Decarboxylation stereoselective

The preparation of ketones and ester from (3-dicarbonyl enolates has largely been supplanted by procedures based on selective enolate formation. These procedures permit direct alkylation of ketone and ester enolates and avoid the hydrolysis and decarboxylation of keto ester intermediates. The development of conditions for stoichiometric formation of both kinetically and thermodynamically controlled enolates has permitted the extensive use of enolate alkylation reactions in multistep synthesis of complex molecules. One aspect of the alkylation reaction that is crucial in many cases is the stereoselectivity. The alkylation has a stereoelectronic preference for approach of the electrophile perpendicular to the plane of the enolate, because the tt electrons are involved in bond formation. A major factor in determining the stereoselectivity of ketone enolate alkylations is the difference in steric hindrance on the two faces of the enolate. The electrophile approaches from the less hindered of the two faces and the degree of stereoselectivity depends on the steric differentiation. Numerous examples of such effects have been observed.51 In ketone and ester enolates that are exocyclic to a conformationally biased cyclohexane ring there is a small preference for... 

The stereoselective total synthesis of (+)-epiquinamide 301 has been achieved starting from the amino acid L-allysine ethylene acetal, which was converted into piperidine 298 by standard protocols. Allylation of 297 via an. V-acyliminium ion gave 298, which underwent RCM to provide 299 and the quinolizidine 300, with the wrong stereochemistry at the C-l stereocenter. This was corrected by mesylation of the alcohol, followed by Sn2 reaction with sodium azide to give 301, which, upon saponification of the methyl ester and decarboxylation through the Barton procedure followed by reduction and N-acylation, gave the desired natural product (Scheme 66) <20050L4005>. 

Several examples of transition metal catalysis for the synthesis of piperidines appeared this year. Palladium catalyzed intramolecular urethane cyclization onto an unactivated allylic alcohol was described as the key step in the stereoselective synthesis of the azasugar 1-deoxymannojirimycin . A new synthetic entry into the 2-azabicyclo[3.3.1]nonane framework was accomplished through a palladium mediated intramolecular coupling of amine tethered vinyl halides and ketone enolates in moderate yields . A palladium catalyzed decarboxylative carbonylation of 5-vinyl... 

Decarboxylation of p-lactones to olefins,4 6 stereoselective reactions of p-lactones with a variety of electrophiles,6 9 and the regioselective fission of p-lactones by many different nucleophiles10 12 make these highly reactive compounds versatile intermediates for organic syntheses.13 Although several methods exist for the preparation of p-lactones, most p-lactones are now synthesized by [2+2] cycloaddition... 

In addition to the two asymmetric syntheses above described, two racemic syntheses of tetraponerines based on the 5=6-5 tricyclic skeleton have been published. Thus, Plehiers et al. [199] have reported a short and practical synthesis of ( )-decahydro-5Tf-dipyrrolo[l,2-a r,2/-c]pyrimidine-5-carbonitrile (238), a pivotal intermediate in the synthesis of racemic tetraponerines-1, -2, -5 and -6, in three steps and 24% overall yield from simple and inexpensive starting materials. The key reaction of the synthesis was a one-pot stereoselective multistep process, whereupon two molecules of A pyrroline react with diethylmalonate to afford the tricyclic lactam ester 239, possessing the 5-6-5 skeleton (Scheme 10). Hydrolysis of the carboethoxy group of 239 followed by decarboxylation yielded lactam 240, that was converted into a-aminonitrile 238 identical in all respects with the pivotal intermediate described by Yue et al. [200] in their tetraponerine synthesis. 

Fig. 45 Stereoselective methoxylation of serine derivatives by anodic decarboxylation [223].

Birch reduction-alkylation of 5 with 2-bromoethyl acetate was carried out with complete facial selectivity to give 57. This tetrafunctional intermediate was converted to the bicyclic iodolactone 58 ( > 99% ee) from which the radical cyclization substrate 59 was prepared. The key radical cyclization occurred with complete regio- and facial-selectivity and subsequent stereoselective reduction of the resulting tertiary radical gave 60 with the required trans BC ring fusion.The allylic alcohol rmit of (+)-lycorine was obtained by a photochemical radical decarboxylation, 62 63. 

Serine hydroxymethyl transferase catalyzes the decarboxylation reaction of a-amino-a-methylmalonic acid to give (J )-a-aminopropionic acid with retention of configuration [1]. The reaction of methylmalonyl-CoA catalyzed by malonyl-coenzyme A decarboxylase also proceeds with perfect retention of configuration, but the notation of the absolute configuration is reversed in accordance with the CIP-priority rule [2]. Of course, water is a good proton source and, if it comes in contact with these reactants, the product of decarboxylation should be a one-to-one mixture of the two enantiomers. Thus, the stereoselectivity of the reaction indicates that the reaction environment is highly hydro-phobic, so that no free water molecule attacks the intermediate. Even if some water molecules are present in the active site of the enzyme, they are entirely under the control of the enzyme. If this type of reaction can be realized using synthetic substrates, a new method will be developed for the preparation of optically active carboxylic acids that have a chiral center at the a-position. 

Ikegami has devised an interesting approach based upon 1,3-cyclooctadiene monoepoxide as starting material (Scheme LX) Transannular cyclization, Sharpless epoxidation, and silylation leads to 638 which is opened with reasonable regioselec-tivity upon reaction with l,3-bis(methylthio)allyllithium. Once aldehyde 639 had been accessed, -amyllithium addition was found to be stereoselective, perhaps because of the location of the te -butyldimethylsilyloxy group. Nevertheless, 640 is ultimately produced in low overall yield. This situation is rectified in part by the initial formation of 641 and eventual decarboxylative elimination of 642 to arrive at 643. An additional improvement has appeared in the form of a 1,2-carbonyl transposition sequence which successfully transforms 641 into 644... 

The diacetate of 711 has also been produced in stereoselective fashion via a route beginning with dicyclopentadiene (Scheme LXXVI) Ketone 712 was transformed into dimethylated alcohol 713 whose ozonolysis provided 714. Following Jones oxidation, decarboxylation with concomitant introduction of a double bond was realized by application of Kochi s prowdure. A lengthy quence of steps to adjust functionality led up to annulation by a modified Wichterle sequence. The conversion of 715 to 716 was accomplish by standard reactions. 

Racemic jS-fluoroalkyl tyrosines and phenylalanines have been prepared by classical methods starting from the corresponding fluoroacetophenones. Synthesis of the nonracemic compounds is much more difficult, as exemplified by the preparation of jS-difluoromethyl meta-tyrosines (Figure 5.14). jS-Trifluoromethyl tryptophan is prepared by alkylation of ethyl acetamido malonate with indolyl-2,2-trifluoroethanol. Surprisingly, the decarboxylation reaction leads stereoselectively to the syn isomer (Figure 5.15). ... 

Eollowing a radical process, radiation induced chain addition of allylbenzene to 1,4-dioxane 16. Efficiency of the addition depends on the concentration of the monomer <1999JRN953>. Alcohols also react, albeit in low yields (10%), with 16 in the presence of (diacetoxyiodo)benzene, probably via a radical pathway, to afford 2-alkoxy-l,4-dioxanes <2004SL2291 >. Free radicals have also been generated by decarboxylation of dimethoxydioxanecarboxylic acids 101 and added to some maleimides and acrylates with high stereoselectivity (Scheme 9) <20020L2035>. 

Asymmetric synthesis is any synthesis that produces enantiomerically or diastereomeri-cally enriched products. This is the expected result if enantiomerically enriched chiral substrates are employed. Of interest here are asymmetric syntheses where the reactants are either achiral or chiral but racemic. Many examples of this type are collected in volumes edited by Morrison [33]. The first example of an asymmetric synthesis involved use of the chiral, optically pure base brucine in a stereoselective decarboxylation of a diacid with enantiotopic carboxyl groups [34] ... 

Palladium-catalyzed coupling of allylic acetate 113 (Scheme 23) with diethyl malonate, or with acetylated diethyl tartronate, yielded the Boc-protected allylic amines 114 in 99 1 E stereoselectivity.1 "1 Saponification of 114 (R1 = H) and decarboxylation gave the Tyr- Ala alkene isostere 116 in quantitative yield, whereas 114 (R = OAc) was converted into the Tyr-Gly alkene isostere 115 in a two-step procedure in 62% overall yield. Considering the number of steps and the overall yield, this procedure is among the most efficient to prepare Xaatp, CH=CH]Gly dipeptide isosteres. 

The intermediary cofactor bound acetyl anion equivalent can be transferred to an aldehyde acceptor, e.g. to acetaldehyde already produced during regular catalytic reaction in which optically active 3-hydroxy-2-butanone (acetoin, an important aroma constituent) is formed. Interestingly, PDCs from different sources differ in stereoselectivity [443] acetoin (I )-143 is obtained using brewer s yeast PDC (ee 28-54%) [444,445] while the enantiomeric (S)-143 is produced preferentially by PDC from wheat germ (ee 16-34%) [446] or from Z. mobilis (ee 24-29%) [445], When glyoxylate 14 (instead of 2) is subjected to decarboxylation in the presence of acetaldehyde, optically active lactaldehyde... 

---