1- lithio-2,3-dimethyl

A related approach directed toward cyclohexane derivatives affords products without carbon substituents on the rings. Ozonolysis of the 6-deoxyhex-5-enopyranoside derivative 14, followed by silylation, gives the unusual pseudolactone 15 in high yield, and this reacts with lithio dimethyl methylphosphonate to yield the cyclohexenone 18 (Scheme 3),... 

An interesting method for the introduction of the isopropylidene moiety has been described, using keten thioacetal chemistry. Thus, the reaction of the enolate of ketone (27) with carbon disulphide followed by methylation gives the keten thioacetal (28). Double conjugative addition and elimination, using lithio-dimethyl cuprate, then affords the isopropylidene ketone (29). Similar method-... 

In order to exploit the reactions of the C-lithio derivatives of iV-unsubstituted pyrroles and indoles, protecting groups such as t-butoxycarbonyl, benzenesulfonyl and dimethyl-amino have been used 81JOC157). This is illustrated by the scheme for preparing C-acylated pyrroles (211) (8UOC3760). 

Indole, 3-hydroxymethyl-2-phenyl-stability, 4, 272 Indole, I-hydroxy-2-phenyl-synthesis, 4, 363 Indole, 2-iodo-synthesis, 4, 216 Indole, 3-iodo-reaetions, 4, 307 synthesis, 4, 216 Indole, 2-iodo-l-methyl-reaetions, 4, 307 Indole, 2-lithio-synthesis, 4, 308 Indole, 3-lithio-synthesis, 4, 308 Indole, 2-mereapto-tautomerism, 4, 38, 199 Indole, 3-mercapto-tautomerism, 4, 38, 199 Indole, 3-methoxy-synthesis, 4, 367 Indole, 5-methoxy-oxidation, 4, 248 Indole, 7-methoxy-2,3-dimethyl-aeetylation, 4, 219 benzoylation, 4, 219 Indole, 5-methoxy-l-methyl-reduetion, 4, 256 Indole, 5-methoxy-l-methyl-3-(2-dimethylaminoethyl)-reaetions... 

Selenophene, 2,5-dimethyl-3-mercapto-synthesis, 4, 956 tautomerism, 4, 946 Selenophene, 2,4-diphenyl-synthesis, 4, 135 Selenophene, 2,5-diphenyl-lithiation, 4, 949 UV spectra, 4, 941 Selenophene, 2-ethoxycarbonyl-mercuration, 4, 946 Selenophene, halo-reactions, 4, 955 Selenophene, 2-hydroxy-Michael reaction, 4, 953 tautomerism, 4, 36, 945, 953 Selenophene, 3-hydroxy-tautomerism, 4, 36, 945 Selenophene, 3-hydroxy-2,5-dimethyl-tautomerism, 4, 945, 953 Selenophene, 2-hydroxy-5-methyl-methylation, 4, 953 tautomerism, 4, 945 Selenophene, 2-hydroxy-5-methylthio-tautomerism, 4, 945 Selenophene, 3-iodo-synthesis, 4, 955 Selenophene, 3-lithio-reactions, 4, 79 synthesis, 4, 955 Selenophene, 2-mercapto-tautomerism, 4, 38 Selenophene, 3-mercapto-tautomerism, 4, 38 Selenophene, 2-mercapto-5-methyl-synthesis, 4, 956 tautomerism, 4, 946 Selenophene, 3-methoxy-lithiation, 4, 949, 955 synthesis, 4, 955 Selenophene, methyl-oxidation, 4, 951 synthesis, 4, 963 Selenophene, 2-methyl-lithiation, 4, 949 Selenophene, 3-methyl-synthesis, 4, 963... 

Thiazole, 4-isopropyl-2,5-dimethyl-quatemization, 6, 254 Thiazole, 2-lithio-... 

Thiophene, 2,5-dimethyl-3-lithio-ring opening, 4, 81 Thiophene, 2,5-dimethylthio-3,4-disubstituted synthesis, 4, 872 Thiophene, dinitro-... 

Knef and coworkers have fouad that 2-lithio-2-sulfoaylpropane and 2-lithio-2-nitropropane behave differenlly in the addition to dimethyl alkylidenemalonate. Thus, 2-Lithio-2-snlfonyl-propane reacts with it iiimost exclusively on the CSii-face and leads to the ruin -addnct, whereas 2-lithio-2-nitropropane reacts under similar reaction conditions, exclusively on the Wfi -face, providing the iy)i-prodnct fEq. 4.134. ... 

The aldol reaction of 2,2-dimethyl-3-pentanone, which is mediated by chiral lithium amide bases, is another route for the formation of nonracemic aldols. Indeed, (lS,2S)-l-hydroxy-2,4,4-trimethyl-l-phenyl-3-pentanone (21) is obtained in 68% ee, if the chiral lithiated amide (/ )-A-isopropyl-n-lithio-2-methoxy-l-phenylethanamine is used in order to chelate the (Z)-lithium cnolate, and which thus promotes the addition to benzaldehyde in an enantioselective manner. No anti-adduct is formed25. 

Esters and amides may be sulfinylated. Addition of a mixture of t-butyl acetate and sulfinate ester 19 to a THF-ether solution of magnesium diisopropylamide led to the formation of (R)-(+)-f-butyl p-toluenesulfinylacetate (49) in 90% yield (equation 14)7. t-Butyl propanoate and butanoate also underwent this sulfinylation to give 50 and 51 in yields of 68 and 45%, respectively83. The diastereomeric ratio was 1 1 for 50 and 3 7 for 51. These esters may also be obtained by alkylation of 49. Similarly, treatment of a-lithio-A, A -dimethylacetamide with sulfinate ester 19 gave (R)-( + )-N, Ar-dimethyl-p-toluene-sulfinylacetamide (52) (equation 15)84. 

The lithio-derivative derived from cyclohexyl phenyl sulfone underwent 1,2-addition to cyclohexenylideneacetaldehyde or cinnamaldehyde to give the corresponding / -hydroxysulfones387. Reactions of 2,2-dimethyl-4-lithio-1,3-oxathiane 3,3-dioxide 308... 

SYNTHESIS OF ORTHO SUBSTITUTED ARYLBORONIC ESTERS BY IN SITU TRAPPING OF UNSTABLE LITHIO INTERMEDIATES 2-(5,5-DIMETHYL-l,3,2-DIOXABORINAN-2-YL)BENZOIC ACID ETHYL ESTER... 

Halogenation of 106 with triphenylphosphine, iodine, and imidazole provided the iodo derivative 109. On treatment with lithium aluminum hydride, 109 was converted into two endocyclic alkenes, 110 and di-O-isopro-pylidenecyclohexanetetrol, in the ratio of 2 1. Oxidation of 110 with dimethyl sulfoxide - oxalyl chloride afforded the enone 111.1,4-Addition of ethyl 2-lithio-l,3-dithiane-2-carboxylate provided compound 112. Reduction of 112 with lithium aluminum hydride, and shortening of the side-chain, gave compound 113, which was converted into 114 by deprotection. ... 

Fig. 2.5. Comparison of energy profile (AG) for pathways to E- and Z-product from the reaction of lithio methyl dimethylphosphonoacetate and acetaldehyde. One molecule of dimethyl ether is coordinated to the lithium ion. Reproduced from J. Org. Chem., 64, 6815 (1999), by permission of the American Chemical Society.

A similar type of transmetalation was also seen with l,2-dimethyl-5-trimethylstannylimidazole, which gave the 5-lithio derivative at -100°C, but rearranged to the 2-lithiomethyl derivative at higher temperatures [83JCS(P1)271]. However, transmetalation does not occur with Grignard reagents and 5-substituted imidazoles can be successfully prepared via this route (Scheme 49) (81 Mil 82OPP409). 

A variety of heterocyclic systems containing unsaturated nitrogen can partake in directed aromatic or heteroaromatic lithiations. Pyrazole (II,D), tetrazole (II,G,2), imidazoline (V,B,2), and pyridine (IV,A,4) derivatives were discussed in the sections indicated. In addition, lithio derivatives of 2-oxazoline 178 (76LA183), 4,4-dimethyl-2-oxazoline 179 (790R1 85T837),... 

Ketones. The lithio derivative of ( +)-(.S )-. Y,.S -dimethyl-S-phenylsulfoxiinine (16), or its enantiomer, may be used both to resolve racemic ketones164 and to determine absolute configurations of ketones. For example, rac-19 on addition of 16 formed the diastereomeric /j-hydroxy-sulfoximines 17 and 18 which were separated. The configuration of 17 was established by an X-ray analysis. The ketones can be regenerated from the /1-hydroxysulfoximines by thermolysis. Thus, heating of 17 and 18 to 80 °C (for 12 h) furnished 19 [a precursor of (+ )-modhephen] and ent-l9165. 

The lithiation of sterically fixed r/,v-4,6-dimethyl-1,3-dithiane gave the equatorial lithio compound 2-lithio-4,6-dimethyl-l,3-dithiane, since only equatorial products are obtained by reaction with electrophiles57. 

For 1,4 addition to enones, the cuprates of the bislactim ethers have been found to be very useful [88AG(E)1194]. These are made by reacting the lithio derivatives with CuBr SMe2 in the presence of dimethyl sulfide. 

As already demonstrated in the previous natural product synthesis, the alkylation of 2,2-dimethyl-l,3-dioxan-5-one SAMP/RAMP hydrazones is a reliable tool with which to synthesize chiral 4-substituted 2,2-dimethyl-l,3-dioxan-5-ones in gram quantities and with high enantiomeric excesses [68]. Thus, after metalla-tion of the RAMP hydrazone (R) -96 the corresponding lithio azaenolate was alkyl-... 

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