Lithium aluminium hydride adducts

This method is very useful for the construction of 1-substituted 3,4-dihydroisoquinolines, which if necessary can be oxidized to isoquinolines. A P-phenylethylamine (l-amino-2-phenylethane) is the starting material, and this is usually preformed by reacting an aromatic aldehyde with nitromethane in the presence of sodium methoxide, and allowing the adduct to eliminate methanol and give a P-nitrostyrene (l-nitro-2-phenylethene) (Scheme 3.17). This product is then reduced to the p-phenylethylamine, commonly by the action of lithium aluminium hydride. Once prepared, the p-phenylethylamine is reacted with an acyl chloride and a base to give the corresponding amide (R = H) and then this is cyclized to a 3,4-dihydro-isoquinoline by treatment with either phosphorus pentoxide or phosphorus oxychloride (Scheme 3.18). Finally, aromatization is accomplished by heating the 3,4-dihydroisoquinoline over palladium on charcoal. 

Subsequent cleavage of the resin-bound Diels-Alder adducts employing lithium aluminium hydride (LiAlH4) via a traceless linker strategy afforded the cyclic phenylethy-lamines. Alternatively, selective reduction of the nitro group using tin(II) chloride... 

A further example of this general type of reaction is provided by the synthesis of cyclooctene sulphide (6).4 Here an alkene is converted into an adduct with succinimide-A-sulphenyl chloride (reaction formulated in full in Expt 8.3), which is reduced with lithium aluminium hydride at — 78 °C to form the product. 

The foregoing adduct (9.4 g, 0.034 mol) is dry tetrahydrofuran (25 ml) is added dropwise to a stirred suspension of lithium aluminium hydride (1.1 g) in tetrahydrofuran (10 ml) at — 78 °C under nitrogen. After stirring for 10 minutes, the mixture is allowed to warm to room temperature and then quenched with water. The episulphide is extracted with ether and, after drying over magnesium sulphate, the solvent is removed and the residue distilled under reduced pressure to afford cyclooctene sulphide (4.7 g, 97.35%), b.p. 50 °C/2 mmHg. 

Four new pseudo-sugars having ce-ido, a-manno, P-altro and P-manno configurations have been synthesized from the Diels-Alder adduct 33 by the following method. Bromolactonization of 33 with hypobromous acid gave 2-e.w-bromo-4,8-dioxatri-cyclo[4.2.1.03,7]nonan-5-one (38). Reduction of 38 with lithium aluminium hydride,... 

Epoxidation of the adduct (265) gave a mixture of the la,2a- and 1/3,2/3-epoxides in the ratio 2 3, separable by silica gel chromatography. Lithium aluminium hydride reduction of the la,2a-epoxide afforded la-hydroxy-7-dehydrocholesterol. 

An improved route to 2a-hydroxycholesterol has been devised as part of the preparation of 2a-hydroxy-vitamin D3 (263 R1 = R4 = R5 = R6 = H, R2 = R3 = OH).123 Hydroxylation of the A bond of cholesta-l,5-dien-3/3-ol by means of 9-borabicyclo[3,3,l]nonane followed by reaction with alkaline hydrogen peroxide produced the 2-equatorial 2a,3a-diol in 70—80% yield. The conventional four-step sequence, acetylation, bromination, dehydrobromination, and hydrolysis, gave 2a -hydroxycholesta-5,7-dien-3/3-ol which was converted into 2a-hydroxy-vitamin D3. The isomeric 2/3-hydroxy-vitamin D3 has also been reported.124 Reaction of the 1/6,2/3-oxide obtained by peroxidation of the adduct (265) with lithium aluminium hydride results in a mixture of 2/3,3/3-dihydroxycholest-5,7-diene and its 1/3,3/3-dihydroxy-epimer in the ratio 8 1. Irradiation of the former 5,7-diene furnished the expected previtamin, which on equilibration gave 2/3-hydroxy-vitamin D3 (263 R1 = R4 = R5 = R6 = H, R2 = a-OH, R3 = OH). 

Treatment of enamines with a,/ -unsaturated esters yields Michael adducts 189, which undergo reductive cyclization with lithium aluminium hydride to tetrahydropyrans 190. Elimination of the secondary amine moiety then affords dihydropyrans 191 (equation 81)102. 

The reduction of the maleic anhydride adduct (303) with lithium aluminium hydride was previously reported to occur selectively to give the lactone (304). The lower selectivity now observed with sodium aluminium hydride (none at all with sodium borohydride) is interpreted as evidence for a complex (305) of the ester and anhydride carbonyl groups with a solvated lithium ion when lithium aluminium hydride is used, leading to selective reduction of the free carbonyl group.Sodium ions are considered not to form so stable a complex. 

For the synthesis of (69), the enol ether (71) from the indanone (70) was carboxylated with COa-n-butyl-Iithium in THF at —70 C to yield (72). The methyl ester (73) was converted into (75) via the maleic anhydride adduct (74), essentially as described in earlier work. Lithium aluminium hydride reduction followed by oxidation with dicyclohexylcarbodi-imide afforded the aldehyde (76). This was condensed with excess (77) to yield a mixture of the diastereomers (78). Oxidation with chromium trioxide-pyridine in methylene dichloride gave (79), which could be converted into the diketone (80) by treatment with excess benzenesulphonylazide. The diketo-lactam (81) was prepared from (80) as described for the synthesis of the analogous intermediate used in the synthesis of napelline. Reduction of (81) with lithium tri-t butoxyaluminohydride gave the desired dihydroxy-lactam (82). Methylation of (82) with methyl iodide-sodium hydride gave (83). Reduction of this lactam to the amine (84) with lithium aluminium hydride, followed by oxidation with potassium permanganate in acetic acid, gave (69). 

Sulfenic acids, esters and halides are reduced to thiols by many reagents, e.g. hydrazine, lithium aluminium hydride and metallic sodium. These addition reactions are extensively employed for trapping sulfenic acids, e.g. with ethyl acrylate (57) to give the adduct (58) (Scheme 32). 

The carbonyl adducts of allyl phosphine oxides, e. g., 24 and 29 can also be used to make allyl alcohols32 by the reductive removal of the Ph2PO group with lithium aluminium hydride a reaction involving transposition of the double bond, e. g., 24 36. In this approach, the allyl anion of 23 is a reagent for the vinyl anion synthon 37. 

The diethyl ester derived from the Diels-Alder adduct of thebaine with maleic anhydride has been converted into the lactone (124), by methylmagnesium iodide, and into a diol by lithium aluminium hydride. The diol has been dehydrated to the diene (125), which undergoes Diels-Alder addition of N-phenylmaleimide to give the adduct (126). °... 

Ergosta-5,7,22,24(28)-tetraen-3jS-ol has been synthesised from ergosterol by ozonolysis to the 22-aldehyde and construction of the appropriate side-chain using a Wittig reaction. During these reactions, the 5,7-diene system was protected as the Diels-Alder adduct (546) with 4-phenyl-l,2,4-triazolin-3,5-dione, from which the homoannular diene could be regenerated in 99 % yield by reduction with lithium aluminium hydride. 

A synthesis10 (Scheme 3) of ( )-elaeocarpidine avoids the production of dihydroelaeocarpidine during lithium aluminium hydride treatment of the intermediate (5) by reduction, using low temperatures, in the presence of pyrrolidine it is considered that the secondary amine traps the partially reduced amide in the form of an N(4)-C(20)—NC4H8 adduct until hydrolytic work-up breaks the N—C—N systems and allows cyclization to proceed. 

Treatment of solutions of lithium aluminium hydride in ether with the hydrochloride salts of bulky trialkylphosphines provides a route to stable tertiary phosphine adducts of alane, AlH,." ... 

The thermal extrusion of sulphur dioxide from sulphones and sulpholene adducts is a well known procedure for producing 1,3- or 1,4-dienes and skipped polyenes. Lithium aluminium hydride has now been shown to effect this extrusion in good yield under mild conditions (refluxing ether)." The technique is similar to, but apparently mechanistically different from, the LiAlH4-promoted retro-Diels-Alder reaction of triazolinedione adducts reported recently by Barton. 

Preparation.—Alcohols can be obtained from terminal alkenes by hydro-alumination with lithium aluminium hydride in the presence of a titanium complex, followed by oxidative cleavage of the adduct (Scheme 1). The sequence provides anti-Markovnikov alcohol. 

Since in most naturai protOberberines C13 has no substituent, or at most a methyl or methoxyl group (Refs. 2, 17), it is of interest to be able to avoid the arylation of C13 observed in 21. Fortunately, this is achieved by the presence of a methyl group at the corresponding position in the pyrrolinedione, which has enabled us to carry out total synthesis of corydaline (22)- 3,4-dimethoxybenzyne (22d) reacts regioselectively with the pyrrolinedione 29b to give a 32% yield of the adduct 34a. which reduction with lithium aluminium hydride and sodium borohydride converts into corydaline (Scheme 11)(Ref. 16). 

Lai er Rings.—Humulene A -monoepoxide (250) is the major product of WClg-n-butyl-lithium reduction of humulene triepoxide. It is reduced by lithium aluminium hydride or lithium-ethylamine to the 5-alcohol (251 X = OH, Y = H). The isomeric 4-alcohol (251 X = H, Y = OH) can be prepared from humulene-bis-epoxide. All -cis-cyclododeca-l,5,9-triene reacts with chlorosulphonyl isocyanate to give a good yield of mono-adduct, which can be hydrolysed to the p-lactam (252). Reactions of iV-bromosuccinimide in the presence of water, methanol, and acetic acid, with CIS- and trans-cyclododecene have been examined. cis- and trans-l-Nitrocyclo-dodecenes are interconverted on irradiation further irradiation causes isomerization to 3-nitro-trans-cyclododecene. ... 

An ab initio study of the addition of lithium aluminium hydride (LAH) to acetonitrile and malononitrile is reported the free anions generated by hydride addition show clear preferences for the enamide (RCH CH=NH RCH=CHN H) over the imide (RCH2CH=N ). Lithium ion pair formation stabilizes both tautomers, the localized imide is stabilized slightly more than the enamide, and the enamide preference is somewhat reduced but persists. The alane-complexed lithium ion pairs result in a small imide preference for the LAH adduct of acetonitrile and a dramatically reduced enamide preference for the LAH adduct of malononitrile. Alane affinities were determined for the lithium ion pairs formed by LiH addition to the nitriles. The alane binding greatly affects the imide-enamide equilibria such that alane complexation might even provide... 

---