With Aluminum Hydrides

Lithium aluminum hydride (LAH) reductions are carried out in aprotic solvents and give rise to the dihydro- and tetrahydropyridine derivatives. LAH reacts with both pyridines and pyridinium salts. It has been known for some time that aged ( 24 h) pyridine and LAH solutions form complexes of lithium tetrakis(A -dihydropyridinyl)aluminate (40, LDPA), - which is believed to consist of a mixture of the 1,2- and 1,4-dihydropyridines (by NMR). Indeed, LDPA itself has been used as a selective reducing agent for ketones and affords 3-substituted pyridines (41) on reaction with alkyl halides. 2,5-Dihydropyridines have been identified as intermediates in similar reactions. Kuthan and co-workers have shown that for 3,5-dicyan- 

Kuthan, J. Prochazkova, and E. Janeckova, Collect. Czech. Chem. Commun. 33, 3558 (1968). 

The preference for a attack occurs due to the N-A1 interaction, aided by the metal orbitals from which hydride transfer can be considered as occurring favorably to these positions.  

Pentachloropyridine (44) gives mainly 2,3,6-trichloropyridine (45) on treatment with LAH at room temperature. - No products of ring reduction are observed, and the reactions are believed to proceed via an addition -elimination mechanism. The chlorine atom prevents additions at the 1,2 

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These reactions are also quite sensitive to steric factors, as shown by the fact that if 1-butene reacts with di(j iAisoamyl)borane the initially formed product is 99% substituted in the 1-position (15) compared to 93% for unsubstituted borane. Similarly, the product obtained from hydroformylation of isobutylene is about 97% isoamyl alcohol and 3% neopentyl alcohol (17). Reaction of isobutylene with aluminum hydride yields only triisobutjlaluininum. 

Temporary protection of the aldehyde function and reduction with aluminum hydride gave ( )-3-epigeissoschizal (275), from which silver oxide oxidation, followed by esterification, resulted in methyl ( )-epigeissoschizoate (277). 

Scheme 2.45 Reduction of propargylic electrophiles with aluminum hydrides. THP=tetrahydropyranyl.

Scheme 2.46 Synthesis of natural products by reduction of propargylic electrophiles with aluminum hydrides. DIBAH = diisobutylaluminum hydride ...

The carbaalanes [8, 9] possess clusters formed by aluminum and carbon atoms. They represent a new class of compounds which, in some respects, may be compared to the important class of carbaboranes. Usually, they were obtained by the reaction of aluminum alkynides with aluminum hydrides (hydroalumination) and the release of trialkylaluminum derivatives (condensation). The first carbaalane, (AlMe)g(CCH2Ph)5H 3 [10], was synthesized by the treatment of dimethylalumi-num phenylethynide with neat dimethylaluminum hydride. The idealized stoichiometric ratio of the components is given in Eq. (2), which also shows a schematic drawing of the molecular structure. Compound 3 was isolated in the form of colorless crystals in 60% yield. While 3 is only slightly air-sensitive, the less sterically shielded propynide derivative 4, also shown in Eq. (2), is highly pyrophoric [11],... 

Lithium hydride reacts with aluminum hydride forming lithium aluminum hydride, a powerful reducing agent ... 

Magnesium hydride forms double hydrides with aluminum hydride and boron hydride ... 

Metal Hydrides. Adding metal hydrides to olefins has been known many years. Some of these appear to be insertion reactions, i.e., olefin additions with aluminum hydrides (112), certain tin hydrides (98), certain germanium hydrides (77) mangesium hydride (76), boron hydride (//), and various transition metal hydrides. 

Only rare reports of the conversion of thiopyrones to thiopyrans are available. Unsubstituted 4-thiopyrone (335) was reduced with aluminum hydride to the corresponding 4-thiopyranol (2).5,90 A precipitate formed during the reaction of thiopyrone 336a with thionyl chloride was regarded to be a 4H-thiopyran derivative (336b).325... 

As AL is one of the most potent 3,4,5-trisubstituted phenethylamines yet described, and since the corresponding amphetamines are of yet greater potency, it would be a good guess that 4-allyloxy-3,5-dimethoxyamphetamine (3C-AL) would be an interesting compound to explore. It could be made from syringaldehyde in reaction with allyl iodide, followed by the formation of a nitrostyrene with nitroethane, followed by reduction with aluminum hydride. It is, as of the present time, both unsynthesized and unexplored. 

The 2-carbon analogue, 2C-2-TOET, was made from the same aldehyde intermediate. The appropriate nitrostyrene came smoothly from the aldehyde and nitromethane, and gave glistening pumpkin-orange crystals from methanol, that melted at 93-94 °C. Anal. (C12Hl5N03S) C,H. The final phenethylamine hydrochloride salt was prepared from its reduction with aluminum hydride in THF, and was isolated in the usual manner. It was a white crystalline mass that melted at 226-227 °C. It, as with the other 2-carbon analogues of the TOMs andTOETs, remains untasted as of the moment. 

The reduction of isoquinolinium ions has been extensively investigated with borohydride and aluminum hydride ions. The use of boro-hydride ion in a protonic solvent normally leads to the formation of 1,2,3,4-tetrahydroisoquinolines, whereas the reduction with aluminum hydride ion in an aprotic medium generally gives a 1,2-dihydroiso-quinoline. This 1,2-dihydroisoquinoline contains an enamine system and may undergo further reaction on treatment with acid. The 1,2-and 3,4-dihydroisoquinolines as well as isoquinolinium ions are reduced by the borohydride ion in a protonic medium to the 1,2,3,4-tetrahydroisoquinolines. 

The parent compound (5) may be prepared by heating o-xylylene dibromide (a,a -dibromo-o-xylene) with sodium or potassium sulfide, usually in aqueous ethanol (see Table I for references), or by reducing phthalic thioanhydride (Section VII, B) with aluminum hydride or diborane 20 the former procedure has been used to prepare a number of derivatives of 5 (Table I). Disodium o-xylylenedimercaptide (6) can be isolated from the reaction between o-xylylene dibromide and... 

The reduction of A-nitroso- to A-aminopiperazines is sometimes useful. Thus 1-methyl-4-nitrosopiperazine (35) afforded 4-methyl-l-piperazinamine (36) by refluxing with aluminum hydride in ether for 10 h (88% yield)449 or by treatment with zinc in acetic acid (>30% yield).1016, cf 982... 

Piperideines unsubstituted at the nitrogen atom may be prepared from the corresponding pyridine compounds by partial reduction with sodium and boiling alcohols (the Ladenburg reduction), by electrolytic reduction, or, preferably, by reduction with aluminum hydride. l-Alkyl-3-piperideines are prepared by reduction of quaternary pyridinium salts with formic acid (the Lukes reduction) or with complex hydrides. 

Reduction of a-fonnyl ketones. This reagent chemoselectively reduces the sodium salt of 1 to the or-hydroxymethyl ketone 1 Similar reductions have been clfcctcd with aluminum hydride (4, 233). 

Spira d.4imonaietraene (5). This elusive spiro compound has now been synthesized from the diacid chloride of diallylmalonic acid (I). This substance is treated in methylene chloride solution containing several mole equivalents of nitrotnethane with aluminum chloride at 25° to give, after hydrolysis with aqueous ammonium chloride, spiro[4.4]-nona-2,6-diene-l,5-dionc (2) in 51% yield. Reduction of (2) with aluminum hydride... 

An early claim (332, 334) to have prepared V(bipy)g+ has been revised (431) the compound V(bipy)3l is considered to be a mixture of V(bipy)3 and V(bipy) 3I2. The reaction of V(bipy ) or of Cr(bipy) + with aluminum hydride gives the neutral tris-bipyridyl complexes, but with other dipositive metals Al(bipy)3 is the major product (357). Attempts to prepare bipyridyl and plienanthroline derivatives of hexacarbonylvanadium led to the disproportionation of vanadium(O) (376). 

The results were interpreted in terms of steric requirements of the actual reducing species. It was suggested that attack of BH4" proceeds exclusively along the 1,4-reduction mode, whereas alkoxyborohy-drides (formed as reaction products) prefer the 1,2-reduction mode. The pyridine borine itself does not reduce enones under the reaction conditions, but it inhibits formation of alkoxyborohydrides. - The same trend was observed with aluminum hydride reductions. When LiAlH4 was first reacted with pyridine to form lithium tetrakis(dihydro-N-pyridyl)aluminate, 1,4-reduction predominated. ... 

Quinolines generally produce 1,2-dihydroqulnolines with aluminum hydrides. Diisobutylaluminum hydride and Red-Al have been used to reduce quinolines and quinoline-A -boranes (42 Scheme 9). The reactions are believed to proceed via aminoalanes or boranes and the dihydroquinolines produced are quenched and trapped as the carbamates by the addition of chloroformate esters. Minor amounts of 1,4-dihydro- and 1,2,3,4-tetrahydro-quinolines are also formed. The possession of a 2-substituent hinders reaction. At low temperatures the kinetic product, i.e. (43), is favored, but at higher temperatures reduction at the 4-position predominates which subsequently produces the tetrahydro derivative (44). A similar approach has been employed with isoquinoline, generating 1,2-disubstituted tetrahydroisoquinolines (45 Scheme 9). ... 

Scheme 75). The D/E ring system of these alkaloids has been constructed by the intramolecular [4 + 2]-cycloaddition of an oxadiene with an ot,P-unsaturated amide. Thermolysis of the diene 580 at 190°C in xylene produced a 4.5 1 mixture of the cis and trans- cycloadducts 581 and 582, respectively. They could be separated to provide cis-lactam (73%). Subsequent hydride reduction of 581 with aluminum hydride produced the tertiary amine 583. Acylation of 583 with trichloroacetyl chloride followed by a haloform cleavage gave the ester 584. Finally, hydrogenolysis of the iV-benzyl group provided the known bicyclic amine 585, which was previously converted to a mixture of 586 and 587. 

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