Alkylidenemalonate

Reaction of 2-aminopyridine and its 4-methyl derivative and diethyl alkylidenemalonates 356 at 175°C for 1.5-2.5h yielded 3-vinyl derivatives 358, after the isomerization of the exocyclic double bond in 357 (99ACS901). Reaction of 2-amino-4-methylpyridine and bis(2,4,6-trichlor-ophenyl) benzylidenemalonate in the presence of NEt3 afforded only non-cyclised product 359. 2-Aminopyridine and its 4-methyl derivative with diethyl benzylidene- and hexylidenemalonates at 190 °C did not give cyclized products (99ACS901, 99MI29). 

Knef and coworkers have fouad that 2-lithio-2-sulfoaylpropane and 2-lithio-2-nitropropane behave differenlly in the addition to dimethyl alkylidenemalonate. Thus, 2-Lithio-2-snlfonyl-propane reacts with it iiimost exclusively on the CSii-face and leads to the ruin -addnct, whereas 2-lithio-2-nitropropane reacts under similar reaction conditions, exclusively on the Wfi -face, providing the iy)i-prodnct fEq. 4.134. ... 

Alkylidenemalonate esters are also good acceptors in reactions with silyl ketene acetals of thiol esters under very similar conditions.322... 

Various methylenetetrahydrofurans were accessible by a combination of a Zn-promoted Michael addition and a cyclization using alkylidenemalonates and pro-pargyl alcohol as substrates, as reported by Nakamura and coworkers [108]. Tetrasubstituted pyridines of type 2-189 have been obtained through a solvent-free InCl3-promoted domino process of 2-187 and 2-188 (Scheme 2.44) [109]. 

AJC287>. From a complex reaction mixture of BuCH(COCl)2 and 2- 4-[(4-hydroxy-3-carboxyphenyl)hydrazi-no]phenylsulfonylamino pyridine at elevated temperature, tf yr/r >-(3-butyl-2-hydroxy-4-oxo-4//-pyrido[l,2-tf]pyrimi-din-3-ylium)hydroxide was isolated <2001MI53>. Reaction of 2-aminopyridines and diethyl alkylidenemalonates at 175 °C yielded 3-(2,2-disubstituted vinyl)-2-hydroxy-4//-pyrido[l,2-tf]pyrimidin-4-ones from the initially formed... 

DIASTEREOSELECTIVE FORMATION OF TRANS-1,2-DISUBSTITUTED CYCLOHEXANES FROM ALKYLIDENEMALONATES BY AN INTRAMOLECULAR ENE REACTION DIMETHYL (1 R,2 R,5 R)-2-(2 -ISOPROPENYL-5 -METHYLCYCLOHEX-1 -YL)-PROPANE-1,3-DIOATE... 

Generally, the reactions of amines and 2-acylmalonates afforded not only the corresponding 1-(substituted amino)alkylidenemalonates (301), but also carboxamides and diethyl malonate (39JA2890 54JIC711 77GEP2705446). 

The reactions of isopropylidene (l-methylthioalkylidene)malonates and arylamines in boiling ethanol for 2-4 hr, or in diphenyl ether at 140°C for 0.5 hr, afforded isopropylidene l-(aryIamino)alkylidenemalonates (440) in 54-87% yields (87S482). 

The cyclization of isopropylidene l-(phenylamino)alkylidenemalonates (1165) in diphenyl ether at 25Q-260°C under nitrogen, or in boiling Dowtherm A, gave 2-substituted 4-hydroxyquinolines (1166) in 63-96% yields (69BRP1147760 87S482). 

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... 

Iodine may be employed as a mediator to achieve a-hydroxylation of carbonyl compounds. In basic methanolic solution containing iodide, oxidation was reported to lead to a-iodo ketones, which further reacted to give a-hydroxy ketals [171]. The electrolysis of alkylidenemalonates in the presence of iodide as a mediator has been shown to yield cyclopropane derivatives [172]. 

The 1,4-addition of sp3-geminated organodimetal compounds, prepared by the Gaude-mar/Normant coupling reaction, to alkylidenemalonate gives Z-alkene selectively through elimination of the malonate moiety (equation 33)56,57. 

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 addition of Grignard reagents to 1,1-doubly activated alkenes, e.g. alkylidenemalonates (105),68 84a d alkylidenecyanoacetates (106),84e-f alkylideneisocyanatoacetates (107),alkylidenephos-phonoacetates (108),848 isopropylidenemethylenemalonates (109)84iaddition mode exclusively (Schemes 34 and 35). Similarly, as shown in Scheme 36, Mukaiyama reports that the addition of Grignard reagents to chiral oxazepines (110) and (111) affords an enantiose-lective synthesis of -substituted carboxylic acids.85... 

The addition of allylic (or benzylic) zinc halides to alkylidenemalonates (105),lo2s-c alkylidene-cyanoacetates (106),l02d e alkylidenephosphonoacetates (108),84,1 alkylidene barbiturates102f and their ary-lidene analogs occurs exclusively in a 1,4-addition mode. However, the addition of allylic zinc halides to alkylidenemalonates (105) is temperature dependent at low temperatures (-15 C), the homoallylic ma-lonate (128) is obtained, while at higher temperatures (68 C) the isomeric 2-cyclopentenedicarboxylate esters (129) are obtained by a zinc halide promoted electrocyclic closure of the intermediate ester (127 Scheme 48).102 ... 

Kraus has shown that organolithiums add to diethyl alkoxymethylenemalonate in excellent yields to afford diethyl alkylidenemalonates similarly, orf/io-lithiated phenol ethers and ketone enolates afford al-koxy-carbonyl coumarins (306 and 307).217a b In contrast, the treatment of diethyl alkoxymethylenemalo-... 

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... 

Bernadi and Scolastico, and later Evans in a more effective manner, indicated that the enantioselective addition reaction using silyl enol ethers can be catalyzed by Lewis acidic copper(II) cation complexes derived from bisoxazolines [38-40]. In the presence of the copper complex (S,S)-14 (10 mol %), silyl enol ethers derived from thioesters add to alkylidenemalonates or 2-alkenoyloxazo-lidone in high ees (Scheme 12). Bernadi, Scolastico, and Seebach employed a titanium complex derived from TADDOL for the addition of silyl enol ethers to nitroalkenes or 2-cyclopentenone [41-43], although these are stoichiometric reactions. 

Tandem intramolecular 1,3-dipolar cycloadditions and cycloreversion, phosphinimine alkylidenemalonate cyclization, and retro-malonate additions have been reviewed.52 The origins of the stereoselection in the 1,3-dipolar cycloadditions to chiral alkenes53 and the 3 + 2-cycloadditions of fullerene, Cea, have been reviewed.54 The selectivity of the double 3 + 2-cycloaddition of tethered double vinyl carbene species in die presence of C6o varies witii the nature of the tether.55... 

Maruoka and coworkers developed the diastereo- and enantioselective conjugate addition of nitroalkanes to alkylidenemalonates under mild phase-transfer conditions... 

HF calculations with the 6-31G(d) basis set were used to study the mechanism of the Michael addition (or Friedel-Crafts alkylation) reaction of indole with dimethyl alkylidenemalonate. This reaction proceeds through two transition states, TSi and TS2 in the first step, assumed to be rate determining, the new C-C bond is formed, whereas in the second step, proton transfer from indole to malonate occurs with the formation of the new C-H bond. The calculations show that the transfer and interaction of the 7r-electrons in the reactant molecules may play an important role in the cleavage of the original C=C bond and the formation of the new bonds (C-C and C-H) the electron transfer is believed to be the driving force for the reaction to occur. 

Michael-adducts obtained by Barbas et al. (ref. 43) from the addition of acetone to alkylidenemalonates... 

Conjugate addition of RMnCl to alkylidenemalonic esters proceeds in generally good yields (80-87%, equation I), which are generally higher than those obtained by use of RLi or RMgCl. A new synthesis of citronellol (1) is based on this reaction.3... 

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... 

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