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The reduction of the 1‐phospha‐2‐azanorbornene derivate endo‐1 with lithium aluminium hydride leads to an unprecedented 1‐phosphabicyclo[3.2.1]octa‐2,5‐diene, while a phospholide anion is formed with lithium. The latter can be protonated resulting in formation of an unusual 2H‐phosphole dimer. Furthermore, 3H‐phospholes, previously assumed to have no synthetic relevance as intermediates, were proposed to act as dienophile in the dimerisation of 3,4‐dimethyl‐1‐phenylphosphole at elevated temperatures based on theoretical calculations., 1‐Phospha‐2‐azanorbornenes (PAN) are shown to be suitable starting materials for novel bridged 7‐membered phosphorus heterocycles (using lithium aluminium hydride as reducing agent) or lithium phospholide (with elemental lithium as reducing agent). Artwork by Dr. Christoph Selg.

In this paper, we investigated the LiAlH4-reduction of 5-acetyl-1,6-dimethyl- 4-phenyl-3,4-dihydropyrimidin-2(1H)-one (N-methylated Biginelli compound). Following the reduction and SiO2-promoted dehydration, (Z)-5-ethylidene-1-methyl-6- methylene-4-phenyltetrahydropyrimidin-2(1H)-one was isolated as the major product (33% yield). Chromatographic separation of the reaction products also allowed us to isolate (yield in parentheses) and fully spectrally characterize: 1,6-dimethyl-4-phenyl- 5-vinyl-3,4-dihydropyrimidin-2(1H)-one (20%), 5-ethyl-1,6-dimethyl-4-phenyl-3,4- dihydro-pyrimidin-2(1H)-one (9%), 5-(1-hydroxyethyl)-1,6-dimethyl-4-phenyl-3,4- dihydropyrimidin-2(1H)-one (5%). A possible mechanism explaining the formation of these products is proposed.

Highly functionalized fluorenones were synthesized by an intramolecular cyclization of 2''-halo-[1,1':3',1''-terphenyl]-4'-carbonitriles in the presence of n-butyllithium or lithium aluminium hydride. The precursor was synthesized by ring transformation of 2-oxo-6-aryl/heteroaryl-4-(sec.amino)-2H-pyran-3-carbonitriles or 2-oxobenzo[h]chromenes with o-bromo/chloro/fluoro-acetophenone under basic conditions in moderate yield. We performed the control experiment to understand the proposed mechanism and found that the presence of a secondary amine in the starting material directs the reactivity. The photophysical properties of 3-methoxy-7-(piperidin-1-yl)-5H-indeno[2,1-b]phenanthren-8(6H)-one was explored and solvent dependent emission was observed. These compounds were also tested against HIV-1 and low to moderate activity was observed.

Lithium aluminium hydride reduction of bis-unsymmetric-diaryloxamides 3 is difficult to accomplish especially for the sterically hindered mesityl derivative. Using microwaves LAH reduction of 3a,d was successful in a short time, however, with cleavage of the ether linkage to give compounds 11a,d. Extension of this method enabled the reduction of bis-oxamide derivatives 13 to the corresponding tetraamine derivative 14 which was then converted to the bis-imidazolidinium salt 15. Application of this method led to rapid reduction of unsymmetric N,N'-diaryloxamides 16 to the corresponding N,N'-diarylethylenediamines 17 which were converted to their corresponding imidazolidinium salts 18.

Finding novel pathways for the reduction of carbon oxides is important for the ongoing search for new systematic entries to hydrocarbon feedstocks. The CO to formyl conversion with readily available hydrides represents an important step along this way. Using boranes as the reducing reagents is desirable and potentially useful. Reactions of trialkylboranes with carbon monoxide are synthetically established. H. C. Brown had shown that R3B systems readily react with CO at 100 to 125 8C at normal pressure to yield the respective tertiary alcohols after oxidative workup. They modified this procedure to achieve the synthesis of ketones and aldehydes. In the latter case lithium aluminium hydride reagents were added. However, carbon monoxide is surprisingly reluctant to be reduced with [B]H boranes. Carbon monoxide is reported to react with B2H6 at 100 8C and 20 atm to give “borane carbonyl” [H3B-CO], a gas (b.p. 64 8C) that dissociates at atmospheric pressure. We have now found that B H borane reduction of carbon monoxide can be carried out with a suitable borane at a frustrated phosphane/borane Lewis pair (FLP) template. We stirred a mixture of the bulky cyclopentenylphosphane 1 with the hydroboration reagent [HB(C6F5)2] [9] for about 15 minutes at RT and then subjected the resulting mixture to an atmosphere of carbon monoxide (2 bar). Workup after 12 h at RT eventually gave the reduction product 2 as a colorless solid in 63% yield (see Scheme 1). Single crystals of 2 were obtained from dichloromethane/n-pentane. In the crystal compound 2 contains a “h-formyl” B(C6F5)2 subunit that is bonded through the acyl carbon atom (C1) to the phosphorus atom and through the acyl oxygen atom (O1) to the boron center (B1) of the FLP framework (see Figure 1 and Table 1). The resulting six-membered heterocycle fea

The efficient formation of a bicyclic oxazolidine by lithium aluminium hydride reduction of a tertiary amide provides an example of intramolecular nucleophilic capture of an iminium ion equivalent by the oxygen of a silyl ether.

Ethyl 5-chloroimidazole-4-carboxylate has been prepared by diazotisation of ethyl 5-amino-1-(di-O-isopropylidene-α- or -α,β-D- mannofuranosyl)imidazole-4-carboxylate, reaction of the diazonium salt with copper(I) chloride and removal of the 1-substituent with hydrochloric acid, or by similar conversion of ethyl 5-amino-1-t-butylimidazole-4-carboxylate to ethyl 1-t-butyl-5-chloroimidazole 4-carboxylate, and removal of the t-butyl group with hydrogen bromide. Ethyl 5-fluoroimidazole-4-carboxylate has been prepared from ethyl 5-amino-1-t-butylimidazole-4-carboxylate by diazotisation and photolysis in the presence of tetrafluoroboric acid. Ethyl 5-chloroimidazole-4- carboxylate and ethyl 5-fluoroimidazole-4-carboxylate have been converted into the corresponding alcohols by reaction with lithium aluminium hydride. 5-Chloro-4-(hydroxymethyl)imidazole has also been prepared by electrolysis of 5-chloroimidazole-4-carboxylic acid at a mercury cathode. 5-Chloroimidazole has been converted into the 5-chloroimidazolyl analogues of metiamide and cimetidine by a sequence of reactions, and 5-fluoroimidazole has been similarly converted into the 5-fluoro-analogue of metiamide. The metiamide and cimetidine analogues were found to be histamine H 2-receptor antagonists.

Treatment of 3,4-benzoxanthone hydrazone with tetrahalogeno-α-benzoquinones gave the corresponding cyclic ethers (IIIa-b). Reductive cleavage of the latter with lithium aluminium hydride yielded 3,4-benzoxanthene together with the tetrahalogenocatechol. Whereas active hydrogen compounds effect cleavage of the dioxole ring in IIIa-b with the formation of the corresponding benzo-xanthylene, they react with 9-hydroxy-3,4-benzoxanthene yielding the benzoxanthyl derivatives (VIII). Diazoalkanes on 3,4-benzoxanthione afford the corresponding ethylene sulfides. The thermochromic properties of the ethylenes, obtained by the action of copper on the ethylene sulfides, are stressed. Reaction mechanisms are discussed.

The rearranged product resulting from the action of lithium aluminium hydride upon holarrhenine tosylate (IV) in ether solution has been tentatively formulated by Uffer as C-nor-D-homoconessine (V). We found that holarrhenine mesylate (III) is converted into the same rearranged product on reacting with sodium borohydride in refluxing alcohol. The spectroscopic analysis of the rearranged product confirms the proposal of Uffer and gives results which completely parallel those obtained by Lukacs et al. in their study on the product of the reaction of the sulfonic esters of 12β-hydroxyconanine1 with aluminium dichlorohydride. Further converging data are afforded by a reaction sequence involving consecutive Hofmann degradations of the rearranged product (V).

In a model study directed towards the synthesis of 5,10-diazasteroids, piperidazine was condensed with 2-methoxycarbonylmethylcyclohexanone (2) to give decahydro-Δ7a(11a)-6-oxopyridazo[1,2-a]cinnoline (4). Reduction of 4 with lithium aluminium hydride yielded decahydro-Δ7a(11a)-pyridazo[1,2-a]cinnoline (5). Subsequent reduction of 5, either catalytically or with sodium borohydride, proceeded stereospecifically to the perhydropyridazo[1,2-a]cinnoline (8), with B/C cis ring fusion.

The lithium aluminium hydride reduction of N-2-(1,1-dichloroalkylidene)-anilines 3 afforded mainly the rearranged secondary amines 4 next to the normally expected secondary amines 5. The formation of the rearranged secondary amines 4 is explained by an aziridine intermediate. The highly branched derivative 3d gave the aziridine 6d in good yield, besides the secondary amine 5d.

Experimental evidence is provided that the rearrangement of N-aryl α,α-dichloroketimines with lithium aluminium hydride in ether, observed as a competitive reaction during the stereospecific synthesis of cis-aziridines, proceeds via consecutive transformation of α-chloroaziridines into azirinium chlorides and α-imidoylcarbenium ions, the latter being trapped by chloride anion to afford β-chloroenamines, which furnish rearranged anilines on treatment with lithium aluminium hydride.

Treatment of N-1-(2-chloro-2-methylpropylidene) amines with potassium cyanate in methanol afforded 1-substituted-4-methoxy-5,5-dimethyl-2-imidazolidinones, which were easily converted into the non-methoxylated derivatives, i.e. 1-substituted-5,5-dimethyl-2-imidazolidinones, by reaction with lithium aluminium hydride in diethyl ether. The structure was confirmed by independent synthesis of the latter heterocycles and their isomeric structure (4,4-dimethyl derivative). The formation of the 2-imidazolidinones, starting from α-chloroaldimines and potassium cyanate, involved a rearrangement of the imino-nitrogen atom, which was explained by an aziridine intermediate.

A general synthetic route to N-1-(2,2-dichloroalkylidene) amides is described, starting from aliphatic 2,2-dichloroaldehydes and an appropriate N-unsubstituted amide. The adducts thus formed were converted into N-(1,2,2-trichloroalkyl) amides with thionylchloride and subsequently dehydrohalogenated with triethylamine. These N-acyl α,α-dichloroaldimines were found to be very apt to nucleophilic addition at the activated carbon-nitrogen double bond, producing stable adducts. The configuration of the adducts in solution was determined by NMR-spectroscopy. Treatment of the title compounds with lithium aluminium hydride in diethylether afforded 1,2-dialkylaziridines. The reactivity of these N-acyl α,α-dichloroaldimines was compared with the reactivity of the N-alkyl analogues and the corresponding oxygen analogues, i.e. α,α-dihalogenated aldehydes.

A non-catalytic reduction of α-oximinoketones 1 and α-oximinoalcohols 2 to erythro-2-amino-1-arylalkan-1-ols 3 with lithium aluminium hydride is reported. The erythro-2-amino-1-arylalkan-1-ols are isolated as their hydrochlorides 5 and characterised as the erythro isomers by benzoylation.

3-(Trichlorogermyl)propanoic acid (1a) reacts with phenylmagnesium bromide in molar ratio 1:4 to give 3-(triphenylgermyl)propanoic acid (2a). In the compounds 1a and 2a the β-carboxylic functional group shows some unusual properties when they react with excess of phenylmagnesium bromide. The compound 1a reacts with phenylmagnesium bromide in molar ratio 1:5 to give phenyl 2-(triphenylgermyl)ethylketone (3a) and in molar ratio 1:6 to give 1,1-diphenyl-3–(triphenylgermyl)propanol (4a). The compound 2a reacts with phenylmagnesium bromide in molar ratio 1:2 to give 3a and in molar ratio 1:3 to give 4a also. Dehydration of the compound 4a with dilute hydrochloric acid seems especially easy. Moreover, the compound la reacted with phenylmagnesium bromide in molar ratio 1:6, then the mixture was treated with dilute hydrochloric acid to give 1,1-diphenyl-3 (triphenylgermyl)-1-propene (5a) in one pot reaction. Alkyl Ge–C bond in the compound 5a can be cleaved selectively by lithium aluminium hydride (LiAlH4) in good yield.

The title compound 3,4-benzocycloocten-1,5-diyne (1) is a highly reactive hydrocarbon that has been shown to undergo addition reactions with tetraphenyl-cyclopentadienone (tetracyclone) to the 2:1 adduct 6, with octacarbonyldicobalt to the bis metal complex 7, with lithium aluminium hydride to the bis diene 9, and with various electrophilic reagents. In these latter cases cationic intermediates are generated from 1 and a transannular cyclization takes place leading to novel derivatives of 1,2-dihydropentalene (31, 32, 35, 36, 43, 44).

An improved synthesis of [1.1]ferrocenophane-1,12-dione (2) by oxidation of [1.1]ferrocenophane with 2,3-dichloro-5,6-dicyano-p-benzoquinone (DDQ) is presented. The syn conformer of dione 2 is structurally characterized. The compound undergoes various addition reactions at the bridging carbonyl groups. Attempts to add 1,1'-dilithioferrocene result, however, in the diadduct 9, not in the symmetric trinuclear diol 8. Reaction of 2 with sodium cyclopentadienide in the presence of aluminium trichloride (AlCl 3 ) gives the respective difulvene 11 in excellent yield. The dynamic behavior of 11 is investigated by variable temperature 1 H NMR measurements (VT-NMR). The cyclovoltammogram of 11 indicates two reversible oxidation steps. Reduction of difulvene 11 with lithium aluminium hydride (LiAlH 4 ) results in the formation of [1.1]ferrocenophane 12 with cyclopentadienyl anion substituents at either one of the two bridges. While attempts to generate a third ferrocene moiety by reaction with iron(II) choride (FeCl 2 ) have failed so far, the formation of 12 is established by protonolysis and methylation reactions.

Condensation of 2-methyl-1-pyrroline with chloroacetone or 3-chloro-2-butanone using LDA in THF afforded novel 2-(3-hydroxy-2-methyl-1-alkenyl)-1-pyrrolines via a peculiar reaction mechanism instead of the anticipated 2-(3-oxobutyl)-1-pyrrolines. The intermediacy of 2-(2,3-epoxy-2-methylalkyl)-1-pyrrolines in the latter transformation was demonstrated by immediate reductive epoxide ring opening utilizing lithium aluminium hydride in diethyl ether. Furthermore, 2-(3-oxobutyl)-1-pyrroline was prepared via an alternative approach through alkylation of 2-methyl-1-pyrroline with 3-chloro-2-(methoxymethyloxy)-1-propene using LDA in THF, followed by acid hydrolysis. Reduction of 2-(3-oxobutyl)-1-pyrroline by sodium borohydride in methanol afforded the corresponding 2-(3-hydroxybutyl)-1-pyrroline in good yield.

A variety of different N-(2,2,3-trichloropropylidene)amines, N-(2,2,3-trichlorobutylidene)amines, and N-(2,2,5-trichloropentylidene)amines were synthesized for the first time, and their reactivity with regard to hydride reagents was investigated. In this way, N-(2,2,5-trichloropentylidene)amines were evaluated as substrates for the synthesis of piperidines, and N-(2,2,3-trichloropropylidene)amines and N-(2,2,3-trichlorobutylidene)amines were reduced efficiently into the corresponding novel beta,beta,gamma-trichloroamines by means of sodium cyanoborohydride in methanol in the presence of acetic acid. Furthermore, N-(2,2,3-trichloropropylidene)amines were transformed into 2-(chloromethyl)aziridines by lithium aluminium hydride in Et2O, and N-(2,2,5-trichloropentylidene)acetamide was used for the First time as a suitable Substrate for the addition of oxygen, nitrogen, and Sulfur nucleophiles in good yields.

Selective reduction of the amide moiety of acyclic and macrocyclic amidoketals was studied in presence of various reagents (BH3 · Me2S, iBuAlH2, Red‐Al®, LiAlH4). The best results were obtained with lithium aluminium hydride in the presence of triethylamine traces, whereas borane dimethyl sulfide gave rise to a partial ketal reduction of the acyclic compound and Red‐Al® to a cleavage of the macrocyclic molecule accompanied by an unexpected trans‐acetalization.

4-Amino-5-methylaminopyrimidine has been synthesized by reduction with lithium aluminium hydride of the formyl group in 4-amino-5-formamido-2-methylthiopyrimidine followed by removal of the 2-substituent. A route to 5-amino-4-hydroxy-6-methylaminopyrimidine is described. The Whitehead synthesis has been extended to the use of cyanoacetic acid as a reactant. Decarboxylation of the resulting 4-amino-5-carboxy-3-methyl-2-pyrimidone, however, gave unexpectedly 2-hydroxy-4-methylaminopyrimidine. Several improvements in the preparation of known related (methylated) compounds, including the first isolation of 5-amino-1-methyl-4-methylamino-2-pyrimidone are described.

Lithium aluminium hydride reduction of bis-unsymmetric-diaryloxamides 3 is difficult to accomplish especially for the sterically hindered mesityl derivative. Using microwaves LAH reduction of 3a,d was successful in a short time, however, with cleavage of the ether linkage to give compounds 11a,d. Extension of this method enabled the reduction of bis-oxamide derivatives 13 to the corresponding tetraamine derivative 14 which was then converted to the bis-imidazolidinium salt 15. Application of this method led to rapid reduction of unsymmetric N,N'-diaryloxamides 16 to the corresponding N,N'-diarylethylenediamines 17 which were converted to their corresponding imidazolidinium salts 18.

Two efficient methods have been developed for the synthesis of variously substituted 2-aminomethylazetidine derivatives 5 by regioselective nucleophilic substitution of 4-mesyloxymethylazetidin-2-ones 3 followed by reduction or by reduction of the appropriate 4-oxo-azetidine-2-carboxamides 7. A novel ring transformation of 4-oxoazetidine-2-carboxamides 7 into tetrahydroquinolines 16 by reaction with lithium aluminium hydride/aluminium trichloride has been investigated.

The reduction of [11C]carbon dioxide to [11C]methanol with lithium aluminium hydride (LiAlH4) and subsequent conversion into [11C]methyl iodide is a standard way of producing the latter precursor for radiolabelling. However, it suffers from appreciable losses by incomplete reduction giving [11C]formate. We show that samarium diiodide (SmI2) can be used to improve the yield of [11C]methanol by its ability to efficiently reduce [11C]formate to [11C]methanol. This can be done either by making [11C]formate intentionally and treating it with SmI2 or by treating the LiAlH4-reduced [11C]CO2 with SmI2. In the latter approach, sodium thiosulphate has a similar effect as SmI2. Hydriodic acid was also shown to exert some reducing action on [11C]formate too. [11C]Carbonate is reduced to a small extent by SmI2 under the mild conditions employed. In contrast to the very easy [11C]formate reduction, SmI2 had little effect on [11C]acetate and practically no [11C]ethanol could be produced. Copyright © 2006 John Wiley & Sons, Ltd.

Model studies show that displacement of fluorine, rather than chlorine, occurs upon reaction of 3,5-dichloro-2,4,6-trifluoropyridine with sodium methoxide and phenoxide. Subsequent hydro-dechlorination can be achieved by reaction with lithium aluminium hydride whereas reaction of sodium in iso-propanol leads to formation of the tri-iso-propoxy pyridine derivative, via nucleophilic substitution of the methoxy group, rather than the dechlorinated products. Macrocycles can be synthesised by reactions of appropriate difunctional oxygen nucleophiles with 3,5-dichloro-2,4,6-trifluoropyridine, one of which was characterised by X-ray crystallography.

2-Organylseleno(telluro)ethyl phosphines and 4-organylthio(seleno (telluro))butyl phosphines were prepared by reduction of diethyl 2-organylseleno(telluro)ethyl phosphonates and diethyl 4-organylthio(seleno(telluro)) butyl phosphonates with lithium aluminium hydride in diethyl ether. 1H and 31P NMR spectra as well as mass spectra of the resulting phosphines were considered. Their stability in regard to the oxidation by oxygen was discussed.

The asymmetric synthesis of protected 2-amino-1,3-diols (S,R)-5 starting from 2,2-dimethyl-1,3-dioxan-5-one is described. The stereogenic centres are generated by α-alkylation using the SAMP/RAMP hydrazone methodology and diastereoselective reduction of the ketones (S)-2 with L-selectride. The resulting alcohols (S,S)-3 are converted into the amines (S,R)-4 by nucleophilic substitution with sodium azide and subsequent reduction with lithium aluminium hydride. The products are obtained in high diastereomeric and enantiomeric excesses (de ⩾ 96%, ee = 90−94%). By employing this methodology, the ammonium salt of D-erythro-sphinganine (R,S)-11 was synthesised starting from RAMP-hydrazone (R)-1 in 47% overall yield and with excellent diastereomeric and enantiomeric excess (de, ee ⩾ 96%). (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)

A complete series of 2,3,4-trideoxy-2,3-epimino and 2,3,4-trideoxy-3,4-epimino derivatives of 1,6-anhydro-β-D-hexopyranoses were prepared by lithium aluminium hydride reduction of vicinal trans azido tosylates. Unusual formation of the aziridine ring from precursors with the trans-diequatorial arrangement of the reacting groups was observed. NMR and infrared spectra of the aziridines are discussed.

β-Hydroxy ketones were synthesized in one-pot from β-diketones by reducing alkyl ketones chemoselectively by keeping aryl ketone intact. Initially, β-diketones were enolized using LiHMDS and later alkyl ketone was chemoselectively reduced efficiently by lithium aluminium hydride. This method produces β- hydroxyl ketones from the corresponding β-diketones in high yield.

Sulfonamides are routinely employed as nitrogen protecting groups in organic synthesis. They are often crystalline, chemically robust, and, most importantly, the basicity/nucleophilicity of the nitrogen atom is reduced dramatically due to the presence of the electron-withdrawing sulfonyl moiety. Unlike their carbamate or amide analogues, there are no spectroscopic problems associated with rotamers when employing sulfonamides as protecting group.

A number of stereoisomeric N-[aryl(alkyl, cycloalkyl)carbonyl]-exo(endo)-5-aminomethylbicyclo[2.2.1]hept-2-enes have been synthesized from bicyclo[2.2.1]hept-2-en-exo(endo)-5-carbonitrile via reduction of the latter by lithium aluminum hydride and subsequent reactions of the resulting amines with aryl(alkyl, cycloalkyl)carbonyl chlorides and anhydrides. The direction of reaction of amides with peroxy acids does not depend on orientation of substituents in the bicyclic fragment: that is, for both exo- and endo-isomers the epoxidations are completed by the formation of N-[aryl(alkyl, cycloalkyl)carbonyl]-exo(endo)-5-aminomethyl-exo-2,3-epoxybicyclo[2.2.1] heptanes. The reduction of stereoisomeric epoxides by lithium aluminium hydride proceeds in different directions; that is, isomers with an exo-oriented amido group form the substituted exo-5-alkylaminomethyl-exo-2,3-epoxybicyclo[2.2.1]heptanes and the reactions of epoxides of endo-amides are accompanied by intramolecular cyclization and completed by the formation of N-[aryl(alkyl, cycloalkyl)]-exo-2-hydroxy-4-azatricyclo[4.2.1.03,7]nonanes. The structures and stereochemical homogenity of the products have been confirmed by the analysis of 1H and 13C NMR spectra, correlation spectroscopy, and nuclear Overhauser enhancement spectroscopy experiments. We discuss the behavior of epoxides and provide an analysis of the coefficients of the atomic orbitals in the molecular orbital–linear combination of atomic orbitals equation (AM1 method). © 2001 John Wiley & Sons, Inc. Heteroatom Chem 12:119–130, 2001

Two syntheses of (±)-[2.2]paracyclophane-4-thiol have been accomplished in two and five steps, with overall yields of 46 and 31%, respectively, from [2.2]paracyclophane. The strategy involves two key reactions: (a) a lithium aluminium hydride reduction of the disulphide of [2.2]paracyclophane and (b) the use of a Newman–Kwart reaction for the conversion of [2.2]paracyclophane-4-ol to [2.2]paracyclophane-4-thiol.

A series of water soluble ferrocenylamine–glucose conjugates, [N-2-(β-D-glucopyranosyloxy)ethyl-, [N-3-(β-D-glucopyranosyloxy)propyl-, [N-5-(β-D-glucopyranosyloxy)pentyl-N-methylaminomethyl]ferrocene, has been synthesized from the methiodide salt of N,N-dimethylaminomethylferrocene and N-(3,4,6-tri-O-benzyl-β-D-glucopyranosyloxy-ethyl, -propyl and -pentyl)amine respectively. N-Methylation of the products from the latter reaction was achieved by formylation followed by reduction with lithium aluminium hydride. Catalytic hydrogenolysis over palladium removed the benzyl protecting groups from the carbohydrate moiety to give the target conjugates. An alternative synthesis of [N-2-(β-D-glucopyranosyloxyethyl)aminomethyl]ferrocene using boron trifluoride–diethyl ether promoted glycosylation of penta-O-acetyl-D-glucopyranose and [N-(2-hydroxyethyl)-N-methylaminomethyl]ferrocene followed by deacetylation of the carbohydrate protecting group using basic ion exchange resin was also developed. The pKa values of the water soluble conjugates were determined.

The synthesis of disaccharides containing sulfur in the reducing ring through a nonglycosylating chemical strategy is described. Lactose, maltose and cellobiose were transformed in sev- eral steps into the appropriately protect- ed 4-O-glycosyl-2,3-O-isopropyliden-al- dehydo-d-glucose dimethyl acetals (6, 11, 18 and 27) and 4-O-glycosyl-2,3-O- isopropyliden-aldehydo-l-idose dimeth- yl acetals (42 a and 42 b). Compounds 6, 11, 18 and 27 were converted into the corresponding 4-O-glycosyl-5,6-dideoxy- 5,6-epithio-2,3-O-isopropylidene-alde- hydo-l-idose dimethyl acetals 33 e - h via the 5,6-cyclic sulfates 31 a - d ,b y reaction with potassium thioacetate or potassium thiocyanate and treatment with NaOMe/MeOH. Nucleophilic ring open- ing of the episulfide ring of 33 e - h, with sodium acetate followed by acidic hy- drolysis, Zemplen de-O-acetylation and acetylation gave the thio disaccharides 4-O-(2',3',4',6'-tetra-O-acetyl-b-d-galac- topyranosyl-, -a-d-glucopyranosyl- and -b-d-glucopyranosyl)-1,2,3,6-tetra-O-ac- etyl-5-thio-a,b-l-idopyranoses (38 - 40). 1,2,3-Tri-O-acetyl-4-O-(2',3',4',6'-tetra-O- acetyl-b-d-galactopyranosyl)-6-deoxy-5- thio-a,b-l-idopyranose (37) was ob- tained by treatment of 4-O-(2',6'-di-O- acetyl-3',4'-O-isopropylidene-b-d-galac- topyranosyl)-2,3-O-isopropylidene-6-S- cyano-5-O-sulfonate-6-thio-aldehydo-d- glucose dimethyl acetal potassium salt (32 a) with lithium aluminium hydride followed by acidic hydrolysis and acety- lation. The analogous thio maltose and cellobiose (47 c and 47 d) were synthes- ised following a similar strategy (5,6- cyclic sulfate!episulfide!thiosugar) from compounds 42 a and 42 b.

Anti-1,2-phosphinyl alcohols 11 and their corresponding syn-isomers upon treatment with phosphorus trichloride and triethylamine give E and Z alkenes respectively, by an anti elimination. This is in marked contrast to the syn Horner-Wittig elimination of the corresponding 1,2-phosphinoyl alcohols. The 1,2-phosphinyl alcohols 11 were prepared by the reduction of 1,2-phosphinoyl alcohols with cerium(III) chloride/lithium aluminium hydride. The anti elimination is explained by the formation of a transient epi-phosphonium species. An unexpected E-selective Horner-Wittig elimination during the cerium(III) chloride/lithium aluminium hydride reduction of a 1,2-phosphinoyl alcohol in which the diphenylphosphinoyl group is adjacent to an aryl group is described. This led to the synthesis of the antimitotic agent E-combretastatin A-4. An alternative synthesis of the 1,2-phosphinyl alcohols from the corresponding phosphine-borane complex is also described.

Asymmetric reduction of prochiral ketones to optically active chiral secondary alcohols was achieved using a reagent prepared by modifying lithium aluminium hydride with a chiral auxiliary, (+)threo-1,16-dibenzyloxy,7,8-dihydroxy hexadecane and various additive alcohols. (+)threo-1,16-dibenzyloxy,7(R),8(R)-dihydroxy hexadecane was prepared from (+)threo-9(R),10(R),16-trihydroxy hexadecanoic acid. Alcohols such as CH3(CH2)n-OH of different chain length (n = 0–11) and (R)-hydnocarpic alcohol were used. Complex prepared from (+)threo-1,16-dibenzyloxy,7(R),8(R)-dihydroxy hexadecane, LAH and (R)-hydnocarpic alcohol reduced acetophenone in moderate enantioselectivity (maximum of 70% ee). Various arylalkylketones were reduced with the same complex.

Lithium aluminium hydride reduction of methyl [7- 14 C]benzoate gave [7- 14 C]benzyl alcohol which was transformed (HBr, H 2 SO 4 ) to [7- 14 C]benzyl bromide. The latter was reacted with lithium N-(bis-methylthiomethylenimino)-acetyl-(2R)-bornane-10,2-sultam (Oppolzer chiral synthon) followed by hydrochloric acid then lithium hydroxide hydrolysis and chromatography on a Dowex 50 column to give (D)-phenyl[3- 14 C]]alanine with 40% overall yield. The molar activity was higher than 50 mCi/mmol and e.e. > 99% as measured by the Marfey method and a modified Marfey method with TLC scanning. The latter method is suitable for the measurement of the optical purity of any amino acid.

The octakis(trimethylsiloxy)calix[4]resorcinarenes, 3 and 4, were synthesized by reaction of 1 and its tetrabromo derivative 2 with hexamethyldisilazane, and were found to exhibit dynamic behaviour in solution. Temperature-dependent NMR investigations confirmed the presence of at least two conformational isomers of 3 in solution. The conformation of 3 in the solid state was determined by an X-ray crystal structure analysis; the calixarene displays a boat conformation. The introduction of the ethoxy group as a spacer into the molecule of 1 was effected via its reaction with ethyl bromoacetate and subsequent reduction with lithium aluminium hydride forming the ethoxy-tethered C-methylcalix[4]resorcinarene 6 in an impure state. Reaction of crude 6 with hexamethyldisilazane furnished the ethoxy-tethered octakis( trimethylsiloxy)calix[4]resorcinarene 7; its hydrolysis led to pure 6.

A (+)-10-Camphorsulfonic acid-catalysed acetal exchange reaction of phenyl 1-thio-β-laminaribioside using 3.5 molar equivalents of α,α-dimethoxytoluene gave a tris(benzylidene acetal), which was isolated and characterized as phenyl 3′-O-acetyl-2,2′ : 4,6 : 4′,6′-tri-O-benzylidene-1-thio-β-laminaribioside, and the corresponding 3′-O-benzyl derivative 6. Upon a treatment with pyridinium p-toluenesulfonate, the interglycosidic 2,2′-acetal in 6 underwent selective cleavage to give the 2,2′-diol. Additionally, a reductive ring-opening reaction of 6 with lithium aluminium hydride/anhydrous aluminium chloride, followed by O-acetylation, gave the 2,6,6′-O-acetyl-4,2′,3′,4′-tetra-O-benzyl derivative in 73% yield. A different regioselectivity was observed in the reduction of 6 with borane-trimethylamine adduct/anhydrous aluminium chloride or sodium cyanotrihydroborate/methanesulfonic acid, giving the corresponding 2,4,4′-triol as the major product.

Phenyldimethylsilyllithium reacts with acyloin silyl ethers RCH(OSiMe3)COR 8 to give regiodefined silyl enol ethers RCHC(OSiMe2Ph)R 9, and hence by hydrolysis ketones RCH2COR 10. The yields can be high but are usually moderate. The mechanism of this reduction is established to involve a Brook rearrangement (Scheme 6) rather than a Peterson elimination (Scheme 1). Although the mechanism appears to be the same in each case, the stereochemistries of the silyl enol ethers 9 are opposite in sense in the aromatic series (R = Ph, Scheme 7) and the aliphatic series (R = cyclohexyl, Scheme 8), with the major aromatic silyl enol ether being the thermodynamically less stable isomer E-PhCHC(OSiMe2Ph)Ph E-9aa, and the major aliphatic silyl enol ether being the thermodynamically more stable isomer Z-c-C6H11CH C(OSiMe2Ph)-c-C6H11Z-9ba. This is a consequence of anomalous anti-Felkin attack in the aromatic series. The reaction with the silyl ether ButCH(OSiMe3)COPh 13b is normal in giving Z-ButCH C(OSiMe2Ph)Ph Z-38 (Scheme 11), but reduction of the silyl ether 8a with lithium aluminium hydride is also anti-Felkin giving with high selectivity the meso diol PhCH(OH)CH(OH)Ph 39. The reaction between phenyldimethylsilyllithium and the acyloin silyl ether 8d (R = But) does not give the ketone ButCH2COBut, but gives instead the anti-Felkin meso diol ButCHOHCHOHBut 40 also with high selectivity (Scheme 12). Silyllithium and some related reagents react with trifluoromethyl ketones 46 and 48 to give α,α-difluoro silyl enol ethers 47 and 49 (Scheme 14).

Racemic dimethyl 4-methoxy- (11 and 12), diallyl 4-allyloxy- (13 and 14) and dimethyl 4-(ethylsulfanyl)-2-hydroxycyclopentane-1,1-dicarboxylates (15 and 16) were prepared by base-catalyzed addition of methanol, allyl alcohol and ethylsulfane, respectively, to dimethyl (4-oxobut-2-en-1-yl)malonate (6). Deallylation of 13 and 14 afforded 4-hydroxycyclopentanes 27 and 28. Reduction of 11-16 with lithium aluminium hydride gave the corresponding 4-substituted 2,2-bis(hydroxymethyl)cyclopentanols. Dimethyl (2S,3S,4R)-, (2R,3S,4R)-3-benzyloxy-4-formyloxy-2-hydroxycyclopentane-1,1-dicarboxylates (35, 36) and dimethyl (2S,3S,4R)-, (2R,3S,4R)-3-benzyloxy-2-benzoyloxy-4-methoxycyclopentane-1,1-dicarboxylates (39, 40) were synthesized starting from D-glucose. Reduction of dimethyl cyclopentane-1,1-dicarboxylates 39 and 40 with lithium aluminium hydride, benzoylation of the formed hydroxy derivatives, hydrogenolysis of benzyl groups, conversion of the liberated hydroxy groups into dithiocarbonates and their reduction with tributylstannane afforded, after removal of the protecting groups, (2R,4R)-1,1-bis(hydroxymethyl)-4-methoxycyclopentan-2-ol ((2R,4R)-17) and (3R,4R)-1,1-bis(hydroxymethyl)-4-methoxycyclopentan-3-ol (51). Reduction of a mixture of esters 35 and 36 gave (2R,3R)-2-benzyloxy-5-(hydroxymethyl)hexane-1,3,6-triol (52) as the major product and (2R,3S,4R)-3-benzyloxy-1,1-bis(hydroxymethyl)cyclopentane-2,4-diol (53) as the minor product. The latter was converted into (3R,4R)-1,1-bis(hydroxymethyl)cyclopentane-3,4-diol (58). 3-Deoxycarba analogues 51 and 58 arose by migration of benzoyl group in the preparation of the dithiocarbonates.

17 alpha-Aminomethyl, 17 alpha-acetamidomethyl, and 17 alpha-hemiglutaramidomethyl derivatives of dihydrotestosterone and testosterone have been prepared by hydrocyanation of 3,3'-(ethylenedioxy)-5 alpha-androstan-17-one and 3,3'-ethylenedioxyandrost-5-en-17-one, reduction of the corresponding acetylated 17 alpha-cyanohydrins with lithium aluminium hydride, and acylation of the resulting 17 alpha-aminomethyl derivatives with either acetic anhydride or the mono acid chloride of glutaric acid mono methyl ester. Saponification of the 17 alpha-hemiglutaramidomethyl methyl esters gave the corresponding hemiglutaramido derivatives, while acid hydrolysis of the 3-ethylene ketal group of 17 alpha-acetamidomethyl and 17 alpha-hemiglutaramidomethyl derivatives regenerated the 3-oxo and 3-oxo-4-ene functions. The 17 alpha-configuration of 17-substituted steroids was determined by 1H and 13C NMR and confirmed by comparing with NMR data for 17 alpha- and 17 beta-cyano-17-hydroxyandrost-4-en-3-one, 17 beta-cyano-3,3'-(ethylenedioxy)androst-5-en-17-ol, 17 alpha-alkynyl, and 17 alpha-hexanoic derivatives of dihydrotestosterone and testosterone, of known 17-configurations. Several ambiguous assignments of 13C NMR signals of 17 alpha-substituted steroids and unsubstituted 17 beta-hydroxy or 17-oxo precursors have been resolved using steroid analogs deuterated at positions C5-7, or C16 for androstane derivatives, and at positions C6-7, or C7 for androstene derivatives. 17 alpha-Aminomethyl and 17 alpha-alkylamidomethyl derivatives of dihydrotestosterone and testosterone are useful intermediates for the access to potential ligands of androgen-binding proteins necessary for affinity chromatography purification or affinity-labeling experiments.

The reaction of pentafluorobenzyl magnesium bromide with phosphorus trichloride in a 2:1 molar ratio led to the disubstituted product, bis(pentafluorobenzyl) bromophosphine 1 , which, upon reaction with lithium aluminium hydride, was converted to bis(pentafluorobenzyl) phosphine 3 . The reaction of 3 with oxygen led to bis (pentafluorobenzyl) phosphine oxide 4 . The reaction of 1,3 and 4 with di- μ -chloro-bis-[( η 6 -mesitylene) chloro-ruthenium (II)] 5 yielded the η 6 -mesitylene-phosphinedichloro-rutheniun (II) complexes 6–8 . Single-crystal X-ray structure determinations are described for the phosphinous acid-ruthenium(II) complex 8 and for the by-product 1,2 bis (pentafluorophenyl)ethane 2 , formed during the Grignard reaction of magnesium and pentafluorobenzylbromide. In 8 , the Ru-C bond lengths can be categorised as four short (219–222 pm) and two long (224–228 pm). A weak intramolecular P-OH···Cl contact (O···Cl, 304 pm) is observed.

The title compounds 7 were prepared in situ by deprotection of the corresponding pivaloyl-substituted oxetanes 3 with lithium aluminium hydride in tetrahydrofuran. under these conditions a reductive ring opening at c-2 (hydrodealkoxylation) occurred which was initiated by a nucleophilic hydride attack and which yielded the triols 8 (64–85%). the facility of the reaction and its high regioselectivity can be explained by the directing ability of the hydroxy group at the aromatic substituent. The reaction proceeds stereospecifically, as shown by deuterium labelling experiments. The prerequisite 2-(2-pivaloyloxyphenyl)-3-[(trimethylsilyl)oxy]oxetanes 3 were prepared by the Paterno-Buchi reaction of the protected salicylaldehyde 1 and various silyl enol ethers 2. The 2-hydroxyphenyl substituent at the C-3 position of oxetane 6 directed the hydride attack to the C-4 position and yielded the triol 10 in 85% yield.

Lithium aluminium hydride reduction of artemisinin produces two unexpected rearrangement products in addition to those reported previously. The structure of the major rearrangement product, a tertiary hydroperoxide, was determined by 2D-NMR and chemical reactions. A mechanism is proposed for this rearrangement, based on the observation that dihydroartemisinin can also be converted into the same hydroperoxide in alkaline solution.

(R)-(2,3,4,5,6-Pentadeuterophenyl)oxirane, 5 was synthesised with an overall yield of 6.3% from benzene-d 6 . Friedel-Crafts acylation of benzene-d 6 with methyl oxalylchloride gave methyl 2-oxo-2-(2,3,4,5,6-pentadeuterophenyl)acetate, I that was chirally reduced (Saccharomyces cerevisiae) to methyl (R)-2-hydroxy-2-(2,3,4,5,6-pentadeuterophenyl)acetate (methyl (R)-d,-mandelic acid), 2. Reduction of 2 with lithium aluminium hydride gave (R)-(2,3,4,5,6-pentadeuterophenyl)ethane-1,2-diol, 3. Tosylation of 3 and subsequent treatment with potassium hydroxide assisted cyclisation to 5.

Lithocholic (1a), chenodeoxycholic (1b), deoxycholic (1c) and cholic acid (1d) were used for the synthesis of the title compouds. Reactions of O-acetyllithocholic acid chloride with piperidine, morpholine and 1-methylpiperazine gave the corresponding amides 2a-2c which were reduced with lithium aluminium hydride to 24-(piperidin-1-yl)-5β-cholan-3α-ol (3a) and analogues 3b and 3c. Heating of the acids 1a-1d with ethylenediamine monotosylate afforded 23-(4,5-dihydroimidazol-2-yl)-24-nor-5β-cholan-3α-ol (4a) and analogues 4b-4d. Compound 4a was similarly obtained from 3α-acetoxy-24-nor-5β-cholane-23-carbonitrile. Identity of the products was corroborated by spectral characterization. Some of the products (in the form of salts) were tested for cancerostatic and antimicrobial activities in vitro with partially promising results.

Reactions of 2-alkynyl arylethynyl selenide 1 with alkyl iodides 3 in the presence of lithium aluminium hydride via allenyl selenoketene 2 afforded cyclobutene 4. Allenyl group of the intermediate allenyl selenoketene 2 was monitored by React IR.

A convenient method for the synthesis of 10-methyl- 8,10-diazabicyclo[4.3.1]decane, possessing a novel diazabicyclic ring system, as an important synthetic organic chemistry building block was developed using octanedioic acid as a starting material. The key transformation in the 5-step synthesis sequence involved a reaction of dimethyl 2,7-dibromooctanoate with methylamine, which resulted in the formation of cis -dimethyl 1-methylazepan-2,7-dicarboxylate. The lat ter was further transformed into bicyclic 8-benzyl-10-m ethyl-8,10-diazabicyclo[4.3.1]decane-7,9dione under heating with benzylamine. Reduction of the formed bicyclic dione with lithium aluminium hydride resulted in 8-benzyl-10-methyl-8,10-diazabicyclo[4.3.1]decane, and hydrogenolysis efficiently yielded the target produ ct.