Asymmetric palladium-mediated

H. Yoshizake, H. Satoh, Y., Satoh, S. Nukui, M. Shibasaki, M. Mori, Palladium-Mediated Asymmetric Synthesis of Cfs-3,6-Disubstituted Cydohexenes. A Short Total Synthesis of Optically Active (+)-Y-Lycorane , J. Org Chem 1995, 60, 2016-2021. 

N-Arylation of various azoles (or their anions) was readily accomplished with p-tolyllead triacetate in the presence of copper(II)acetate [95JOC5678] however, die applicability of this procedure to other aryllead triacetates was not discussed. Solvent-dependent palladium-mediated allylations [95JHC1325] and Mitsunobu-based asymmetric alkylations [95JOC2008] of imidazoles and benzimidazoles have also been reported. 

Mizorokf and Heck reported independently in the early 1970s the first palladium-mediated coupling of an aryl or vinyl halide or triflate with an alkene. This reaction is generally referred to as the Heck reaction. From the first reports on asymmetric intramolecular Heck reactions by Overman and Shibasakf in 1989 the asymmetric Heck reaction has emerged as a reliable method for the stereoselective formation of tertiary and quaternary stereogenic centers by C-C bond formation in polyfunctionalized molecules. ... 

Saitoh, A., Achiwa, K., Tanaka, K., Morimoto, T. Versatile Chiral Bidentate Ligands Derived from a-Amino Acids Synthetic Applications and Mechanistic Considerations in the Palladium-Mediated Asymmetric Allylic Substitutions. J. Org. Chem. 2000, 65, 4227 240. 

A. Saitoh, K. Achiwa, K. Tanaka, and T. Morimoto, Versatile chiral bidentate ligands derived from a-amino acids. Synthetic applications and mechanistic considerations in palladium-mediated asymmetric allylic substitutions, J. Org. Chem., 65 (2000) 4227-4243. 

The palladium-mediated [3 + 2] cycloaddition is a stereospecific cis addition with retention of the alkene geometry. With chirally modified (E)- and (Z)-crotonates diastereoselective asymmetric induction is observed, with the Z-isomer showing a much higher diastereofacial selectivity32. A similar asymmetric induction occurs with chirally modified sulfones15. 

An obvious extension of the AD-process would be the asymmetric transfer of heteroatoms other than oxygen to a carbon carbon double bond. Indeed, the osmium catalyzed [3] or palladium mediated [4] aminohydroxylation of alkenes has been known for 20 years. The resulting jff-amino alcohols are an important structural element in biologically active compounds as well as the starting point in the design of many chiral ligands. However, to develop this reaction into a catalytic, asymmetric process several problems had to be overcome. 

A new class of chiral amidine-phosphine and -sulfide hydrid ligands with a variety of modifications is used for the palladium mediated allylic substitutions of both acyclic and cyclic compounds [74] (Figure 3.5). High levels of asymmetric induction were achieved for both substrates. 

Merging chemical synthesis and biosynthesis as a strategy of the total synthesis of natural products and natural product libraries 12AG(E)4012. Palladium-mediated total synthesis ofbioactive natural products 13S1271. Recent contributions from the asymmetric aza-Michael reaction to alkaloids total synthesis 13NPR1211. 

The palladium-mediated cross-coupling of organozinc reagents, derived from the asymmetric carboalumination of allyl alcohol, with (iodoethynyl)trimethylsilane (eq 9), has also been reported en route to callystatin... 

Another enantioselective route to 116, that features catalytic asymmetric induction, is shown here (see Prostaglandins-12 for another example). This synthesis begins with racemic allylic acetate 123. A palladium-mediated ally-lation of dimethyl malonate in the presence of chiral ligands (for the Pd) provided 124 with excellent enantioselectivity. This material was converted to 116. Alkylation as per the Mori synthesis (Juvabione-16) gave 117, which was converted to 125 using another Pd-mediated malonate allylation. Malonate 125 was converted to 126 via an intermediate tetraol. The synthesis of juvabione (15) was then completed using a short reaction sequence. 

Zinc enolates like 41 served as nucleophiles in a study aimed at a rhodium-catalyzed reaction with enantiomerically enriched allylic phosphates. Nonracemic products were obtained under efficient chirality transfer from the substrate and with remarkable diastereoselectivity [23]. Kazmaier enolates were used to manipulate the backbone of small peptides [27] by palladium-catalyzed allylations of a terminal glycine ester [28]. In the course of these studies, central glycine was also allylated in a diastereoselective manner through assumed chelated zinc enolates of glycine in a peptidic bond to proline or JV-alkyl amino acids [29]. Although this is, of course, not an asymmetric synthesis, the protocol is remarkable inasmuch as, in contrast to the palladium-mediated conversion, the noncatalyzed reaction of the enolate with the corresponding allylic bromide occurs in a more or less stereorandom manner. 

Yoshizaki H, Satoh H, Sato Y, Nukui S, Shibasaki M, Mori M. Palladium-mediated asymmetric synthesis of cis-3,6-disubstituted cyclohexenes. A short total synthesis of optically active (- -)-7-lycorane. J. Org. Chem. 1995 60(7) 2016-2021. 

Recently, Ogasawara and co-workers [54] disclosed an efficient synthesis of tiie enantiomerically pure tricyclic dienone 222 in both enantiomeric forms by employing lipase-mediated asymmetrization of the meso-synunetric precursor, and the novel palladium-mediated elimination reaction of the chiral monoacylated product. With this they show a new synthetic approach to A-ring synthon 189c (Scheme 13) [55]. Treatment of tricyclic diol 220, obtained from reduction of diketene 219, with two equivalents of vinyl acetate in acetonitrile in the presence of PSL furnished the monoacetate 221 in 79% yield after being stirred for 16 days at 28 C. The optically active acetate 221 was treated with ammonium formate in the presence of catalytic amounts of PdCl2(PPh3)2 to furnish the... 

In 2003, Bonini et al. reported a new synthesis of ferrocenyloxazolines based on an iodide-mediated ring expansion of A-ferrocenoyl-aziridine-2-carboxylic esters. The thus-formed ligands were successfully employed as palladium chelates for the test reaction, since they allowed the product to be formed in quantitative yields and good to high enantioselectivities (Scheme 1.69). According to the results, it seemed that the additional chiral centre present in the oxazoline backbone of these ligands did not play a major role for the asymmetric induction and the activity of the corresponding catalysts. 

Radical cyclization of polyfunctional 5-hexenyl halides mediated by Et2Zn and catalyzed by nickel or palladium salts has been demonstrated to produce stereoselectively polyfunctional 5-membered carbo- and heterocycles [56, 57]. Based on this strategy a formal synthesis of methylenolactocin (11) was achieved (Scheme 20). The acetal 130, readily being built up by asymmetric alkylation of aldehyde 127 followed by reaction with butyl vinyl ether and NBS, served as the key intermediate for the construction of the lactone ring. Nickel(II)-catalyzed carbometallation was initiated with diethylzinc to yield exclusively the frans-disubstituted lactol 132, which could be oxidized directly by air to 134. Final oxidation under more forcing conditions then yielded the lactone (-)-75 as a known intermediate in the synthesis of (-)-methylenolactocin (11) [47aj. 

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