Ring opening reactions lithium enolates

Scheme 8.37 Use of the lithium enolate of acetaldehyde DMH in an epoxide ring-opening reaction.

A novel route to a-isocyano-esters involves a ring-opening reaction of 5-alkoxyoxazoles (Scheme 33) isolated yields are ca. 80%. a-Trimethylsilyl esters cannot normally be obtained directly from ester enolates owing to the preference for O- rather than C-silylation. This can be overcome by treating a-chloroacyl silanes with lithium alkoxides (Scheme 34) yields are ca. 80%. 

Oxirane ring opening reaction with a nucleophile mediated by alkali metal salts has been studied extensively. Several oxiranes react with ammonium halide [51], KCN [52], NaNs [53], lithium acetylide [54], amines [55], and ketone enolate [56] in the presence of alkali metal salts providing corresponding -functionalized alcohols. 

More traditional carbon nucleophiles can also be used for an alkylative ring-opening strategy, as exemplified by the titanium tetrachloride promoted reaction of trimethylsilyl enol ethers (82) with ethylene oxide, a protocol which provides aldol products (84) in moderate to good yields <00TL763>. While typical lithium enolates of esters and ketones do not react directly with epoxides, aluminum ester enolates (e.g., 86) can be used quite effectively. This methodology is the subject of a recent review <00T1149>. 

Another carbenoid-typical reaction of a-lithiated epoxides is the 1,2-hydrogen shift, illustrated in Scheme 14. Two mechanistic pathways offer an explanation for the formation of the lithium enolate 94 First, the route via the a-ring opening of the epoxide followed by an 1,2-hydride shift in the carbene 93, and second, the electrocyclic ring opening of an oxiranyl anion 95 to an enolate anion 94. Both mechanisms are in accordance with different experimental... 

The anomolous 4-substituted derivatives are observed only when aldehydes are employed as the electrophiles, but interestingly they are almost exclusively the sole products formed in this case. Their formation is believed to arise via reaction with the lithium enolate form of the ring-opened species, with subsequent enolization and ring closure giving rise to the observed products (Scheme 77)(9IJOC449). 

Tetrasubstituted alkenes (214) were obtained with high Z selectivity (>99 1) by reaction of ynolates (211) with a-oxy- and a-amino-ketones (212 X = OR, NR2) (g) at room temperature. According to experimental and theoretical studies, the high Z selectivity is induced by orbital interactions in the ring opening of the /3-lactone enolate intermediate (213), rather than by the initially presumed chelation of the lithium atom.260... 

The monobromide(s) 146 were treated under strong basic conditions at elevated temperature, slowly generating the y-lactone 147 by ring opening, and consecutive Sn2 reaction in 87% yield (Scheme 14). The isopropyl group was introduced in a four-step sequence. Claisen condensation with methyl formate led to a mixture of the enol and the enol ether, which by treatment with diazomethane, yielded in 80% the enol ether, 148. To introduce the methyl groups, the enol ether was converted into the thioenol ether. 1,4-Addition of dimethyl copper lithium afforded the... 

The y-lactam 110 is prepared by the reaction of the lithium silyl-substituted ynolate 105 with the aziridine 108 activated by a p-toluenesulfonyl group. The initial product is the enolate 109, which can be acidified to yield the a-silyl-y-lactam 110. Intermediate 109 can be trapped by aldehydes to afford the a-alkylidene-y-lactams 111 via a Peterson reaction (equation 45) . These reactions may be considered to be formal [3 + 2] cycloadditions as well as tandem reactions involving nucleophilic ring opening and cyclization. 

The spiroketal side-chain of diosgenin has been converted into 22-ketocholes-terol (488) by straightforward reactions. The known enol ether (485), prepared by a modification of Marker s method, was selectively saponified at C(26) and converted into (486) by lithium aluminium hydride reduction of the C(26)-tosylate. Lithium bromide-hydrogen bromide opening of the enol ether ring... 

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