Cyclic 2-alkoxycarbonyl

The Dieckmann, Thorpe and Thorpe-Ziegler reactions all involve intramolecular cyclization of a stabilized anion to form a cyclic ketone. The Dieckmann reaction is the intramolecular equivalent of the Claisen condensation and yields cyclic 2-alkoxycarbonyl ketones as primary products, whereas the primary products of the Thorpe reaction are 2-cyanoenamines (Scheme 13). Sub quent hydrolysis affords cyclic ketones but the primary products, particularly those from the Dieckmann reaction, have a useful synthetic role (see Section 3.6.3.S.1). 

The reversibility of the process means that cyclic 2-alkoxycarbonyl ketones can be cleaved by alkoxide in the retro-Dieckmann reaction, a process of synthetic significance (see Section 3.6.9.1). More recently, nonequilibrium conditions have been employed in the reaction and this may lead to a change in regioselectivity (see Section 3.6.3.3.3). 

A [Cu(R-box)L2](SbF6)2-catalysed[l,6]-transannularGosteli-Claisen rearrangement of cyclic 2-alkoxycarbonyl-substituted allyl vinyl ethers gives medium- and large-sized carbacycles (Scheme 15). °... 

Pyridazinecarbohydrazides are prepared in the normal way from an ester or acid chloride and hydrazine or a substituted hydrazine, generally in good yields. Pyridazines with two ortho alkoxycarbonyl groups give cyclic hydrazides with hydrazine, which are pyridazinopyridazines. 

Other functional groups which have a heteroatom rather than a hydroxyl group capable of directing the hydrogenation include alkoxyl, alkoxycarbonyl, carboxylate, amide, carbamate, and sulfoxide. The alkoxy unit efficiently coordinates to cationic iridium or rhodium complexes, and high diastereoselectivity is induced in the reactions of cyclic substrates (Table 21.3, entries 11-13) [25, 28]. An acetal affords much lower selectivity than the corresponding unsaturated ketone (Table 21.3, entries 14 and 15) [25]. 

Not least for the syntheses of natural products, alkoxycarbonylations with formation of allenic esters, often starting from mesylates or carbonates of type 89, are of great importance [35, 137]. In the case of carbonates, the formation of the products 96 occurs by decarboxylation of 94 to give the intermediates 95 (Scheme 7.14). The mesylates 97 are preferred to the analogous carbonates for the alkoxycarbonylation of optically active propargylic compounds in order to decrease the loss of optical purity in the products 98 [15]. In addition to the simple propargylic compounds of type 89, cyclic carbonates or epoxides such as 99 can also be used [138]. The obtained products 100 contain an additional hydroxy function. 

Ketones can be oxidatively carbonylated at the a-carbon via enol intermediates using PdCl2 as the catalyst and Q1CI2 as oxidant [122], The initially formed carbonylation products correspond to a-chlorination and a-alkoxycarbonylation. Under the reaction conditions, these compounds undergo further transformations involving C - C cleavage eventually leading to a mixture of esters and an alkyl chloride or (in the case of cyclic ketones) to a diester and a chloroester (Schemes 20-21). 

A wide range of olefins can be cyclopropanated with acceptor-substituted carbene complexes. These include acyclic or cyclic alkenes, styrenes [1015], 1,3-dienes [1002], vinyl iodides [1347,1348], arenes [1349], fullerenes [1350], heteroare-nes, enol ethers or esters [1351-1354], ketene acetals, and A-alkoxycarbonyl-[1355,1356] or A-silyl enamines [1357], Electron-rich alkenes are usually cyclopropanated faster than electron-poor alkenes [626,1015],... 

Under oxidation conditions, a C—C double bond can be functionalized by either two alkoxycarbonyl groups or one alkoxycarbonyl group and one heteroatom. As shown in Scheme 4.14, two ester groups are successfully introduced to styrene in an enantioselective manner, producing a phenylsuccinic ester using a Pd/MeO-BIPHEP complex. mcw-Diols are converted into cyclic ethers in an asymmetric manner when catalyzed by Pd/chiral bisoxazoline. Intramolecular aminopallada-tion followed by carbomethoxylation gives an cyclic amino ester in moderate ee when catalyzed by a Pd/bis(isoxazoline) complex. " ... 

Fully unsaturated azocines are n- equivalent heterocyclic analogs of cyclooctatetraene. Paralleling the latter, the few azocines that have been prepared exist in the monocyclic form, but reactions of azabicyclo[4.2.0] isomers are observed. In the 1,2-dihydroazocine series the equilibrium between mono- and bi-cyclic valence isomers can be controlled by alkoxycarbonyl substituents. 

Propynyl alcohols have been converted into (Z)-a-(alkoxycarbonyl)methylene /3-lactones by dialkoxycarbonylation in alcoholic media, under a carbon monoxide-air (3 1) atmosphere, using a PdVKI catalyst (Equation 37) <1997J(P1)147>. The (Z)-stereochemistry of the products was attributed to the syn nature of the carbon monoxide insertion. Substitution at the ct-alkyl position was essential to generate the lactone products in good yields. When the propynyl alcohols were cr-alkyl-unsubstituted, no /3-lactone formation was observed instead, a maleic diester and its cyclic isomer were the predominant products. Where substrates were mono-a-alkyl-substituted, yields of the /3-lactone were low, unless the alkyl group was sufficiently sterically bulky. 

Preparation of /I-Alkoxycarbonyl Cyclic Amines by Palladium(II)-Catalyzed Intramolecular Aminocarbonylation... 

Without conjugation of the olefmic double bond to the alkoxycarbonyl function, high selectivity and high reactivity are attained in some cyclic systems. Even ester function can be replaced with ether. Thus, (S)-BINAP-Ru-catalyzed high-pressure hydrogenation of four- and five-membered cyclic lactones or carbonates having an exocyclic methylene bond gives (R)-/3-methyl-/3-propiolactone in 92% e.e., (R)-y-methyl-y-butyrolactone in 95% e.e. [35], and the carbonate of (R)-3-methyl-2,3-buta-... 

Torii and coworkers developed a convenient method for the introduction of an alkoxycarbonyl group at the a-positions of cycloalkanones. It involves a novel anodic cleavage at one of the external C-C bonds of the cyclopropane in the presence of Fe ions, leading to the formation of cyclic j -keto esters (43) in 39-79% yield (Table 14). The reaction temperature has a profound effect on the yield of 43 since at the higher temperature range the formation of 44 was favored. 

Addition to cyclic iminium salts has been utilized in alkaloid synthesis. A zinc-promoted reductive coupling reaction of iminium salts and alkyl halides has been reported by Shono et al. (Scheme 8). Evidence delineating the mechanistic course (organozinc addition or electron transfer reaction) of the addition has not been established. In contrast to organolithium or Grignard additions, aromatic halogen and alkoxycarbonyl substituents are compatible with this methodology. The intramolecular version of this reaction has been employed for the synthesis of tricyclic amines (53 equation 9). 

Some remarks concerning the scope of the cobalt chelate catalysts 207 seem appropriate. Terminal double bonds in conjugation with vinyl, aryl and alkoxycarbonyl groups are cyclopropanated selectively. No such reaction occurs with alkylsubstituted and cyclic olefins, cyclic and sterically hindered acyclic 1,3-dienes, vinyl ethers, allenes and phenylacetyleneThe cyclopropanation of electron-poor alkenes such as acrylonitrile and ethyl acrylate (optical yield in the presence of 207a f 33%) with ethyl diazoacetate deserve notice, as these components usually... 

Alkylation of sodium 1-(alkoxycarbonyl)methyIphosphonates proceeds equally with acetates in THF from low to room temperature or in DME at reflux. The asymmetric allylic alkylation of the sodium diethyl l-(ethoxycarbonyl)methylphosphonate with 3-acetoxy-l,3-diphenyl-l-propene and cyclic allylic acetates in the presence of a chiral palladium catalyst, prepared from chiral phosphine and palladium acetate, in THF at room temperature proceeds in good yields (44-88%) and high ec s. ... 

In the route to amino phosphonic acids, dialkyl l-(alkoxycarbonyl)methylphosphonates, in the presence of NaH in THF or DME, are alkylated with activated aziridines, 3-aIkoxyazetidinium salts, ° ° and cyclic sulfate derived from (5)-l,2-propanediol ° ... 

Unquestionably, one of the most attractive synthetic methods for the preparation of dialkyl 2-(alkoxycarbonyl)ethylphosphonates involves the conjugate addition of a dialkyl phosphite to the carbon-carbon double bond of a,p-unsaturated carboxylates (Pudovik reaction, Scheme 8.44). In the presence of EtONa, diethyl phosphite reacts vigorously with acrylate in EtOH to give the Michael addition product in 84% yield. The reaction is applied with success to the synthesis of dialkyl 2-(alkoxycarbonyl)ethylphosphonates bearing a large variety of acyclic (symmetric - or disymmetric 30 or cyclic (symmetric or disynunetric ) substituents at phosphorus. 

Because dialkyl 2-oxo-(0-(alkoxycarbonyl)alkylphosphonates are valuable synthetic intermediates that may be either converted to die corresponding amino compounds or treated with a variety of carbonyl compounds in a Homer-Wadsworth-Emmons reaction,procedures that effect their preparation are of special importance. The Michaelis-Arbuzov reaction, which furnishes low yields, does not appear to be an appropriate method for the preparation of dialkyl 2-oxo-(fl-(alkoxycarbonyl)alkylphosphonates. One of the most attractive synthetic methods involves the chemoselective reaction of a-metallated dialkyl alkylphosphonates with acylating reagents such as carboxylic acid chlorides, cyclic anhydrides, or esters. 

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