Lithium aluminium hydride reduction

Hydroxyalkylthiazoles are also obtained by cyclization or from alkoxyalkyl-thiazoles by hydrolysis (36, 44, 45, 52, 55-57) and by lithium aluminium hydride reduction of the esters of thiazolecarboxylic acids (58-60) or of the thiazoleacetic adds. The Cannizzaro reaction of 4-thiazolealdehyde gives 4-(hydroxymethyl)-thiazole (53). The main reactions of hydroxyalkyl thiazoles are the synthesis of halogenated derivatives by the action of hydrobroraic acid (55, 61-63), thionyl chloride (44, 45, 63-66), phosphoryl chloride (52, 62, 67), phosphorus penta-chloride (58), tribromide (38, 68), esterification (58, 68-71), and elimination that leads to the alkenylthiazoles (49, 72). 

However, examples of the failure of thioketals to survive lithium aluminium hydride reduction have been reported (see ref. 134). 

J.M. Lalancette et al., Reduction of Functional Groups with Sulfurated Borohydrides, Synthesis 1972, 526. J. Malek u. M. Cerny, Reduction of Organic Compounds by Alkoxyaluminohydrides, Synthesis 1972, 217. S.-C. Chen, Molecular Rearrangements in Lithium Aluminium Hydride Reduction, Synthesis 1974, 691. 

In the synthesis of methyl corydalate (55) Nonaka et al. (65) used the methiodide of (-t-)-tetrahydrocorysamine (65) as substrate and the Hofmann degradation method for ring opening (Scheme 16). The methine base (66) on hydroboration afforded alcohol 67, identical with a product obtained from 55 by lithium aluminium hydride reduction. 

Estradiol is formed by lithium aluminium hydride reduction of the ketone. We can formulate this simply as hydride acting as the nucleophile, though hydride delivery by LAH is strictly more complex than this. Unless you are specifically asked for details, treat LAH as a source of hydride ion. 

These intermediates were used to synthesize optically pure ephedrines and amphetamines without recourse to resolution, since the chirality of the amino acid educt was entirely conserved throughout the process. The reduction of (S)-2-(ethoxycarbo-nyl)amino-propiophenone (74) first produced a mixture of alcohols (75a, b) Lithium aluminium hydride reduction then produced the desired secondary amino alcohols (76a, b). Table 1 illustrates the reduction scheme and the diastereomer ratios obtained "K... 

Studies in stereochemistry. VII. Molecular rearrangements during lithium aluminium hydride reductions in the 3-phenyl-2-butanol series. J. Amer. chem. Soc. 74, 2149 (1952). 

Lithium, use of, 931 Lithium aluminium hydride, reductions with, 877-881... 

A related strategy was used to prepare D-allosamine (134). Cycloaddition of the dipole derived from nitroacetal (129) to (S )-vinyl dioxolane (74) afforded a mixture of erythro/threo isoxazolines 130 131 (Scheme 6.72). The erythro isoxazoline was subjected to hydroxylation as described above, to give 4-hydroxyisoxazoline 132 with high diastereoselectivity. Lithium aluminium hydride reduction furnished a single diastereomer of aminodiol 133, which could be deprotected to give the hydrochloride salt of D-allosamine (134) (141). 

Generally, however, lithium aluminium hydride reduction is used to convert isatins to indoles. Thus, 4,5,6-trimethoxyisatin,251 5-bromo-isatin,252 5-chloro-6-methoxy-l-methylisatin,253 1-ethyl- and 1-methyl-isatin,254 and 4,6-dimethoxyisatin94 all gave the corresponding indoles. 

Any rigorous study of the oxidation of polymeric organolithium compounds should consider these products and their variation in yield with reaction conditions. To date, few of these reaction products have been considered, let alone identified and analyzed. However, the presence of the macroperoxide has been identified recently among the products of the oxidation of poly(styryl)lithium 352). Lithium aluminium hydride reduction followed by SEC analysis of the dimer fraction before and after reduction... 

Sn—H bond-containing stannaindenes (91) are accessible by lithium aluminium hydride reduction of the monochloro derivative (equation 36)103. 

Only a few examples will be reported here (for a more complete survey, see refs. 47-53). Bllchi and co-workers (54) have shown that lithium aluminium hydride reduction of the tosylate 142 gave specifically the ring contracted product J44 via the methyl ketone 143. 

Dihydromethanobenzodioxepin 155 was obtained by alkylation of benzofuranone 153 and lithium aluminium hydride reduction together with tetrahydrofurobenzofuran 154 (Scheme 42). The ring expansion to 155 probably proceeds via hemiacetal 156 <2005JOC6171>. 

Note. (1) 2-Benzyl-1,3-dibromopropane may be prepared from diethyl benzyl-malonate (Expt 5.132), by lithium aluminium hydride reduction to give 2-benzyl-propane-1,3-diol (for conditions compare Expt 5.38), and subsequent conversion into the dibromo derivative using the conditions described in Expt 5.54 as a guide. 

Lithium aluminium hydride reduction of 235 followed by mesylation afforded 236. The latter was oxidized with osmium tetroxide and sodium metaperiodate to yield the cyclobutanone 237. Treatment of 237 with acid afforded in 48% yield the ketoacid (238), which was esterified with diazomethane to 239. The latter was converted to the ketal 240 by treatment with ethylene glycol and /7-toluenesulfonic acid. Compound 240 was reduced with lithium aluminium hydride to the alcohol 241. This alcohol had been synthesized previously by Nagata and co-workers (164) by an entirely different route. The azide 242 was prepared in 80% yield by mesylation of 241 and treatment of the product with sodium azide. Lithium aluminium hydride reduction of 242 gave the primary amine, which was converted to the urethane 243 by treatment with ethyl chloroformate. The ketal group of 243 was removed by acidic hydrolysis and the resulting ketone was nitro-sated with N204 and sodium acetate. Decomposition of the nitrosourethane with sodium ethoxide in refluxing ethanol afforded the ketone 244 in 65% yield. The latter had been also synthesized previously by Japanese chemists (165). The ketone 244 was converted to the ketal 246 and the latter to 247... 

The mixture 258 was converted to the unstable benzenesulfonyl aziridine 259 by treatment with an excess of benzenesulfonyl azide in benzene. Ace-tolysis of 259 with acetic acid and sodium acetate at room temperature for several days afforded the crystalline mixture of diastereoisomers represented by the formula 260. The aziridine rearrangement was regiospecific and 260 was the only product detected during this rearrangement. Lithium aluminium hydride reduction of 260 followed by acetylation yielded the mixture 261 in 85% yield. Selective hydrolysis of 261 afforded 262 in quantitative yield. The diastereoisomeric mixture 262 was converted into the diols 263 by hydrogenolysis. The diol mixture was oxidized with chromium trioxide... 

Lithium aluminium hydride reduction of lucidusculine (35) afforded napelline (34) in quantitative yield. Napelline was hydrogenated with platinum oxide in acetic acid to afford dihydronapelline (286). Treatment of 286 with mercuric acetate in aqueous acetic acid followed by oxidation with chromium trioxide in pyridine afforded 287 in 16.5% yield. Ketalization of 287 yielded 285 in a yield of 71%. On refluxing 285 with methanolic base, a 4 6 equilibrium mixture of 285 and 288 was obtained. These compounds... 

Compound 258 was prepared according to the procedure described during the synthesis of napelline in Section VIII,B. The hydroxyl group of 258 was removed by mesylation and subsequent lithium aluminium hydride reduction to give 297. The latter was converted to the pentacyclic aromatic intermediate 298 using a reaction sequence employed for the synthesis 169)... 

The lactone ring of dimethylodecodine (14) was cleaved by lithium aluminium hydride reduction to the corresponding diol. The same diol was formed from the lithium aluminium hydride reduction of the hydroxyester prepared from the product of alkaline hydrolysis (17). 

The presence of a methylene bridge between a hydroxyl and an amine group of lythramine was confirmed by lithium aluminium hydride reduction of O-methyldeacetyllythramine (75) to /V,0-dimethyllythranidine (77) (7). 

Lythrancine-type alkaloids have a hydroxyl or an acetoxyl group at carbons 3, 4, and 11. Lythrancines 100-103 and lythrancines 104, 105, and 106 are epimeric at C-3. Lythrancepines 107, 108, and 109 are C-4 deoxy derivatives of lythrancines I-IV. This was demonstrated by lithium aluminium hydride reduction of the O-tosylate of lythrancine 102 and acetylation of the product to lythrancepine 109 and its C-3 epimer. 

Since the hemiacetal 3, can now readily be prepared from cheap commercially available starting materials (vide supra, Eq. (1))7), this reaction constitutes a convenient source of 1-vinylcyclopropanols. Otherwise, the 1-ethynyl-cyclopropanols 9, also easily available from 3 or from its magnesium salt 10 (vide supra, Eq. (4) and (6) underwent either lithium aluminium hydride reduction in refluxing THF to lead exclusively to the E-1-vinylcyclopropanols 69 or reduction with dicyclopentadienyl-titanium hydride in ether at 0.°C, prepared from isobutylmagnesium halides and a catalytic amount of dicyclopentadienyl titanium dichloride (r -CjH TiCk), to yield exclusively the Z isomer 70, Eq. (22) 15,39). 

Lithium aluminium hydride reduction of 1,2-disubstituted cyclopropene-3-carboxy-lates occurs initially at the ester group, but with additional reagent good yields of cis-1,2-disubstituted-rranj-3-methanols are obtained 176). The reduction of the double bond is regioselective, leading to the more stable carbanion, and the attack of the hydride ion exclusively cis to the 3-substituent may be explained in terms of initial formation of an alkoxyaluminium complex followed by intramolecular hydride transfer 176). In the case of cyclopropene-1-carboxylates, direct reduction to the saturated alcohol occurs thus (253) is converted to the rranj-alcohol177) ... 

The n.m.r. characteristics of the isopropylidene acetals of the four possible types of ring A primary, secondary 1,3-glycol systems, exemplified by serratriol (178), lycoclavanol (179), methyl hederagenate (180), and methyl 3-epihederagenate (181), have been tabulated, and provide a useful means of differentiation.132 The reactions of the primary monotosylates of these four types provide further confirmation of stereochemistry.133 With potassium t-butoxide the cis types (178) and (181) afforded oxetans whereas the trans types (179) and (180) were converted into A-seco-aldehydes (182). Appreciable amounts of alkyl oxygen fission products were obtained on lithium aluminium hydride reduction of the monotosylates of (178), (180), and (181), presumably via participation of the 3-hydroxy-group, e.g. (183). 

The compound (70) by epoxide ring-opening with hydrogen fluoride, followed by photocatalysed addition of acetylene to the A16-bond and lithium aluminium hydride reduction, gave (71). Protection of the 1,2-diol system in (71) as the acetonide followed by oxidation, dehydration, and regeneration of the diol grouping produced... 

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