Metal dienolates alkylation

Enolates may be derived from a,/l-unsaturated ketones 16 by base-catalyzed proton abstraction. Under kinetic control the a -proton is abstracted and a cross-conjugated metal dienolate is formed, whereas under thermodynamic conditions the extended dienolate is the major product3,, l. Successful alkylations of dienolates derived from cyclic a,/l-unsaturated ketones have been performed (see Section 1.1.1.3.1.1.2.1.). The related a,/ -unsaturated ester systems have also been investigated22-24. Open-chain structures 16 pose a rather complicated... 

As shown in Scheme 49, the cyclohexylimine of 10-methyl-l(9)-octalin-2-one has been methylated at C-3 via the kinetically formed cross-conjugated dienamine anion (95) or monomethylated at C-1 via the thermodynamically more stable extended anion (96). Steroidal and simpler enones have also been monoalkylated at the a-position via their corresponding hetero- or homo-annular extended dienamine anions. Likewise, a-alkylations are the rule for liAiated a,3-unsaturated aldimines. The thermodynamically controlled procedure for the synthesis of a-methyl a,3-unsaturated ketones is a vast improvement over conventional methodology using extended metal dienolates where a,a-dimethylation is a severe... 

The Birch reduction has been used by several generations of synthetic organic chemists for the conversion of readily available aromatic compounds to alicyclic synthetic intermediates. Birch reductions are carried out with an alkali metal in liquid NH3 solution usually with a co-solvent such as THF and always with an alcohol or related acid to protonate intermediate radical anions or related species. One of the most important applications of the Birch reduction is the conversion of aryl alkyl ethers to l-alkoxycyclohexa-l,4-dienes. These extremely valuable dienol ethers provide cyclohex-3-en-l-ones by mild acid hydrolysis or cyclohex-2-en-l-ones when stronger acids are used (Scheme 1). 

Stork and Danheiser have developed a highly useful procedure for the synthesis of 4-alkylcyclohex-2-enones, which involves a -alkylations of cross-conjugated lithium dienolates of 3-alkoxycyclohex-2-enones, followed by metal hydride reduction of the carbonyl group and hydrolysis (Scheme 30). Numerous applications of this procedure have been reported.Two different alkyl groups may be introduced at the 6-position of a cyclohex-2-enone derivative without difficulty. While dialkylation is generally not a problem in alkylations of cross-conjugated dienolates of cyclohex-2-enones, it was observed when relatively acidic 3-chlorocyclohex-2-enones were employed. ... 

In Scheme 3, two general mechanistic pathways that may be operative for the Ni-catalyzed coupling of 1,3-enynes with carboxaldehydes are depicted. The first pathway involves a prior oxidative addition of Ni(0) to the reductant M R leading to a metal hydride or a metal alkyl species A. The reactive catalyst A may proceed by sequential insertion into the alkyne bond and the carbonyl bond of the electrophile to the formation of the polysubstituted 2,4-dienol 5 via vinyl nickel 4. 

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