3- Alkoxy-2-cyclohexenones

The starting materials for annulative cyclization are cycloalkenones that contain the allylsilane side chain in the 4-position. Such starting materials can easily be prepared from vinylogous esters40. Furthermore, reactions of 3-alkoxy-2-cyclohexenones with functionalized iodides in the presence of lithium diisopropylamide provides an excellent route to such precursors41 34 35. 

Stork-Danheiser alkylation (5, 403-404). An example of this useful kinetic alkylation of 3-alkoxy-2-cyclohexenones to give 6-alkyl derivatives has been submitted to Organic Synthesis.9... 

The Stork-Oanheiser alkylation of 3-alkoxy-2-cyclohexenones under conditions of kinetic enolate formation at the 6-position has enjoyed extensive application in alicyclic synthesis. Such kinetic enolates have... 

Scheme 2.24 Cu-catalysed 1,4-addition of ZnEt2 to cyclohexenone with alkoxy-7V-heterocyclic carbene ligand.

The structure of the products is determined by the site of protonation of the radical anion intermediate formed after the first electron transfer step. In general, ERG substituents favor protonation at the ortho position, whereas EWGs favor protonation at the para position.215 Addition of a second electron gives a pentadienyl anion, which is protonated at the center carbon. As a result, 2,5-dihydro products are formed with alkyl or alkoxy substituents and 1,4-products are formed from EWG substituents. The preference for protonation of the central carbon of the pentadienyl anion is believed to be the result of the greater 1,2 and 4,5 bond order and a higher concentration of negative charge at C(3).216 The reduction of methoxybenzenes is of importance in the synthesis of cyclohexenones via hydrolysis of the intermediate enol ethers. 

Scheme 6.4. Diastereoselectivity in conjugate addition of organocopper reagents to alkoxy-substituted cyclohexenones 20 and 21 (Bn = benzyl, TBS = t-butyidimethylsilyl).

Cyclohexenone is reduced either by sodium amalgam [138] or electrochemically in acetonitrile containing tetrabutylammonium fluoroborate [139] and affords mainly the tail-to-tail diketonic hydrodimer. Some 10-26% of the head-to-tail hydrodimer has been detected in the mixture of products from reduction at a mercury cathode in aqueous ethanol under both acidic and basic conditions [140]. Substituents on the 3- and 4-positions, as in XXXIII, cause formation of some head-to-tail XXXV and head-to-head hydrodimers XXXVI (see Table 9). The product ratios depended on the concentration of water in acetonitrile used as solvent. Other work discussed later indicates that the presence of metal ions that can coordinate with alkoxy groups also changes these product ratios. 

Among the more reactive and synthetically useful dienes are doubly and triply activated alkoxy- and amino-substituted dienes, such as ( )-l-methoxy-3-(trimethylsilyloxy)-1,3-butadiene (Danishefsky s diene),( )-l-(dimethylamino)-3-(fert-butyldimethylsilyloxy)-1,3-butadiene (Rawal s diene)-, and 1,3-dimethoxy-l-(trimethylsilyloxy)-1,3-butadiene (Brassard s diene). As illustrated below, the cyclo-addition products arising from these dienes can either be hydrolyzed or treated with fluoride ion to remove the silyl group, which is followed by (3-elimination to provide conjugated cyclohexenones. 

Another difference in the reactivity of these two ylids is reflected in their reactions with a, 3-unsaturated ketones. The carboethoxy dimethylsulfonium methylid 620 reacted with cyclohexenone to give the usual alkoxy sulfonium salt 621. Intramolecular displacement of dimethyl sulfide led to the expected oxirane (622) analogous to the formation of 614. Dialkylsulfonium ylids react via 1,2-addition with displacement of the... 

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