Michael acceptors alkylidenemalonates

PalladiumfO) also catalyzed the 3-component reaction between unsaturated halides or triflates, propai gyl alcohols and the Michael acceptors alkylidenemalonates, leading to the formation of 3-alkylidenetetrahydrofurans <01JOC175>. Highly enantioselective formation of 2-alkylidenetetrahydrofurans was also realized by palladium-catalyzed ene-type cyclizations of 1,6-enynes <01AG(E)249, 01T5137> and l,2-dien-7-ynes <01JA8416>. 

Nitroalkanes282 288 as well as alkyl sulfones283 288 can serve as useful and general alkyli-dene transfer reagents for highly activated Michael acceptors such as alkylidenemalonic esters (equation 131), Alumina-supported potassium fluoride is an effective reagent for the reaction of nitroalkanes282. The alkylidene transfer from sulfones may be promoted by Ni(acac)2289. 

The same experimental procedure can be used with alkylidenemalonate and other related Michael-acceptors, as well as nitroolefins.26 However, under these reaction conditions only one of the two R groups of R2Zn is transferred to the enone. This problem can be solved by using mixed diorganozincs of the... 

Alkylidenemalonates and malononitriles constitute another class of doubly activated olefins that can be used as highly electrophilic Michael acceptors in this reaction. For example, the Michael addition of aldehydes with these compounds has been reported to proceed with very good yields and enantioselectivities using 0-TMS diphenylprolinol 31a as catalyst (Scheme 2.29). On the other hand, the Michael addition of ketones to alkylidenemalonates has... 

Scheme 2.29 Enantioselective Michael reaction using alkylidenemalonates as Michael acceptors.

Alkylidenemalonates were found to be excellent acceptor molecules (111). Reactions of lithium ylides with dimethyl alkylidenemalonates at —78 °C in THF in the presence of f-BuOH were diastereoselective for all the substituents R except methyl, producing Michael adducts as single diastereomers (Scheme 11.24). The only exception was dimethyl ethylidenemalonate, which produces an 86 14 mixture of diastereomeric adducts, the minor diastereomer being syn-adduct. Since dimethyl alkylidenemalonates bear two geminal methoxycarbonyl moieties, one is cis to the terminal substituent R and the other trans, so of these ester substituents can participate in chelate formation in the transition state. When the terminal substituent R is small, there is a chance for the syn-adduct to be produced, which... 

Michael reactions of chiral lithioenamines of p-oxo esters with dimethyl alkylidenemalonates were studied.173-176 Especially the a-alkyl-substituted compounds (161) and (163), derived from L-valine t-butyl ester, afford, after hydrolysis, the adducts (162) and (164), respectively, diastereoselectively and with high ee (Scheme 57).175 In the presence of TMS-C1, even weaker acceptors like acrylates or MVK were shown to react.176 A somewhat related diastereoselective 1,4-addition, followed by a Pictet-Spen-gler-type cyclization, allows the preparation of compound (165 Scheme 58),177 a central intermediate for the synthesis of several alkaloids.177-178... 

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