Lithium enolates ring openings

Butyl-lithium induces ring opening of furfuryl selenides to form enolates of allenic ketones (Scheme 33). Isomerization of the allenic ketone to the... 

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

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... 

SCHEME 14. Ring opening of a-hthiated epoxides formation of lithium enolates... 

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). 

Section 1.1.1.3.1.1.2.1.). Similarly, the reductive ring opening of cyclopropyl ketones, e.g., 8, with lithium in ammonia affords specific enolates20,21. These enolates can, of course, be used for selective alkylation. Furthermore, enol acetates, e.g., 10, are regiospecifically obtained by nucleophilic ring opening of cyclopropyl ketones21. 

A highly Z-selective olefination of a-oxy and a-amino ketones via ynolate anions has been reported (Scheme 9).43 The stereocontrol mechanism has been explained by (g) orbital interactions between the s orbital of the breaking C-O bond or n orbital of the enolate and the s orbital of the C-O or C-N bonds of the substituent in the ring opening of the /I-lactone enolate intermediates, and/or the chelation to lithium. 

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... 

Vinyl epoxides can also be ring-opened via an Sn2 sense, as exemplified in the macrocyclization of the epoxy-tethered cyclopentenone 76, which was induced to occur by treatment with lithium 2,2,6,6-tetramethylpiperidide (LTMP) followed by the mild Lewis acid diethylaluminum chloride in THF. The enolate attacked exclusively from the a-position of the... 

Using the lithium enolate of a-bromopropionate, trans and cis /V-(p-toluenesul-finyl)-2-methyl-2-carbomethoxy aziridines 191 were prepared from (S)-47.101-103 The -isomers predominate. Regio- and stereoselective aziridine ring-opening leads to efficient asymmetric syntheses of (-)-a-methylphenylalanine (192),102 (+)-a-methyl-p-phenylserine (193),102 (+)-2-methyl-3-phenylpropanoic acid (194a),103 and (-)-2-methyl-3-aminopentanoic acid (194b).103... 

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... 

Multisubstituted five-membered aromatic heterocycles are synthesized via this cascade protocol (equation 34). The cycloadditions of a-acyloxyketones 78a with lithium ynolates afford /3-lactone lithium enolates 79a, which spontaneously cyclize to give bicyclic compounds 80a. These intermediates, which are stable enough to be isolated, are treated with TsOH under heating to provide substituted furans 81a via decarboxylation and dehydration. Thiophenes (e.g. 81b) are also synthesized by the analogous scheme via intermediate 80b using a-acylthioketones (78b) as a substrate. In the synthesis of pyrroles using a-acylaminoketones as a substrate, the cyclization proceeded at —20 °C, and the -lactone was subsequently ring-opened via /3-elimination to furnish pyrroles in one-pot (equation 35). ... 

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. 

Crotti and co-workers extensively studied the ring-opening functionalization of oxi-ranes using a variety of alkali-metal salts. Several oxiranes were reacted with ammonium halides [119], KCN [120], NaNa [121], lithium acetyhde [122], amines [123], and ketone enolates [124] in the presence of alkali-metal salts to afford the formation of the corresponding 8-functionalized alcohols and some of the results are listed in Table 1. 

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