Methyllithium reaction with water

Although the reactions with water and methanol yield the expected 1,2-addition products 43 and 44, the addition of methyllithium to the Si=Si bond, which is expected to give the disilane 45 after subsequent hydrolysis, has not yet been observed. Haloalkanes react to furnish compounds 46 (X = Cl, Br). In contrast, those haloalkanes in which halide abstraction is impaired react to form the disilanes I R Si—SiR2X preferentially this is also observed in the reactions of 9 with benzyl chloride and 2-chloro-2-methylpropane70. 

Whereas the reactions of sulfones with nucleophiles via pathways A and B of equation 1 are most frequently observed, the nucleophilic substitution reaction by pathway D has been observed only in the cases where the leaving carbanion can be stabilized, or in the highly strained molecules. Chou and Chang3 has found recently that an organolithium reagent attacks the sulfur atom of the strained four-membered sulfone in 34. When this sulfone is treated with 1 equivalent methyllithium, followed by workup with water or Mel, 38 or 39 are formed in high yield. 

To a stirred reaction mixture consisting of 55.0 gm (0.50 mole) of c/s-cyclo-octene and 41.5 gm (0.125 mole) of carbon tetrabromide cooled to —65°C is added 74.0 ml (0.125 mole) of methyllithium in ether (Foote Mineral Co.) over a 45 min period. After stirring at -65° to -68°C for an additional hr, another 80.5 ml (0.135 mole) of methyllithium is added over a -hour period. The reaction mixture is stirred for another i hr at —68°C, warmed to 0°C, water added, the ether separated, washed with water until neutral, dried over sodium sulfate, and then fractionally distilled to afford 11.3 gm (74%), b.p. 62°-63°C (16 mm), d° 1.5060. 

A fairly stable hexaarylarsenate ion was finally obtained in the form of onium-ate complex 133 when spiroarsonium salt 120-1 was reacted with 2,2 -dilithiobiphenyl in ether. With excess 2,2 -dilithiobiphenyl in tetrahydrofurane the reaction proceeds to the lithium salt of the tris-2,2 -biphenylylenearsenate ion (Li-134) which is also obtained, besides arsoranes 117a, 122a, when 133 is treated with phenyl- or methyllithium. With sodium iodide in acetone onium-ate complex 133 is cleaved into its component salts 120-1 and Na-134. Both alkali metal salts Li,Na-134 are moisture sensitive and react readily with water or alcohols so that the hexacoordinated structure is destroyed and the ring-opened arsorane 135 is produced 30). 

The reaction of naphthosulfone (36, Scheme 11) with the lithium aluminum hydride takes two directions. The first route consists in reduction to naphthothiete (34) with subsequent transformations represented in Scheme 10 (34—>56—>57—>58 59) on quenching dilithium intermediate 57 with water (R = H). The second path involves opening the hetero ring with the nucleophile without reduction (36—>65 67) also analogous to (34 -> -> -> 59) for naphtho[l,8-Z c]thiete proper (cf. Schemes 10 and 11). Methyl naphthyl sulfone (67) thus obtained was also prepared by an independent synthesis by treating naphtho[l,8-Z c]sulfone (36) with methyllithium followed by quenching with water (36 66—>67). 

Reaction with methyllithium. Titanium trichloride is reported to react in glyme at — 50° to 80° with methyllithium in ether to give a dark green solution of unisolated product —presumed to be triethyltitanium — which decomposes above —20° to gas and black needles which react with water to yield methane.1... 

The reaction of methyllithium with the 4-methoxyphenylimine of 1-naphthaldehyde in the presence of a chiral ligand derived from a catechol dialkyl ether as an asymmetric controller (A) afforded the corresponding 1,2-addition product as an optically active amine in 70% ee (ref.93). A solution of methyllithium (R Li) (2.0 mmol) in diethyl ether was added at -tOO C to a solution of the imine (R = 1-Naph 1.0 mmol) and ligand A (2.6 mmol) in toluene and the reaction mixture was then stirred for 1 hour at the same temperarture and finally quenched with water. 

The reaction of methyllithium with the weak acid water (pKg of 15.8) gives methane, as shown, and /i-butyllithium (28) also reacts with water to give butane and the hydroxide ion (as LiOH). The reaction just described between an acid and an organolithium reagent is sometimes called metal-hydrogen... 

To a flask cooled with dry ice-acetone (-30° to -40°C) and containing 22.8 gm (0.10 mole) of l,l-dibromo-2,2-dimethylcyclo-propane and 25 ml of dry ether is added 2.2 gm (0.10 mole) of methyllithium in 80 ml of ether over a hr period. The reaction mixture is stirred for i hr, hydrolyzed with water, the ether separated, washed with water, dried, and distilled to afford 6.2 gm (92%), b.p.40°C, 1.4152. 

The dry tosylhydrazone (20 g, 45.5 mmol) is dissolved in 750 ml of 1,2-dimethoxyethane (freshly distilled from lithium aluminum hydride) in a flame-dried 1 liter round bottom flask fitted with a 240 ml addition funnel, a drierite tube and a magnetic stirrer. A 2.05 M ether solution of methyllithium (130 ml, Alfa Inorganics, Inc.—Caution to avoid the mineral oil impurity the methyllithium solution is decanted from a cold solution which contains a precipitate) is placed in the dropping funnel and added over a 60 min period. The temperature of the reaction mixture increases to ca. 35° during the addition however, no cooling precautions are required. The highly colored reaction mixture is stirred for 7 hr and then poured into 1.5 liters of ice water. The flocculent precipitate is digested for 12 hr at room temperature to speed the filtration. After filtration the filter cake is washed with 500 ml water and dried under vacuum at 50° for several hr. The androsta-5,16-dien-3l5-ol is obtained in ca. 70% yield after recrystallization from methanol mp 138-139°. 

An ethereal solution approximately 2.5 molar in methyllithium is prepared from 17 ml of methyl iodide and 4 g of lithium metal in 200 ml of anhydrous ether. A mixture consisting of 150 ml anhydrous ether, 3 g (10 mmoles) of 3jS-hydroxy-5a-androstane-ll,17-dione and 60 ml (0.15 moles) of the above methyllithium solution are stirred at room temperature for 40 hr. The reaction mixture is diluted with 100 ml of water and the ether is removed by distillation. Filtration of the chilled aqueous phase yields 2.6 g (77%) of 1 la,17a-dimethyl-5a-androstane-3a,l l/ ,17j5-triol mp 149-154°. Recrystallization from acetone-hexane yields pure material mp 164-166° [a] —5° (CHCI3). 

To a stirred solution of 177 mg (0.57 mmol) of (3S,4S)-3- [2(S )-(methoxymethyl)pyrrolidinyl]carbonyl -3-methyl-3-(l-oxocthyl)-4-phenylcyclohex-l-ene in 5 mL of THF at 0°C are added 1.4 mL (2 mmol) of 1.4M methyllithium in diethyl ether. After 3 h at 0 "C the reaction is quenched by the addition of water. Diethyl ether is added and the organic phase is washed with 10% aq hydrochloric acid, water and brine. After drying over MgS04, filtration and concentration in vacuo, the product is subjected to flash chromatography (silica gel, hexane/cthyl acetate, 2 1) giving the ketone as colorless crystals vield 80 mg (65 %) mp 49-52 CC [a]D +21.5 (c = 0.74. CHCf,). 

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