Tosylates lithium aluminum hydride

A solution of 3jS-hydroxy-5a-androstan-17-one tosylate (193, 60 mg) in tetrahydrofuran (10 ml, freshly distilled from lithium aluminum hydride) is added dropwise to a boiling suspension of lithium aluminum deuteride (60 mg) in tetrahydrofuran (10 ml). The resulting suspension is heated under reflux for 30 min and after cooling the excess reagent is decomposed by the careful addition of a few drops of water. The heating is continued for a few minutes to coagulate the inorganic salts which are removed by filtration... 

In a more general sense, this reduction method provides a convenient pathway for converting an aromatic carboxyl group to a methyl group (see Table I).7 Previously, this transformation has been achieved by reduction of the acid to the alcohol with lithium aluminum hydride, conversion of the alcohol to the tosylate, and a second reduction either with lithium aluminum hydride [Aluminate(l —), tetrahydro, lithium,... 

Redaction of / -toluenesulfonyIhydrazides by complex hydrides yidds hydrocarbons. The TV -tosyl hydrazide of stearic acid gave a 50-60% yield of octa-decane on reduction with lithium aluminum hydride [577]. 

Neopentyl sulfides have been prepared by alkylation of sodium sulfide with neopentyl tosylate in high-boiling polar solvents,4,5 or in low yields by reduction of alkyl 2,2-dimethylpropanethioate with the combination of lithium aluminum hydride and a large excess of boron trifluoride-etherate. ... 

Attempts to synthesize C-terminal peptide aldehydes using other reductive techniques are less successful. 24"29 The reduction of a-amino acid esters with sodium amalgam and lithium aluminum hydride reduction of tosylated a-aminoacyldimethylpyrazoles resulted in poor yields. 26,29 The Rosemond reduction of TV-phthaloyl amino acid chlorides is inconvenient because the aldehyde is sensitive to hydrazine hydrate that is used to remove the phthaloyl group. 27 28 jV -Z-Protected a-aminoacylimidazoles, which are reduced to the corresponding aldehydes using lithium aluminum hydride, are extremely moisture sensitive and readily decomposed. 25 The catalytic reduction of mixed carbonic/carboxylic acid anhydrides, prepared from acylated a-amino acids, leads to poor reproducibility and low yields. 24 The major problems associated with these techniques are overreduction, racemization, and poor yields. 

Horner-Emmons reaction of N-terminal blocked aldehyde 1 with sulfonylphosphonates in the presence of sodium hydride gives the amino acid vinyl sulfone 2, which is deprotected with acid and converted into its chloride or tosylate salt 3 and coupled by the mixed anhydride method with an N-terminal protected peptide or amino acid to give the desired peptide vinyl sulfones 4 (Scheme 2). 4 5 N-Terminal protected aldehydes 1 are obtained from reduction of Boc amino acid V-methoxy-A-methylamides (Weinreb amides, see Section 15.1.1) by lithium aluminum hydride. 9 The V-methoxy-V-methylamide derivatives are prepared by reaction of Boc amino acids with N,O-dimethylhydroxylamine hydrochloride in... 

After decarboxylation, enolization in the alternative mode would cause racemization. However, this reasoning does not explain why 199 was racemized. The racemic a-aminoketones were eventually resolved via their bromocamphorsulfonates. Optically pure (—)-indolizidin-l-one (196) was reduced with lithium aluminum hydride to the alcohol, tosylated, and again reduced to (+)-indolizidine [Eq. (28)]. Since indolizidine obtained from R-pipecolic acid [Eq. (29)] was levorotatory, it followed that the absolute configuration of the original ketone was S.254 The optical rotatory dispersion (ORD) curve of the S(-)-ketone showed a strong negative Cotton effect as predicted by the octant rule. 

Treatment of methyl 2,3-anhydro-4,6-di-0-tosyl-a-D-alloside with a boiling solution of lithium aluminum hydride in tetrahydrofuran for only one hour affords291 methyl 4-0-tosyl-a-D-digitoxoside, by simultaneous opening of the anhydro-ring (at carbon atoms 2 and 3) and detosyloxylation at carbon atom 6 ... 

Lithium aluminum hydride Methyl chloroformate Tosyl chloride Diazomethane Palladium on carbon Methyl mercaptan... 

Formation and Reduction of Nitriles Like the azide ion, cyanide ion (- C=N ) is a good Sn2 nucleophile it displaces leaving groups from unhindered primary and secondary alkyl halides and tosylates. The product is a nitrile (R—C=N), which has no tendency to react further. Nitriles are reduced to primary amines by lithium aluminum hydride or by catalytic hydrogenation. 

Voacanginol could be tosylated without quaternization occurring (cf. iboxygaine, Section I, A), and the resulting sulfonate with lithium aluminum hydride afforded 18-methylibogaine, mp 189°-190° (32). 

Second, direct chemical proof of the aspidospermine skeleton was obtained by conversion of spegazzinidine dimethyl ether (LXX) to its tosylate (LXXIV) which on reduction with lithium aluminum hydride gave (— )-JVft-deacetyl-Xa-ethylpyrifolidine (LVII) identical, except for direction of rotation, with the product, (+ J-Xa-deacetyl- -ethyl-pyrifolidine (LVII), obtained by a similar reduction of (+ )-pyrifolidine (XLVI). Since (+ )-pyrifolidine is antipodal to aspidospermine (Section II, K), spegazzinidine has the same absolute configuration as aspidospermine (36). 

The stereochemistry at positions 3,15, and 20 is preserved in alloyo-himbone (LXIV) and its reduction product, alloyohimbane (3a, 15a,20a-yohimbane, LXV), of which several syntheses have been reported (Volume VII, p. 58) (30). In a recent synthesis, tryptamine (XXVI) was condensed with 4-methoxyhomophthalic anhydride (LXVI) to the amide LXVII. This in the five stages shown was converted to LXVIII and the latter, through another series of reactions, converted to LXX consisting of two epimers which were separable. Tosylation of the hydroxyl and ultimate reduction with lithium aluminum hydride generated alloyohimbane (LXV) (31). 

Derivatives of 1-methyl-3//-l,4-benzodiazepine-2,5(l/I,4/I)dione (193) were synthesized by ring closure of substituted 2-(A-chloro-acetyl-A-methylaminoJbenzamides with sodium methoxide in methanol.209 Treatment of 193 with lithium aluminum hydride led to reduction of both carbonyl groups.209 The parent tetrahydro system (194) has been prepared by reaction of the tosylate (195) with 1,2-dibromoethane followed by hydrolysis.210 The preparation of 194 by another route had previously been noted.204 Reaction of 194 with formaldehyde or benzaldehyde gave a compound formulated as 196 (R = H or C6H5).210 Hydrolysis of 196 (R = C6H5) with 0.1 N hydrochloric acid gave 194 while 196 (R = H) was not hydrolyzed at this acidity. 

Mesylates are less reactive toward solvolysis than the corresponding tosylates. Mesylates are better suited to reduction by lithium aluminum hydride than tosylates (1, 58) because the mesylate fragment is reduced to methyl mercaptan, which is easily removed. 

Reduction of l,4-diacetyl-5,6-diphenyl-l,2,3,4-tetrahydropyrazine with lithium aluminum hydride formed l,4-diethyl-5,6-diphenyl-l,2,3,4-tetrahydropyrazine (1562). Both l,4-dibenzenesulfonyl-2-hydroxy-l,2,3,4-tetrahydropyrazine and l,4-dibenzenesulfonyl-2,5-dihydroxypiperazine reacted with hot acidic methanol to produce l,4-dibenzenesulfonyl-2-methoxy-l,2,3,4-tetrahydropyrazine (1602). The tosyl analogue behaved similarly. Reaction of 2-hydroxy-l,4-ditosyl-l,2,3,4-tetrahydropyrazine (73, X = OH) with benzenethiol in acidified acetone gave 2-phenylthio-l,4-ditosyl-l,2,3,4-tetrahydropyrazine (73, X = SPh) (1602). 

Hydrolysis of 3-ethoxycarbonylpiperazine-2,5-dione gave 3-carboxypiperazine-2,5-dione (p Tj 2.5) (1722) and 3-ethoxycarbonylpiperazine-2,5-dione with primary and secondary amines gave the expected amides (1722). 2-Hydroxyiminopiperazine with benzoyl chloride gave the dibenzoyl derivative (146) and with tosyl chloride gave a tritosyl derivative (147) (926). Reduction of 3-phenylpiperazin-2-one with lithium aluminum hydride gave 2-phenylpiperazine, also obtained by similar reduction of 3-phenylpiperazine-2,6-dione (1612). 

The ability of reducing agents, such as lithium aluminum hydride, to reduce halides and sulfonates to their corresponding alkyl derivatives is well known. Lithium aluminum hydride is also selective for the reduction of primary halides and sulfonates over secondary analogs. As shown in Scheme 6.70, this reaction was applied to a bis-tosylate with the major isolated product being the mono-tosylate with deoxygenation at C-6 [109]. 

The correlation of cytisine with (— )-anagyrine (IX) was achieved by permanganate oxidation of the latter followed by lithium aluminum hydride reduction, tosylation to XV of the reduction product, dehydrogenation with mercuric acetate, and final hydrogenation to the epimeric tosylate ([a]ff +10°) (XVI). The same compound ([a]if -1-9.8°) was obtained by tosylating the reduction product, (+ )-desoxotetrahydro-cytisine (VII), of cytisine (VIII). Table II shows the absolute configuration of several alkaloids. 

Dihydroxylation of the stilbene double bond in the trans isomers of Combretastatin A-1 and A-4 produced diols which by treatment with boron trifluoride in ethyl ether [44] or with trifluoroacetic acid [17] resulted in pinacolic rearrangement to produce an aldehyde. The aldehyde was converted in a variety of derivatives, as illustrated in the Scheme 20, via the following reaction sequence reduction with sodium borohydride to primary alcohol which was derivatized to the corresponding mesylate or tosylate, substitution with sodium azide and final reduction to amine with lithium aluminum hydride. Alternatively the aldehyde was converted to oxime which was catalitically hydrogenated to amine [17]. 

Halides and tosylates. Trevoy and W. G. Brown found that lithium aluminum hydride reduces benzyl iodide and benzyl bromide in high yield at 35° in either diethyl ether or tetrahydrofurane. In tetrahydrofurane at 65°, benzyl chloride and 1 -bromodecane are reduced to toluene and to n-decane, both in 72% yield. Johnson, Blizzard, and Carhart found that lithium aluminum hydride reacts more sluggishly than in other reductions and presented experimental evidence that not all four hydrogen atoms possess adquate reactivity toward alkyl halides. Thus the reaction probably proceeds in at least two steps, the first of which is much more rapid than... 

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