nitrogen atom of pyrrole apparently plays an important role in this selective mono-reduction.

Synthesis of Plasmonic Cu2-x Se@ZnS Core@Shell Nanoparticles.

We report the synthesis of plasmonic Cu2-x Se@ZnS core@shell nanoparticles (NPs). We used a shell growth approach, starting from Cu2-x Se NPs that have been shown before to exhibit a localized surface plasmon resonance (LSPR). By careful synthesis planning we avoided cation exchange reactions and received core@shell nanoparticles that, after oxidation under air, exhibit a strong LSPR in the NIR. Interestingly, the crystalline, closed ZnS shell that we grew with variable thickness still allowed a slow oxidation of the core under ambient conditions, while the core was effectively protected from reduction, even in the presence of reducing agents such as borane tert-butyamine complex and diisobutylaluminum hydride, giving rise to a stable particle LSPR, also under strongly reducing conditions.

Application of Continuous Flow for DIBAL-H Reduction and n-BuLi Mediated Coupling Reaction in the Synthesis of Eribulin Mesylate

Here we examined the use of continuous flow conditions for the final assembly of eribulin mesylate aimed to avoid cryogenic condition. The diisobutylaluminum hydride reduction of ester 2 to aldehyde 3 and n-butyllithium-mediated coupling of aldehyde 3 and sulfone fragment 4 to produce sulfone-diol 5 were investigated. Under optimized continuous flow conditions, both reactions could be run at temperatures higher than those used under batch conditions. For the diisobutylaluminum hydride reduction of ester 2 to aldehyde 3, under optimized continuous flow conditions at −50 °C, aldehyde 3 was afforded with better HPLC area ratio than it was under batch conditions at −70 °C. Furthermore, continuous operation for 87 min afforded the same quality of 3 as was produced with a short-time operation (yield, 96.5%). For the n-butyllithium-mediated coupling of 3 and 4, under optimized continuous flow conditions at 10 °C, 5 was afforded with a better conversion rate than it was under batch conditions at −70 °C.

ChemInform Abstract: A Two‐Step, One Pot Preparation of Amines via Acyl Succinimides. Synthesis of the Calcimimetic Agents Cinacalcet, NPS R‐467, and NPS R‐568.

Abstract A method has been developed for the preparation of amines through a process of coupling acyl succinimides derived from commercially available carboxylic acids with amines to afford the corresponding amides. These amides are then reduced in situ with either diisobutylaluminum hydride or lithium aluminum hydride. The reaction tandem of the coupling reaction followed by the reduction affords the amine in fair to good yields after purification by flash chromatography. This one-pot, two reaction tandem process has been successfully applied to the synthesis of the calcimimetic agents cinacalcet, NPS R-467, and NPS R-568.

Reduction of λ5‐Phosphinines

AbstractA convenient method to easily prepare parent λ3‐phosphinine from easily accessible λ5‐precursors was developed. A series of λ5‐phosphinines bearing heteroatom substituents OMe, SMe, and/or NMe2 at the phosphorus atom were prepared by electrocyclization of phosphahexatrienes generated in situ. Reaction conditions for the synthesis of λ5‐phosphinines were optimized. The molecular structure of 1,1‐dimethoxy‐λ5‐phosphinine was determined by an X‐ray diffraction analysis. A series of reducing agents were tested in order to prepare λ3‐phosphinine. 1,1‐Dimethoxy‐λ5‐phosphinine was reduced by LiAlH4. The method of choice appeared to be the reduction of bis(dimethylamino)‐λ5‐phosphinine with diisobutylaluminium hydride (DIBAL‐H) in 30 % overall yield starting from vinyl ethyl ether.

One-Step Synthesis of Nitriles from Acids, Esters and Amides Using DIBAL-H and Ammonium Chloride

A convenient, one-step procedure is presented for the conversion of carboxylic acids or their derivatives (esters, lactones, amides) to nitriles with an aminoalane reagent prepared from diisobutylaluminum hydride (DIBAL-H) and ammonium chloride.

Reduction at low temperature of isomentholactone with diisobutylaluminum hydride in CH2Cl2

Reduction at low temperature of isomentholactone with diisobutylaluminum hydride in CH2Cl2

Development of variously functionalized nitrile oxides.

N-Methylated amides (N,4-dimethylbenzamide and N-methylcyclohexanecarboxamide) were systematically subjected to chemical transformations, namely, N-tosylation followed by nucleophilic substitution. The amide function was converted to the corresponding carboxylic acid, esters, amides, aldehyde, and ketone upon treatment with hydroxide, alkoxide, amine, diisobutylaluminium hydride and Grignard reagent, respectively. In these transformations, N-methyl-N-tosylcarboxamides behave like a Weinreb amide. Similarly, N-methyl-5-phenylisoxazole-3-carboxamide was converted into 3-functionalized isoxazole derivatives. Since the amide was prepared by the cycloaddition reaction of ethynylbenzene and N-methylcarbamoylnitrile oxide, the nitrile oxide served as the equivalent of the nitrile oxides bearing a variety of functional groups such as carboxy, alkoxycarbonyl, carbamoyl, acyl and formyl moieties.

Low-temperature reduction of acyclic (–)-mentholactone derivatives with diisobutylaluminum hydride in methylene chloride

Low-temperature treatment of acyclic (–)-mentholactone derivatives with excess diisobutylaluminum hydride in methylene chloride afforded O-isobutyl derivatives of seven-membered lactols. Methyl 6-hydroxy-3,7-dimethyloctanoate behaved similarly to (–)-mentholactone, and its 6-oxo analog, similarly to (–)-mentholactone and isomentholactone.

Low-Temperature Reduction by Diisobutylaluminum Hydride in CH2Cl2 of Seven-Membered Lactones from Betulin and S-(+)-Camphor

The behavior of seven-membered lactones from the triterpenoid betulin and S-(+)-camphor in a novel reaction with organoaluminum compounds was studied using low-temperature reduction of monoterpene sevenmembered lactones by an excess of diisobutylaluminum hydride in CH 2 Cl 2 .

Direct Incorporation of Hydroxy Groups into Isotactic Polypropylene via Metallocene-Catalyzed Copolymerization of Ester Group Containing Vinyl Monomer Treated with Dialkylaluminum Hydride and Propylene

Abstract Methyl 10-undecenoate treated with 2 equivalents of diisobutylaluminum hydride was quantitatively converted into a 10-undecenoxy aluminum compound, which was successfully utilized for metallocene-catalyzed copolymerization with propylene to produce functional polypropylene with hydroxy groups in its side chains.

A two-step, one pot preparation of amines via acyl succinimides. Synthesis of the calcimimetic agents cinacalcet, NPS R-467, and NPS R-568

A method has been developed for the preparation of amines through a process of coupling acyl succinimides derived from commercially available carboxylic acids with amines to afford the corresponding amides. These amides are then reduced in situ with either diisobutylaluminum hydride or lithium aluminum hydride. The reaction tandem of the coupling reaction followed by the reduction affords the amine in fair to good yields after purification by flash chromatography. This one-pot, two reaction tandem process has been successfully applied to the synthesis of the calcimimetic agents cinacalcet, NPS R-467, and NPS R-568.

Lewis base adducts of diisobutylaluminum azide: synthesis and thermal stability

Diisobutylaluminum azide was prepared from the reaction of diisobutylaluminum hydride with trimethylsilyl azide, and it was reacted with five different Lewis bases. The monodentate ligands p-dimethylaminopyridine (DMAP) and the two N-heterocyclic carbenes IMes and IDipp afforded the expected adducts L·Al(i-Bu)2N3 in good yields. Reaction with the bidentate diimine (MesN=CH)2 did not stop at the adduct stage, but continued to form the iminoamide compound {MesNCH2C(i-Bu)NMes}Al(i-Bu)N3 through formal Al-i-Bu addition to one of the N–C double bonds followed by i-Bu migration. The terdentate pincer ligand 2,6-bis(diethylaminomethyl)pyridine induces azide transfer and formation of the ionic compound [2,6-(Et2NCH2)2C5H3NAl(i-Bu)2][(i-Bu)2Al(N3)2]. The compounds are thermally stable to at least 110 °C but decompose either into their precursors or into a mixture of unidentified products. All new compounds were characterized by 1H and 13C{1H} spectroscopy, IR spectroscopy, and the iminoamide compound {MesNCH2C(i-Bu)NMes}Al(i-Bu)N3 was also analyzed by single-crystal X-ray diffraction.

Study for diastereoselective aldol reaction in flow: synthesis of (E)-(S)-3-hydroxy-7-tritylthio-4-heptenoic acid, a key component of cyclodepsipeptide HDAC inhibitors

Flow synthesis of (E)-(S)-3-hydroxy-7-tritylthio-4-heptenoic acid (5), a key component of cyclodepsipeptide histone deacetylase inhibitors was achieved. An efficient flow system for the synthesis of α, β-unsaturated ester 8 was established using a flow reactor column packed with polymer-supported 1,4-diazabicyclo[2.2.2]octane and a fast mixing accessible flow reactor (Comet X-01). Enal 9 was efficiently prepared by a partial reduction of the α, β-unsaturated ester 8 using diisobutylaluminium hydride in the flow system, and the continuous-flow diastereoselective aldol reaction was performed at low temperature, giving a good yield and diastereoselectivity of the desired aldol 10.

ChemInform Abstract: Alkylation of Pyridines at Their 4‐Positions with Styrenes Plus Yttrium Reagent or Benzyl Grignard Reagents.

A new regioselective alkylation of pyridines at their 4-position was achieved with styrenes in the presence of yttrium trichloride, BuLi, and diisobutylaluminium hydride (DIBAL-H) in THF. Alternatively, similar products were more simply prepared from pyridines and benzyl Grignard reagents. These reactions are not only a useful preparation of 4-substituted pyridines but are also complementary to other relevant reactions usually giving 2-substituted pyridines.

Subporphyrinato boron(III) hydrides.

Subporphyrinato boron(III) hydrides were prepared by reduction of subporphyrinato boron(III) methoxides with diisobutylaluminum hydride (DIBAL-H) in good yields. The authenticity of the B-H bond has been unambiguously confirmed by a (1)H NMR signal that appears as a broad quartet at -2.27 ppm with a large coupling constant with the central (11)B, characteristic B-H infrared stretching frequencies, and single crystal X-ray diffraction analysis. Red shifts in the corresponding absorption and fluorescence profiles are accounted for in terms of the electron-donating nature of the B-hydride. The hydridic character of subporphyrinato boron(III) hydrides has been demonstrated by the production of H2 via reaction with water or HCl, and controlled reductions of aromatic aldehydes and imines in the presence of a catalytic amount of Ph3C[B(C6F5)4].

Reduction of Weinreb amides to aldehydes under ambient conditions with magnesium borohydride reagents

Chloromagnesium dimethylaminoborohydride (ClMg+ [H3BNMe2]−, MgAB) is an analogue of the versatile lithium dialkylaminoborohydrides (LAB reagents), prepared by the reaction of dimethylamine-borane with methylmagnesium chloride. MgAB is a partial reducing agent for Weinreb amides under ambient conditions and is complementary to the commonly utilized lithium aluminum hydride (LiAlH4) and diisobutylaluminum hydride (DIBAL) reagents, while exhibiting enhanced chemoselectivity. To prevent over-reduction, the aldehyde products are readily isolated in good yields by forming the sodium bisulfite adducts. Aldehyde products can both be stored and later used as the bisulfite adducts, or can be regenerated from the bisulfite adducts by treatment with aqueous formaldehyde.

The first example of generation and emission of divalent Sm2+* ion in a liquid-phase chemiluminescence in the system SmCl3·6H2O–THF–Bui2AlH–O2

Abstract First it was found that the divalent Sm 2+ ion can act as enhancer and emitter of a liquid-phase chemiluminescence (СL) on the example of the near-infrared emission of Sm 2+* in the system SmCl 3 ·6H 2 O–THF–Bu i 2 AlH–O 2 . The Sm 2+* –CL ( λ max = 780 ± 20 nm) occurs upon adding the diisobutylaluminum hydride Bu i 2 AlH to a suspension of the SmCl 3 ·6H 2 O crystalline hydrate in THF. The Bu i 2 AlH removes water molecules from the coordination sphere of Sm 3+ and reduces Sm 3+ to Sm 2+ with formation of the SmCl 2 ·(THF) 2 complex. The excess of Bu i 2 AlH is oxidized by oxygen with generating a primary emitter, the triplet-excited molecule of isobutyric aldehyde 3 Me 2 CHC(H) = O * . The energy of the latter is transferred to the SmCl 2 ·(THF) 2 complex, leading to the formation of the excited state of the Sm 2+ ion. The composition of SmCl 2 ·(THF) 2 complex, which are formed after the interaction in the system SmCl 3 ·6H 2 O–THF–Bu i 2 AlH–O 2 , was also determined. Moreover, its photoluminescence (PL), UV–vis IR, 1 H and 13 C NMR spectra were measured. The spectrum of Sm 2+* –CL contains maxima both ions Sm 2+ and Sm 3+ due to incomplete reducing of Sm 3+ .

Alkylation of pyridines at their 4-positions with styrenes plus yttrium reagent or benzyl Grignard reagents.

A new regioselective alkylation of pyridines at their 4-position was achieved with styrenes in the presence of yttrium trichloride, BuLi, and diisobutylaluminium hydride (DIBAL-H) in THF. Alternatively, similar products were more simply prepared from pyridines and benzyl Grignard reagents. These reactions are not only a useful preparation of 4-substituted pyridines but are also complementary to other relevant reactions usually giving 2-substituted pyridines.