Lithium, dichloromethyl

After the umpolung of an aldehyde group by conversion to a l,3 dithian-2-ide anion (p. 17) it can be combined with a carbonyl group (D. Seebach, 1969, 1979 B.-T. GrO-bel, 1977 B). Analogous reagents are tosylmethyl isocyanide (TosMIC), which can be applied in the nucleophilic formylation of ketones (O.H. Oldenziel, 1974), and dichloromethyl lithium (G. KObrich, 1969 P. Blumbergs, 1972 H. Taguchi, 1973),... 

On treatment of the silylated dichloromethyl alcohols 1585 with butyUithium, lithium trimethylsilanolate, MesSiOLi, 98 is ehminated and the 1,1-dichloroolefins 1586 are formed in 40-82% yields [5, 6]. Likewise, treatment of sulfoxide 1587 at -30 °C with excess LDA results in ehmination of trimethylsilanol 4 to afford nearly... 

Treatment of a-dichloromethyl phenyl sulfoxide with lithium diisopropylamide in THF gave monolithiated derivative 122, which upon further treatment with aldehyde afforded the )S-hydroxy-a-dichlorosulfoxide 123. Thermolysis of 123 gave dichloroketone 124, by extruding benzenesulfenic acid as shown below . Similarly, in the reaction of lithio-a-fluoromethyl phenyl sulfoxide and aldehyde, fluoromethyl ketone 126 was obtained, after thermolysis of the hydroxy intermediate 125. Diethylphosphorylmethyl methyl sulfoxide was shown by Miko/ajczyk and coworkers to be lithiated with n-BuLi to intermediate 127, which upon treatment with carbonyl compounds afforded the corresponding a, -unsaturated sulfoxides 128 in good yields. 

The boronic acid ester B was synthesized by transesterification of the corresponding pinacolester A with (lR,2R)-l,2-dicyclohexyl-l,2-dihydroxyethane. Stereoselective chlorination of B was carried out with (dichloromethyl) lithium and zinc chloride. Reaction of the obtained chloroboronic ester C with lithio 1-decyne followed by oxidation of the intermediate D with alkaline hydrogen peroxide afforded the propargylic alcohol E. Treatment with acid to saponify the tert-butyl ester moiety and to achieve ring closure, produced lactone F. Finally, Lindlar-hydrogenation provided japonilure 70 in an excellent yield and high enantiomeric purity. 

Precedents for these reactions include insertion of a CHC1 group from (dichloromethyl)-lithium into the triarylborane C - B bond6 7, the preparation and reactions of achiral (dichloro-methyl)boronic esterss, and reactions of achiral boronic esters with (dichloromethyl)lithium9,10. 

After reaction of an (S,S )-diol boronic ester 1 with (dichloromethyl)lithium yields a 99 1 ratio of (a/ )-a-chloro boronic ester 2 and its (aS)-diastereomer 3 (Section 1.1.2.1.2.1.), further... 

If the pKa of the corresponding acid R1 - H from the stabilized carbanion is smaller than 35, the migration of R1 fails in (dichloromethyl)borate complexes. Failure to convert pinanediol [(phenylthio)methyl]boronate to an a-chloro boronic ester has been reported15. Reaction of (dichloromethyl)lithium with an acetylenic boronic ester resulted in loss of the acetylenic group to form the (dichloromethyl)boronate, and various attempts to react (dichloromethyl)boronic esters with lithium enolates have failed17. Dissociation of the carbanion is suspected as the cause, but in most cases the products have not been rigorously identified. 

Chiral cyclic boronic esters with (dichloroniethyl)lithium at —100 C form borate complexes4. Borate complexes cart also be formed by generation of (dichloromethyl)lithium from dichloro-methane and lithium diisopropylamide in the presence of a boronic ester at —78 C to — 5 C (Section 1.1.2.1.2.2,)28,19. In situ generation of (dibromomethyl)lilhium is required for preparing a-bromo boronic esters (see Sections 1.1.2.1.1.2. and 1.1.2.1.3.2.). 

S)-Pinanediol boronic esters 2 with (dichloromethyl)lithium produce (aS)-a-chloro boronic esters 3. The first experiments provided diastereomerie ratios in the range 75 25 to 98 2. The best results (>94 6) were obtained with phenyl, ethenyl, or 1-phenylethyl attached to the boron atom39 40. The diastereomerie ratios were estimated from the rotations of esters of derived secondary alcohols. It was subsequently found that zinc chloride catalysis of the rearrangement of the intermediate borate complexes 2 improved the yields, usually to 85-95%, with diastereo-meric ratios often >99 1 when R1 = alkyl, as shown by NMR measurements15,43. 

The synthesis of the amino alcohol (5S,6S)-6-amino-5-decanol begins with reaction of the 1-chloropentylboronic ester (Section 1.1.2.1.3.1.) with sodium azide under phase-transfer conditions to form the a-azido boronic ester, which yields the a-chloro- -azidoalkyl boronic ester (1) [yield 92 % 95 % de] with (dichloromethyl)lithium under the usual conditions. The reaction of 1 with butylmagnesium chloride is unusual in that it requires zinc chloride in order to accomplish the replacement of chlorine by butyl to form /J-azidoalkyl boronic ester 2 without boron-azide /1-elimination. Standard peroxidic deboronation and reduction of the azide complete the synthesis15. 

Phthalaldehyde has been made by the action of potassium hydroxide on o- (dichloromethyl)benzaldehyde,6 by the hydrolysis of a,a,a, a -tetrachlorO -xylene,6 and by the hydrolysis of the a cqe/ja -tetraacetate of o-phthalaldehyde.3 The present method is essentially that of Thiele and Gunther.7-8 Hydrolysis of the tetrabromide may also be carried out by treatment with fuming sulfuric acid followed by water.9 For small-scale preparations of o-phthalaldehyde the reduction of N,N,N, N -tetra-methylphthalamide with lithium aluminum hydride is the method of preference.10... 

Nakajima has shown that a-cyclopropyl acyl silane (23) results from reaction of 1-trimethylsilyl cyclopropyl lithium with dichloromethyl methyl ether at low temperature in THF solution, in a reaction said to involve a carbene intermediate and a 1,2-silicon shift (Scheme 56)147. 

Chiral ketones.3 Asymmetric hydroboration of a prochiral alkene with monoisocampheylborane followed by a second hydroboration of a nonprochiral alkene provides a chiral mixed trialkylborane. This product reacts with acetaldehyde with elimination of a-pinene to give a chiral borinic acid ester in 73-100% ee. Treatment of this intermediate with a,a-dichloromethyl methyl ether (2,120 5, 200-203) and lithium triethylcarboxide followed by oxidation results in an optically active ketone in 60-90% ee. 

Summary l-[2,6-bis(dimethylaminomethyl)phenyl]silenes (2a-d) were prepared by treatment of the (dichloromethyl)oligosilanes R (Me3Si)2Si-CHCl2 la-d (a R = Me b R=tert-Bu c R=Ph d R = Me3Si) with 2,6-bis(dimethylaminomethyl)phenyl-lithium and were characterized by NMR studies and (in part) by X-ray stmctural analyses as well as by their reactions with water to give silanols. Treatment of 2a-d with benzaldehyde produced 2,2-bis(trimethylsilyl)styrene (4) and a silanone polymer as the expected products. For the reaction of 2a and 2c with benzaldehyde, an interesting side reaction was observed leading to the 2-oxa-l-sila-l,2,3,4-tetrahydro-naphthalenes 6a and 6c, respectively. 

Scheme 1. The reaction of the (dichloromethyl)oligosilanes la-d with 2,6-bis(dunethylaminomethyl)phenyl-lithium (molar ratio 1 2) a R = Me, b R = tert-Bu, c R = Ph, d R = SiMej.

Summary Methoxy-bis[tris(trimethylsilyl)silyl]methane (4), the first geminal di(hyper-silyl) compound with a central carbon atom, was prepared by the reaction of tris(tri-methylsilyl)silyl lithium with dichloromethyl methyl ether. The structure of 4, which is characterized by considerable distortions due to the spatial demand of the two (MesS aSi groups, is discussed on the basis of an X-ray crystal structure analysis. 

Reaction of chiral boronates (73) with (dihalomethyl)lithium afforded (IS)-l-haloboronate (74), which was converted into (l/f)-l-azidoboronate (75). Homologation of (75) with (dichloromethyl)lithium to 1-chloro-2-azidoboronate, oxidation to azido acid and catalytic hydrogenation afforded (-)-amino acids in 32-63% overall yields with 92-96% ee (Scheme 31). The procedure has also been applied to the preparation of a chiral v/c-amino alcohol. ... 

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