Lithium Triethylborohydride Research Articles

Tritylketone und Tritylenone. Beiträge zur sterisch erzwungenen Michael‐Addition und zur diastereoselektiven Aldol‐Addition

Tritylketones and Tritylenones. Contributions to the Sterically Enforced Michael Addition and to the Diastereoselective Aldol AdditionTritylketones are prepared from trityllithium and aldehydes, with subsequent CrO3 oxidation (Scheme 1, 2a‐f). Tritylenones are obtained from the saturated ketones and aldehydes or ketones, preferably by (CH3)3Al‐mediated aldol addition with subsequent dehydration (Scheme 2, products 2e, 4b‐e). The carbonyl of the tritylketone group is sterically protected, but electronically effective (see A‐C); thus, amine‐free enolate solutions can be obtained directly with BuLi; also, exclusive conjugate addition of organolithium derivatives occurs with tritylenones (Schemes 3‐5, products 2d, 5‐7, 15 examples). The lithiumenolates of tritylketones add to aldehydes with practically complete stereoselectivity (Scheme 6, products 10, 9 examples): due to the bulkiness of the trityl group, only the (Z)‐enolates 8 are formed, and the approach of the two trigonal centers in the aldol‐addition step is enforced to occur with relative topicity ul. As a first example of an X‐ray structure determination of a silyl enol ether, the crystal structure of (Z)‐2‐(trimethylsilyloxy)‐1, 1, 1‐triphenyl‐2‐butene (9) is reported. Fortunately, the blocking of the carbonyl group in trityl ketones can be run very specifically (without epimerization at the α‐carbonyl center) by lithium triethylborohydride to furnish, after aqueous workup, primary alcohols and Ph3CH (Eqn. 4, products 13–20, 10 examples); the OH‐group of the aldols 10 must be EE‐, MOM‐ or MEM‐protected (Scheme 8) before this C,C‐bond cleavage can be conveyed. Some of the cleavage products are used for the chemical correlation of the aldol configuration and for the demonstration of the synthetic value of the presented method (see 21–29).

Synthesis of 2-deoxy, 3-deoxy, and 2,3-dideoxy analogs of α,α-trehalose by reductive desulfonyloxylation of p-toluenesulfonates with lithium triethylborohydride

Lithium triethylborohydride reacts readily with the 2-tosylate, the 2,2′-ditosylate, the 2,3,2′-tritosylate, and the 2,3,2′,3′-tetratosylate of 4,6;4′,6′-di- O-benzylidene-α,α-trehalose ( 1), to give products resulting both from O-desulfonylation and from reductive C-desulfonyloxylation. Among the products obtained were the known, symmetrically modified, 2,2′- and 3,3′-dideoxytrehalose analogs (as bis-benzylideneacetals) having the α- d- ribo, α- d- ribo and α- d- arabino, α- d- arabino configurations, respectively, as well as three new, crystalline, unsymmetrical analogs, namely, the 2,3′-dideoxy isomer with the α- d- ribo, α- d- arabino configuration, a 2-monodeoxy analog (α- d- ribo, α- d- gluco), and a 3-monodeoxy analog (α- d- arabino, α- d- gluco). The α- d- altro, α- d- gluco isomer of 1 was isolated as a crystalline by-product in one of the reactions.

Formation of lithium cyclopentadienide by the reaction of Li(C 2H 5) 3BH with cyclopentadiene, and a convenient preparation of [M(CO) 3(C 5H 5)] − (M = Cr, Mo and W)

Commercially available lithium triethylborohydride, Li(C 2H 5) 3BH, (1 M, THF) reacts with C 5H 6 in THF solution at room temperature to give a yellow-orange solution of Li(C 5H 5) with gas evolution. Molybdenum hexacarbonyl, Mo(CO) 6, reacts with this solution to give Li[Mo(CO) 3(C 5H 5)] in a high yield after 12 h reflux. Both W(CO) 6 and Cr(CO) 6 give the corresponding cyclopentadienyl carbonyl anions after 15 h reflux in a somewhat lower yield. The corresponding cyclopentadienyl carbonyl dimers, [M(CO) 3(C 5H 5)] 2 have also been prepared and characterized.

The formation of branched-chain deoxypentofuranosides by ring contraction in the reductive desulfonyloxylation of hexopyranoside p-toluenesulfonates

Several methyl 6-deoxy-, 6-deoxy-6-halo-, and 6-O-p-tolylsulfonylhexopyranoside 2- and 4-p-toluenesulfonates reacted readily with lithium triethylborohydride in boiling tetrahydrofuran under reductive desulfonyloxylation at C-2 and C-4, respectively, and with reduction at C-6 where applicable. The desulfonyloxylations proceeded with ring contraction to furnish, in 40–60% isolated yields, new branched-chain pentofuranoside derivatives, namely, methyl 2,5-dideoxy-2-C-(hydroxymethyl)pentofuranosides having the α-L-xylo, α-D-xylo, and α-D-ribo configurations (from 2-tosylates), and methyl 3,5-dideoxy-3-C-(hydroxymethyl)pentofuranosides having the α-D-arabino and α-D-ribo configurations (from 4-tosylates). In some of the reactions, reductively desulfonyloxylated but unrearranged products were formed in addition. Methyl 4,6-O-benzylidene-2,3-di-O-p-tolylsulfonyl-α-D-galactopyranoside reacted by partial de-O-sulfonylation and partial desulfonyloxylation, with and without ring contraction, to give methyl 3,5-O-benzylidene-2-deoxy-2-C-(hydroxymethyl)-α-D-lyxo-pentofuranoside, methyl 4,6-O-benzylidene-3-deoxy-α-D-lyxo-hexopyranoside, and the parent 2,3-diol.

Stereoselective synthesis of (±)-ancistrofuran and its stereoisomers

The four possible stereoisomers of ancistrofuran have been prepared from γ-cyclohomocitral. Addition of 3-furyl-lithium yielded two epimeric alcohols. Each alcohol was epoxidised with m-chloroperbenzoic acid and reduction with lithium aluminium hydride gave mixtures of two diols in each case. Treatment of each mixture with toluene-p-sulphonyl chloride gave the four stereoisomers of ancistrofuran. A stereoselective synthesis was also developed to the trans-fused ancistrofuran which was identical with the natural isomer. Lactol (22) was conveniently prepared by di-isobutyl aluminium hydride reduction of lactone (23). Reaction of the lactol with 2 mol equiv. of 3-furyl-lithium gave a mixture of two diols in 3:1 ratio. Oxidation with manganese dioxide gave ketone (24) which underwent reduction with lithium triethylborohydride in a highly stereoselective manner to yield diol (13). Ketone (24) was also prepared in one step by reaction of lactone (23) with 1 mol equiv. of 3-furyl-lithium. Subsequent treatment of diol (13) with toluene-p-sulphonyl chloride gave ancistrofuran, identical with the natural product. The stereoselective reduction of the γ-hydroxy ketone has been discussed and is suggested to involve ‘chelation control’.

Regiospecific and stereoselective conversion of ribonucleosides to 3′-deoxynucleosides. A high yield three-stage synthesis of cordycepin from adenosine.

Treatment of 2′,3′-anhydroadenosine (obtained 2 in 92% yield from adenosine) with lithium triethylborohydride (or deuteride) gave cordycepin (or its 3′( R )-deuterio derivative) in ≈90% overall yields with no 2′-deoxy isomer detected.

Synthesis of paniculides B and C

A stereoselective approach to the paniculide skeleton is reported utilising an approach based on the dilithioacetate opening of an α-hydroxy epoxide. Two isomeric α-hydroxy epoxides were prepared from 3,5-dimethoxy-1,4-dihydrobenzyl methoxymethyl ether which, in turn, was obtained from 3,4,5-trimethoxybenzoic acid. Reaction of the trans-epoxy alcohol proceeded with high regio- and stereo-control to yield a cis-fused δ-butyrolactone. A similar reaction with the analogous cis-epoxy alcohol gave the trans-lactone in low yield but with excellent regioselectivity. Following oxidation of the hydroxy group in the cis-fused lactone, a double bond was introduced into the cyclohexane ring via a seleniation–oxidative elimination protocol. The regioselectivity in this case was 8: 1 in favour of the required enone. Reduction of this enone with lithium triethylborohydride proceeded in a highly stereoselective manner to give two alcohols in the ratio 98:2, the major (desired) epimer being derived via hydride attack from the least hindered α-face. Finally, epoxidation of the allylic alcohol derivative with m-chloroperbenzoic acid gave two epoxy lactones in a highly stereoselective manner in the ratio 95:5. The derivative in which the δ-butyrolactone, hydroxy, and epoxide groups were all cis could be readily converted into paniculides B and C.

Evidence for single electron transfer in the reduction of organic halides by lithium triethylborohydride

Evidence for single electron transfer in the reduction of organic halides by lithium triethylborohydride

ChemInform Abstract: STEREOSELECTIVE SYNTHESIS OF (.+‐.)‐ANCISTROFURAN: STEREOSELECTIVE REDUCTION OF A Γ‐HYDROXYKETONE

AbstractAusgehend vom Lacton (I) erhält man über (II) ein Gemisch der Furanderivate (IV), das zum Keton (V) oxidiert wird.

Preparation of methyl 3,6-dideoxy-α- d- xylo-hexopyranoside (methyl α-abequoside) and its α- l- lyxo isomer by reduction of epoxides with lithium triethylborohydride

Preparation of methyl 3,6-dideoxy-α- d- xylo-hexopyranoside (methyl α-abequoside) and its α- l- lyxo isomer by reduction of epoxides with lithium triethylborohydride

Hydroboration. 66. Addition of lithium triethylborohydride to substituted styrenes. A simple, convenient procedure for the Markovnikov hydroboration of aromatically conjugated olefins and the synthesis of unusual mixed trialkylboranes

Hydroboration. 66. Addition of lithium triethylborohydride to substituted styrenes. A simple, convenient procedure for the Markovnikov hydroboration of aromatically conjugated olefins and the synthesis of unusual mixed trialkylboranes

Regio et stereochimie de la reduction de derives d'alcools propargyliques catalysee par un complexe de palladium (O)

Regio and stereoselectivity of the palladium catalyzed reduction of propargylic halides and esters is greatly influenced by the nature of the hydride donor as by the leaving group. Best results in allene formation are observed in the reduction by lithium triethyl-borohydride of mesylates and phosphates. In the former case, reaction occurs with anti displacement of the sulfonyl group.

Stereoselective synthesis of (±)-ancistrofuran: stereoselective reduction of a γ-hydroxyketone

A remarkably stereoselective reduction of a γ-hydroxyketone with two equiv. of lithium triethylborohydride has been observed and this effect has been suggested to originate from ‘chelation control’; the reaction has been utilised in a short stereoselective synthesis of ancistrofuran.

Selective reductions. 31. Lithium triethylborohydride as an exceptionally powerful nucleophile. A new and remarkably rapid methodology for the hydrogenolysis of alkyl halides under mild conditions

Selective reductions. 31. Lithium triethylborohydride as an exceptionally powerful nucleophile. A new and remarkably rapid methodology for the hydrogenolysis of alkyl halides under mild conditions

Selective reductions. 32. Structural effects on the reduction of epoxides by lithium triethylborohydride. A kinetic study

Selective reductions. 32. Structural effects on the reduction of epoxides by lithium triethylborohydride. A kinetic study

Reduction of Organofluorine Compounds with Lithium Triethylborohydride.

Reduction of Organofluorine Compounds with Lithium Triethylborohydride.

Desulfonyloxylations of some secondary p-toluenesulfonates of glycosides by lithium triethylborohydride; a high-yielding route to 2- and 3-deoxy sugars

Lithium triethylborohydride (LTBH) reacts readily with p-toluenesulfonates of methyl 4,6- O-benzylidene-α- d-glucopyranoside ( 4) to give deoxyglycosides in > 90% yield. Thus, the 2,3-ditosylate ( 1) and the 3-monotosylate ( 2) thereof afford methyl 4,6- O-benzylidene-2-deoxy-α- d- ribo-hexopyranoside ( 7) in highly regio- and stereo-selective reactions that proceed via methyl 2,3-anhydro-4,6- O-benzylidene-α- d-allopyranoside ( 6), and the 2-monotosylate ( 8) of 4 gives the 3-deoxy-α- d- arabino isomer ( 12) of 7 via the corresponding 2,3-anhydro-α- d-mannopyranoside 11. In the series of the corresponding β anomers, the 3-monotosylate 14 and the 2-monotosylate 16 are similarly desulfonyloxylated, with equal ease, but furnish mixtures of regioisomeric deoxyglycosides, namely, the 3- and 2-deoxy-β- d- ribo derivatives 20 and 21, and 2- and 3-deoxy-β- d- arabino derivatives 22 and 23, respectively. It could be shown that this difference is due to the failure of the intermediary, β-glycosidic epoxides 18 and 19 (the anomers of 6 and 11) to obey the Fürst-Plattner rule in their reductive ring-opening with LTBH. The β-glycosidic 2,3-ditosylate 15 reacts less readily, and gives 20–23, with 20 preponderating. The 2-O-methyl-3- O-tosyl-β- d-glucopyranoside 24 is partly desulfonylated and partly desulfonyloxylated, whereas its 3- O-methyl-2- O-tosyl isomer 27 undergoes desulfonylation exclusively. The reductions of 1, 2, and 8 by LTBH are compared with those previously effected by lithium aluminum hydride, which are slower, involve considerable desulfonylation, and afford lower yields of deoxyglycosides, with the main products differing from those obtained by the action of LTBH. Mechanistic differences associated with the two reductants are discussed.

Reaction of 3‐methoxy‐17‐methylmorphinan‐6‐one with formaldehyde

AbstractReaction of 3‐methoxy‐17‐methylmorphinan‐6‐one (1) and formaldehyde with the presence of calcium hydroxide in aqueous dioxane gave 7,7‐bis(hydroxymethyl)‐3‐methoxy‐17‐methyl‐5‐methylenemorphinan‐6β‐ol (2a). Catalytic reduction of 2a yielded the 5α‐methyl compound, 2b. Tosylation of 2a,b followed by lithium triethylborohydride reduction gave either 7α‐methyl‐6β,7β‐oxetanes 4a,b or 7,7‐dimethyl‐6β‐ols 5a,b, depending on reaction conditions. The C‐6 ketones 6a,b were prepared by oxidation of 5a,b. One compound in this series, 6a, had antinociceptive activity.

An application of the palladium-catalyzed, allylic amination of unsaturated sugars: a new synthesis of d-forosamine

Methyl 4- O-benzoyl-6-bromo-6-deoxy-α- d-glucopyranoside, obtainable from methyl 4,6- O-benzylidene-α- d-glucopyranoside ( 1), was converted into the 2,3-unsaturated 4-benzoate ( 3) by application of the triiodoimidazole method. Debenzoylation of 3, followed by acetylation, afforded crystalline methyl 4- O-acetyl-6-bromo-2,3,6-trideoxy-α- d- erythro-hex-2-enopyranoside ( 5). Treatment of 5 with benzylmethylamine under conditions of palladium-catalyzed, allylic substitution gave a separable mixture of the corresponding 4-( N-benzyl)methylamino-6-bromo-2-enoside (37%) and the 4,6-di-[( N-benzyl)methylamino]-2-enoside (55%). Debromination of 5 with lithium triethylborohydride, proceeding with simultaneous deacetylation, readily yielded methyl 2,3,6-trideoxy-α- d- erythro-hex-2-enopyranoside ( 8). The 4-acetate of 8 (obtained by reacetylation), and also its 4-benzoate (prepared by a different synthetic route), furnished high yields (∼80%) of methyl 4-[( N-benzyl)-methylamino]-2,3,4,6-tetradeoxy-α- d- erythro-hex-2-enopyranoside ( 13) upon palladium-catalyzed animation with benzylmethylamine. Catalytic hydrogenation of 13 effected saturation of the alkenic double bond and removal of the N-benzyl group, to afford methyl 2,3,4,6-tetradeoxy-4-methylamino-α- d- erythro-hexopyranoside, which was subsequently N-methylated with formaldehyde and sodium borohydride, to give its N,N-dimethyl analog, methyl α- d-forosaminide ( 15). The overall yield of 15 from 1 was 24%. Hydrolysis of 15 to the free sugar has been described previously.

Total synthesis of tetracyclic sesquiterpenoids: (±)-ishwarone

A stereoselective total synthesis of the racemic modification of the tetracyclic sesquiterpenoid ishwarone (2) is described. Treatment of the known ketal aldehyde 19 with dibromomethylenetriphenylphosphorane gave the dibromo alkene 20, which was transformed efficiently into the propargylic alcohol 21. The latter compound was converted via the intermediates 22–24 into the octalone 12, which in turn was transformed by standard methodology into the corresponding ketal 7. Treatment of 7 with bromoform–aqueous sodium hydroxide in the presence of a phase-transfer catalyst, followed by acid hydrolysis of the resultant crude product, gave the crystalline keto dibromide 27. When a solution of the corresponding ketal 26 in tetrahydrofuran–hexamethyl-phosphoramide containing methyl iodide was treated with tert-butyllithium, the monobromo ketals 28 (58%) and 29 (38%) were formed. Compound 28 was converted by means of conventional reactions into the keto alcohol 32. Attempts to transform the latter substance into (±)-ishwarone (2) proved unsuccessful. When the olefinic ketal 7 was allowed to react with dimethyl diazomalonate in the presence of copper bronze, the diester 44 was produced in good yield. The latter intermediate was converted via standard methodology into the keto dimesylate 47 which, upon reaction with lithium chloride in ether–hexamethylphosphoramide, gave the corresponding dichloride 48. Treatment of 48 with potassium tert-butoxide in tetrahydrofuran resulted in an intramolecular alkylation to provide the tetracyclic keto chloride 50. Reduction of 50 with lithium triethylborohydride in tetrahydrofuran afforded (±)-ishwarol (51) which, upon oxidation with pyridinium chlorochromate in dichloromethane, furnished (±)-ishwarone (2).