Stereoselectivity, malonic acid

We also studied the pyridoxal-dependent decarboxylation of an aminomalonic acid, a process providing an a-amino acid as the product. Our interest was to induce stereoselectivity in the process. Therefore, we synthesized catalysts 42 and 43, which rigidly held chirally mounted groups [42]. With the basic 42 we obtained 42% ee favoring l-phenylalanine in the decarboxylation of 2-amino-2-benzyl-malonic acid, while with non-basic 43 the ee was too low to detect. We proposed that the basic side chain delivered a proton to the decarboxylation intermediate in a stereoselective fashion. 

Some interesting applications of the conjugate addition of malonates to nitroolefins are the stereoselective synthesis of the antispastic agent (/ )-Baclofen [238b], and the antidepressant drug (/ )-rolipram, the latter obtained via highly stereoselective conjugate addition of a malonic acid half-thioester to a nitrostyrene derivative catalyzed by urea 154 [242],... 

If instead of malonic acid the ester with a lysine derivative is employed in the rearrangement (see 212), a series of unusual a-amino acids can be prepared stereoselectively (213) [78]. 

The reaction with monomethyl malonate in acetic acid, which does not occur at 0-10°C, proceeds smoothly when sonication is applied (Allegretti et al. 1993). From cyclohexene, only the cis ring fusion in bicyclic lactone is observed the product is formed at 80% yield for 15 min at 10°C. The overall transformation, in brief, is shown in Scheme 6.16. The stereoselectivity of the sonochemical process probably reflects the enhanced reaction rate, which does not allow equilibration processes to take place. 

The details of the polyketide pathway are on pp. 1425-30. The first addition is a decarboxylation of the malonate and a nucleophilic substitution on acetyl CoA in one step (in frame). After the addition of each unit, reduction to an alcohol (stereoselective), elimination to the unsaturated acid, and reduction to the saturated acid may occur. 

The first enantioselective total synthesis of (+)-macbecin I was accomplished by R. Baker and co-workers. A key vinyl iodide precursor was prepared stereoselectively using the malonic ester synthesis. Diethyl methylmalonate was treated with in situ generated diiodocarbene in ether at reflux to afford diiodomethylmethylmalonate in good yield. This dialkylated malonic ester then was converted to ( )-3-iodo-2-methyl-2-propenoic acid by reacting it with aqueous KOH. The saponification was accompanied by a concomitant decarboxylation. 

Obaza, J., Smith, F. X. A malonic ester synthesis with acid chlorides. The homologation of dioic acids. Synth. Common. 1982,12, 19-23. Sato, T., Otera, J. CsF in Organic Synthesis. Malonic Ester Synthesis Revisited for Stereoselective Carbon-Carbon Bond Formation. J. 

Analogous alkylations with unsaturated ketones can also be effected with silica-supported benzenesul-fonic acid sodium salt or, with some stereoselectivity, using a chiral imidazolidinone organo-catalyst. Optical induction can also be achieved in the addition of indole to alkyhdene malonates using bisoxazoline copper(II) complexes. ... 

The alkylidene-1,3-dicarbonyl moiety is also a highly reactive enophile. Thus, the Knoevenagel adduct (223) obtained from aldehyde (222) and dimethyl malonate in the presence of piperidinium acetate, cy-clizes by treatment with Lewis acids such as FeCb on AI2O3 exclusively to the rranr-substituted cyclohexane (224 trans.cis > 99.5 0.5 Scheme 44).7 °3 The sesquiterpene veticadinol (225) has been synthesized in enantiomerically pure form by this method.Contrary to the expectation, rranr-sub-stituted cyclopentanes can also be obtained with excellent induced and noninduced dia-stereoselectivities. Similarly, aldehydes containing an allylsilane moiety can be used for a highly stereoselective formation of rran.r-l,2-disubstituted cyclopentanes and cyclohexanes by a Knoevenagel... 

Activation of allylic ethers. An allylic ether y to an electron-withdrawing group is activated by forming the Fe(CO)4 complex. On acid treatment ionization occurs to generate the allyl cation (still complexed to iron), which is reactive towards nucleophiles such as silyl enol ethers, malonate ester enolates, etc. The substitution is stereoselective. ... 

As base. The 0-alkylation of tetronic acids and the alkylation of 2-pyridone (at O with primary halides and at N with secondary halides) are mediated by CsF. In each case the displacement of secondary mesylates with carboxylic acids and malonic esters proceeds stereoselectively using CsF as the base, thereby permitting the preparation of chiral substances. 

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