SYNTHESIS Butyllithium

Metalatlon of 2-alkynyl and 1,2-alkadienyl tetrahydropyranyl ethers furane synthesis. /-Butyllithium metalates the lithium alkoxide 1 to afford the allenyllithium compound a quantitatively. This anion reacts with alkyl halides or CH3OH to afford 2. Another metalation-alkylation protonation sequence proceeds via b to afford 3. Hydrolysis of the latter intermediate affords furanes directly. The overall sequence can be performed in one pot from a propargyl tetrahydropyranyl ether, r-butyl-lithium, and an aldehyde. ... 

Olefins, synthesis -Butyllithium. 1,3-Dibenzyl-2-methyl-l, 3,2-diazaphospholidine. Dimethyl methylphosphonothioate. Diphenylsulfonium isopropylide. N-Methanesulfinyl-p-toluidine. Methylphosphoric acid bis(dimethylamide). Phosphoryl chloride-Stannous chloride-Pyridine. p- Toluenesulfonylhydrazine. Triphenyl phosphite. 

The synthesis of pyrazolines and pyrazoles of the [CCNN + C] type with the creation of two bonds, N(2)-C(3) + C(3)-C(4) (or N(l)-C(5) + C(5)-C(4)), has been studied by several groups. Beam and coworkers have published a series of papers on the synthetic utility of lithiated hydrazones. Thus, the methylhydrazone of acetophenone (598) is converted by butyllithium into the dianion (599), which in turn reacts with methyl benzoate to afford the pyrazole (600) (76SC5). In earlier publications Beam et al. have used aldehydes and acyl chlorides to obtain pyrazolines and pyrazoles by the same method. 

A versatile oxirane synthesis via (64) is the sulfur ylide approach (B-75MI50504, cf. 76TL457), which in effect inserts a CR2 group into a carbonyl group (Scheme 71). Older, less generally useful versions of this insertion utilize diazomethane or dibromomethane-butyllithium. 

Pyran, 4-arylimino- C NMR, 3, 585 Pyran, 4-arylimino-2,6-dimethyl-synthesis, 3, 762 Pyran, 2-aryloxytetrahydro-X-ray studies, 3, 621 Pyran, 4-benzyl-isomerization, 3, 666 Pyran, 3-bromodihydro-synthesis, 3, 769 Pyran, -bromodihydro-halogen-metal exchange with t-butyllithium, 1, 474 Pyran, 2-bromotetrahydro- H NMR, 3, 579... 

Thiophene, bromotetrahydromethyl-pyrolysis, 3, 902 Thiophene, 5-t-butyl-2-methyl-dealkylation, 4, 800 Thiophene, chloro-polymerization, 4, 758 reaction with n-butyllithium, 4, 831 synthesis, 4, 835, 882, 933 Thiophene, 2-chloromercurio-reactions... 

Kyba and eoworkers prepared the similar, but not identical compound, 26, using quite a different approach. In this synthesis, pentaphenylcyclopentaphosphine (22) is converted into benzotriphosphole (23) by reduction with potassium metal in THF, followed by treatment with o "t/20-dichlorobenzene. Lithium aluminum hydride reduction of 23 affords l,2-i>/s(phenylphosphino)benzene, 24. The secondary phosphine may be deprotonated with n-butyllithium and alkylated with 3-chlorobromopropane. The twoarmed bis-phosphine (25) which results may be treated with the dianion of 24 at high dilution to yield macrocycle 26. The overall yield of 26 is about 4%. The synthetic approach is illustrated in Eq. (6.16), below. 

Tlie interest in the preparation and use of dithiolium salts in connection with the synthesis of TTF derivatives led to the development of a new uses of heteroaromatic cations in organic synthesis. Based on that, a new carbonyl olefination for the synthesis of numerous heterofulvalenes was developed (77S861). For example, 2-dimethoxyphosphinyl-l,3-benzodithiole was deprotonated with butyllithium in THF at -78°C and the resulting phosphonate carbanion reacted with 9-alkyl-acridones to give the dithia-azafulvalenes of type 45 (78BCJ2674) (Scheme 15). 

In an altogether different type of approach, the hydrazone is formed in situ as a lithium salt. Wilson et al. (80JHC389) described this approach in the one-pot synthesis of 5-aryl-2-phenylpyrazol-3-ones 72a-f from the corresponding hydrazones 65a-f (Scheme 20). The latter were obtained by condensing ketones 64a-f with phenylhydrazine. Treatment of hydrazones 65a-f with n-butyllithium in dry THF, followed by the addition of half a molar equivalent of diethyl carbonate 67 and then quenching the reaction mixture with hydrochloric acid, produced pyrazol-3-ones 72a-f, along with products 71. The yields of the products 72 are in the range 22-97%. Four intermediates—66a-f, 68a-f, 69a-f, and 70a-f— were proposed for this reaction. 

In a modified procedure the free carboxylic acid is treated with a mixture of mercuric oxide and bromine in carbon tetrachloride the otherwise necessary purification of the silver salt is thereby avoided. This procedure has been used in the first synthesis of [1.1.1 ]propellane 10. Bicyclo[l.l.l]pentane-l,3-dicarboxylic acid 8 has been converted to the dibromide 9 by the modified Hunsdiecker reaction. Treatment of 9 with t-butyllithium then resulted in a debromination and formation of the central carbon-carbon bond thus generating the propellane 10." ... 

The synthesis of phosphonium iodide 24, the precursor of phos-Br phorus ylide 12, begins with the alkylation of 5-lithio-2-methyl- furan,10 derived from the action of n-butyllithium on 2-methylfuran 17 (16), with 1,4-dibromobutane (17) to give 15 in 75% yield (see... 

In total synthesis, model studies are frequently performed on simpler systems prior to the final assault on the target molecule. In the synthesis of zaragozic acid A (1), 2-methyl-1,3-dithiane (92) was employed as a simple model for the more elaborate dithiane 67. Deprotonation of 92 with n-butyllithium under standard conditions47 and addition of the aldehyde provides a mixture of two diastereoisomers, 93 and 94 (Scheme 22), in approximately equal amounts. One of the diastereoisomers (93) lacks the TMS group,... 

Using oxathiane 11, ( + )-(i )-2-methoxy-2-phenylpropanoic acid was obtained in 97% ee, however, the synthesis contains some inconvenient reaction steps. Thus, reduction of ( + )-10-camphorsulfonic acid (8) leads in low yield to a mixture of 10-mercaptoisoborneol (9 A) and 10-mercaptoborneol (9B) which must be separated by chromatography. The oxathiane 10 resists deprotonation with butyllithium and, therefore,, y -butyllithium had to be employed. Furthermore, after addition of methylmagnesium iodide, cleavage of the oxathiane moiety 12, with iodomethane did not proceed as well as with the simpler oxathianes 3. 

The synthesis of enantiomerically pure propargylic alcohols is possible using the same methodology 43b. Thus, addition of (—)-[(l-chloro-2-phenylethyl)sulfinyl]-4-methylbenzene (14) to propan-al led to a mixture of the diastereomers 15A/15B (d.r. 44 56) which are easily separated by column chromatography. After thermal elimination of the sulfinyl group the vinyl chlorides 16A/16B were obtained as a mixture of E- and Z-oleftns. Elimination of hydrogen chloride was carried out with three equivalents of butyllithium, leading to enantiomerically pure 1 -phenyl-1-pentyn-3-ol. 

In ( )-[2-(l-propenyl)-l, 3-dithian-2-yl]lithium, no problem of EjZ selectivity arises. It is easily prepared by deprotonation of the allylic dithiane87,88 with butyllithium in THF, whereas deprotonation of the 2-propylidene-l, 3-dithiane requires the assistance of HMPA. The addition to saturated aldehydes proceeds with excellent y-regioseleetivity and anti selectivity88,89. As often observed in similar cases, aldehydes which bear an, p2-carbon atom adjacent to the carbonyl group give lower selectivities. The stereoselectivity decreases with ketones (2-bu-tanone y/a 84 16, antiisyn 77 23)88. The reaction with ethyl 2-oxopropanoate is merely nonstereoselective90, but addition of zinc chloride improved the syn/anti ratio to 96 4, leading to an efficient synthesis of ( )-crobarbatic acid. 

Reaction of a-sulphinyl carboxylic esters 421 with carbonyl compounds has usually been performed using a Grignard reagent as a base. No condensation products are obtained using t-butyllithium or sodium hydride367,496,497 (equation 251). The condensation products formed are convenient starting materials for the synthesis of a, p-unsaturated esters and /1-ketones497. 

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