Aluminum hydride-triethylamine

A solution of hydrazoic acid (prepared from about 30 g sodium azide) in ca. 200 ml chloroform is prepared in a well-ventilated hood. Cholesterol (15 g) is dissolved in the hydrazoic acid solution and 3.5 ml of triethylamine is added. The reaction mixture is then stirred at room temperature while 7 g of A-chlorosuccinimide is added. The reaction mixture is allowed to stand overnight and then the chloroform solution is washed successively with dilute sodium bisulfite, dilute soldium bicarbonate solutions and finally with water. The chloroform extract is then dried (Na2S04) and the solvent removed in vacuo. The residue is crystallized from ethanol to yield ca. 8.5 g of (101) in colorless needles mp 138-139°. The chloro azide is reduced to the aziridine by lithium aluminum hydride according to the foregoing procedure. 

Reduction of the 5A/-2-benzazepin-5-one 5, prepared by base-catalyzed (triethylamine) dehydrobromination of4-bromo-8-chloro-l-(2-chlorophenyl)-3//-2-benzazepin-5(4//)-one, with lithium aluminum hydride at — 78 C yields a mixture of the 5//-azepin-5-ol 6 and the dihydrobenz-azepinone 7.78 Attempts to prepare the 5-bromo derivative from the alcohol 6 failed. 

Triethylamine was distilled from lithium aluminum hydride. 

Intramolecular nitrile oxide—olefin cycloaddition of oxazolidine and thiazoli-dine oximes 407 (R = H, Me R1 =H, Me X = 0, S n = 1,2) proceed stereose-lectively, yielding tricyclic fused pyrrolidines and piperidines. Thus, 407 (n =2 R = H R1 =Me X=S) has been oxidized to the nitrile oxides with sodium hypochlorite, in the presence of triethylamine in methylene chloride, to give the isoxazolothiazolopyridine 408 in 68% yield. Reduction of 408 with lithium aluminum hydride affords mercaptomethylmethylpiperidine 409 in 24% yield (448). 

Triethylamine was fractionally distilled from lithium aluminum hydride under nitrogen and acryloyl chloride was distilled under nitrogen. 1,1,2-Trichlorotrifluoroethane (Freon 113) was distilled from phosphorus pentoxide under nitrogen. Azobisisobutyronitrile (AIBN) was used as received. Methyl ethyl ketone peroxide (MEKP) (9% Organic Peroxide VN 2550) was obtained from Witco. Alumina (neutral, Brockman activity 1, 80-200 mesh) was obtained from Fisher Scientific Co. All reagents were obtained from Aldrich unless otherwise specified. 

Dichloromethane and triethylamine were distilled from calcium hydride before use. Silica gel 60. 0.040-0.063 mm (Merck) was used for column choromatography. Lithium aluminum hydride (95%, powder) was obtained from Aldrich Chemical Co., Inc. 

In view of the multicomponent nature of the tandem [4 + 2] / [3 + 2] cycloaddition, the potential for a combinatorial approach to the synthesis of nitroso acetals has been investigated on solid-phase supports. The incorporation of either the dipolarophile or the starting nitroalkene on a Wang-type resin is compatible with the tandem cycloaddition promoted at high pressures (Schemes 2.28 and 2.29). The solid-supported nitroso acetals are subsequently liberated (in moderate yields from the staring nitroalkene) upon the addition of a catalytic amount of potassium cyanide in triethylamine and methanol or by reduction with lithium aluminum hydride (LAH) (261,264). 

The methyl group was introduced by a two-step procedure. Thus, the hydrazone Michael adducts 52 were converted into the enol pivaloates 53 in excellent yields and diastereomeric excesses de > 96%) by treatment with pivaloyl chloride and triethylamine. After treatment with lithium dimethylcuprate the chiral auxiliary was removed by addition of 6n HCl in order to obtain the 5-substituted 2-methylcyclopentene carboxylate 54 in good yields and with excellent stereoselectivity (de, ee > 96%). Finally, the asymmetric synthesis of dehydroiridodiol (55, R = Me, = H) and its analogues was accomplished by reduction of 54 with lithium aluminum hydride or L-selectride leading to the desired products in excellent yields, diastereo- and enantiomeric excesses (de, ee > 96%). 

Typical imine reactivity is also displayed in 1//-1,2-diazepines which react with phthaloyl acetyl chloride in the presence of triethylamine to give a / -lactam fused system (76H(5)47l). 1H-2,3-Dihydro-l,2-benzodiazepines, obtained by the lithium aluminum hydride... 

Perhydropyrido[l,2-a]pyrimidine (282) can be converted in an acetic anhydride-formic acid mixture to the 1-formyl derivative, and the 1-formyl group can be reduced to the methyl group with lithium aluminum hydride.342 Treatment with ethylene oxide in the presence of sodium hydroxide leads to the l-(2-hydroxyethyl) derivative,342 and heating with diethylaminoethyl chloride in acetone in the presence of triethylamine gives the l-(2-diethyl-aminoethyl)perhydropyrido [ l,2- ]pyrimidine.27 6,27 7... 

Preparation of Derivatives. Enoate derivatives are prepared from the corresponding chiral alcohol by treatment with acry-loyl chloride in the presence of Triethylamine and catalytic 4-Dimethylaminopyridine or the appropriate carboxylic acid chloride and Silveril) Cyanide. Alkynyl ethers are readily available from the potassium alkoxide by treating with Trichloroethylene, in situ dechlorination with n-Butyllithium, and electrophilic trapping. Trapping the intermediate anion with a proton source or lodomethane followed by Lindlar reduction of the alkynyl ether affords the corresponding vinyl and l-(Z)-propenyl ether, respectively, while reduction of the alkynyl ether with Lithium Aluminum Hydride affords the l-( )-propenyl ether. 

Later, this cycloaddition reaction was improved by the pretreatment of the enamide ester with an equimoler amount of trialkylsilyl trifluoromethanesul-fonate and triethylamine at ambient temperature. The synthesis of tyro-phorine (119) was achieved by the above improved method (Scheme 55). The enamide ester 441 was subjected to annulation using t-butyldimethylsilyl triflate and triethylamine at 15°C to produce the bicyclic lactam 442 in 68% yield. Oxidation of 442 with thallium(III) trifluoroacetate and boron triflu-oroetherate in a mixture of dichloromethane and trifluoroacetic acid at 4°C produced (83%) the pentacyclic compound 443. Hydrolysis of 443, followed by decarboxylation of the resultant acid, gave the pentacyclic lactam 444. Reduction of 444 with sodium bis(2-methoxyethoxy)aluminum hydride in refluxing dioxane afforded tyrophorine (119) (85CC1159). 

A more recent examination of P. nanus revealed the presence of a new base, piptanthine, C20H35N3 (mp 143°) (124). Piptanthine (CLVIII) reacts with formaldehyde to form homopiptanthine (CLXI) (mp 189°) which suffers hydrolysis to its progenition on acid treatment. With phosgene, or less satisfactorily with ethyl chloroformate, in the presence of triethylamine there is formed homoxypiptanthine (CLX) (mp 155°). Lithium aluminum hydride reduction of the latter gives homopiptanthine. 

An aldehyde synthesis utilizing ethylenimine is illustrated by the following example. Reaction of cyclopropanecarboxylic acid chloride with ethylenimine and triethylamine in ether at 0° gives a precipitate of triethylamine hydrochloride and a solution of the 1-acylaziridine (3), which is reduced by lithium aluminum hydride... 

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