Sequential catalytic isomerization and allylic substitution. Conversion of racemic branched allylic carbonates to enantioenriched allylic substitution products

A catalytic protocol for the conversion of readily accessible racemic, branched aromatic allylic esters to branched allylic amines, ethers, and alkyls has been developed. Palladium-catalyzed isomerization of branched allylic esters to terminal allylic esters, followed by sequential iridium-catalyzed allylic substitution, gave the branched allylic products in good yield with high regioisomeric and enantiomeric selectivity. Both electron-rich and electron-poor branched allylic esters gave products in >90% ee. High enantiomeric excesses were also observed for the products from the reactions of 2-thienyl acetates and dienyl carbonates.     

Retention of regiochemistry and chirality in the ruthenium catalyzed allylic alkylation of disubstituted allylic esters

The regiospecific nucleophilic substitution during the ruthenium catalyzed allylic alkylation of 1,3-unsymmetrical disubstituted allylic esters was demonstrated. The nucleophile was selectively introduced at the position originally substituted with leaving group in the 2-DPPBA or ip-pybox ligated [RuCl(2)(p-cymene)](2) catalyzed allylic alkylation of 1,3-unsymmetrical disubstituted allylic esters. The chirality of the optically active allylic esters was also transferred to the alkylated products.     

Conjugate addition of allylic lithium organocuprates and allylic organocopper(I) compounds to α-acetylenic esters

at low temperature, allylic lithium organocuprates and allylic organocopper(I) compounds add stereoselectively (cis-addition) to α-acetylenic esters to afford α,δ-biethylenic esters.     

Pd-catalyzed olefination of furans and thiophenes with allyl esters

A direct Pd(II)-catalyzed olefination of furans and thiophenes with allyl esters is demonstrated. Under the typical conditions, the dehydrogenative Heck coupling reactions of heteroarenes with allylic esters proceeded via a β-H elimination rather than a β-OAc elimination to give the corresponding γ-substituted allylic esters.     

Reactions of Isatin Dimethyl Ketal and Its Ethyl Imino Ether with Methyllithium

Although allylic thiocyanates undergo a facile thermal (3,3) isomerization to form the more stable allylic isothiocyanates¹, this transformation has played a surprisingly minor role in organic synthesis. We have found that α,β-unsaturated esters (1) can be converted to α-isothiocyanatoacrylic esters (2) via an allylic (3,3) thiocyanate isomerization.     

Geminal dicarboxylates as carbonyl surrogates for asymmetric synthesis. Part II. Scope and applications.

An enantioselective synthesis of allylic esters has been achieved by a novel asymmetric alkylation of allylic gem-dicarboxylates. The catalyst derived from palladium(0) and R,R-1,2-di(2'-diphenylphosphinobenzamido)cyclohexene efficiently induced the alkylation process with a variety of nucleophiles to provide allylic esters as products in good yield. High regio- and enantioselectivities were observed in the alkylation with most nucleophiles derived from malonate, whereas a modest level of ee's was obtained in the reactions with less reactive nucleophiles such as bis(phenylsulfonyl)ethane. In the latter case, a slow addition procedure proved effective, leading to significantly improved ee's. The utility of the alkylation products was demonstrated by several synthetically useful transformations including allylic isomerizations, allylic alkylations, and Claisen rearrangements. Using these reactions, the chirality of the initial allylic carbon-oxygen bond could be transferred to new carbon-oxygen, carbon-carbon, or carbon-nitrogen bonds in a predictable fashion with high stereochemical fidelity. The conversion of gem-diesters to chiral esters by the substitution reaction is the equivalent of an asymmetric carbonyl addition by stabilized nucleophiles. In conjunction with the subsequent reactions that occur with high stereospecificity, allylic gem-dicarboxylates serve as synthons for a double allylic transformation.     

Pd-catalyzed olefination of perfluoroarenes with allyl esters

An efficient Pd(II)-catalyzed direct olefination of perfluoroarenes with allyl esters is demonstrated. Under the typical conditions, the coupling reaction of fluorinated-arenes with allylic esters proceeded via a β-H elimination rather than a β-OAc elimination to give the corresponding γ-substituted allylic esters.     

Palladium-catalyzed regio- and stereoselective formate reduction of fluorine-containing allylic mesylates. A new entry for the construction of a tertiary carbon attached with a fluoroalkyl group

The regioselective palladium-catalyzed formate reduction of gamma-fluoroalkylated allylic esters is described. Reduction of the allylic esters under the influence of palladium with a monodentate phosphine ligand proceeded preferentially at the gamma position, the corresponding reduction products with a fluoroalkyl group at the tertiary carbon being afforded in high yields. When the chiral allylic ester was employed, complete chirality transfer was observed, leading to the optically active materials in high yields.     

三异丙氧钐催化下β-酮酸烯丙酯的合成

在甲苯中，以Sm(i-PrO)~3(10%)为催化剂，β-酮酸乙酯与烯丙醇进行酯交换反应得到中等产率的β-酮酸烯丙酯。     

Application of the Ester Enolate Claisen Rearrangement in the Synthesis of Amino Acids Containing Quaternary Carbon Centers

Ester enolate Claisen rearrangement of highly substituted amino acid allylic esters 4 allows for the synthesis of sterically demanding amino acids 5 with beta-quaternary carbon centers. Because of enolate fixation by chelation, the rearrangement occurs in a highly diastereoselective fashion. The methodology is suitable not only for glycine derivatives but also for allylic esters of various amino acids. In this case amino acids with two vicinal quaternary carbon centers are created. With unsymmetrically substituted allylic esters like 4k-n the rearrangement proceeds with a high degree of diastereoselectivity.     

Palladium-catalyzed reactions of hypophosphorous compounds with allenes, dienes, and allylic electrophiles: methodology for the synthesis of allylic h-phosphinates

Hypophosphorous compounds (MOP(O)H(2), M = H, R(3)NH) effectively participate in metal-catalyzed C-P bond-forming reactions with allenes, dienes, and activated allylic electrophiles under mild conditions. The catalytic system Pd(2)dba(3)/xantphos is crucial to avoid or minimize the competitive reductive transfer-hydrogenation pathway available to hypophosphorous acid derivatives. Further investigation into the allylation mechanism provided access to the analogy allylic acetate-allylic phosphinate, which then led to the development of a Pd-catalyzed rearrangement of preformed allylic phosphinates esters and, ultimately, to a catalytic dehydrative allylation of hypophosphorous acid with allylic alcohols. The reactions disclosed herein constitute efficient synthetic approaches, not only to prepare allylic H-phosphinic acids but also their esters via one-pot tandem processes. In addition, the potential of H-phosphinates as useful synthons for the preparation of other organophosphorus compounds is demonstrated.     

Synthesis of enantioenriched tertiary boronic esters from secondary allylic carbamates. Application to the synthesis of C30 botryococcene

Enantioenriched secondary allylic carbamates have been deprotonated with sBuLi and reacted with boronic esters. In contrast to other electrophiles, high α-selectivity was observed and the boronate complexes were formed with almost complete retention of stereochemistry. The boronate complexes underwent a stereospecific 1,2-migration leading to tertiary allylic boronic esters with high er (>98:2). The scope of the reaction has been explored and found to embrace a broad range of both allylic carbamates and boronic esters. The methodology has been applied to an eight-step, stereoselective synthesis of each of the diastereoisomers of C30 botryococcene.     

Tetrabutylammonium iodide catalyzed synthesis of allylic ester with tert-butyl hydroperoxide as an oxidant

A metal-free C-H oxidation for the construction of allylic esters has been developed. The use of a commercially available and inexpensive catalyst and oxidant, and readily available starting materials, coupled with the operational simplicity of the reaction, renders the methodology a useful alternative to other approaches typically employed in the synthesis of allylic esters.     

Highly Selective Allylborations of Aldehydes Using α,α‐Disubstituted Allylic Pinacol Boronic Esters

α,α‐Disubstituted allylic pinacol boronic esters undergo highly selective allylborations of aldehydes to give tetrasubstituted homoallylic alcohols with exceptional levels of anti‐Z‐selectivity (>20:1). The scope of the reaction includes both acyclic and cyclic allylic boronic esters which lead to acyclic and exocyclic tetrasubstituted homoallylic alcohols. The use of β‐borylated allylic boronic esters gave fully substituted alkenes bearing a boronic ester which underwent further cross‐coupling enabling a highly modular and stereoselective approach to the synthesis of diaryl tetrasubstituted alkenes. Computational analysis revealed the origin of the remarkable selectivity observed.     

Palladium-catalyzed and organozinc-promoted synthesis of dienes from allylic esters possessing an acyloxy or alkoxy group

Organozinc and a Pd catalyst promoted formation of dienes from allylic esters possessing a leaving group such as acyloxy and alkoxy groups next to the allyl moiety. The reaction proceeded with high regio- and stereoselectivity when applied to secondary allylic substrates.     

Claisen rearrangements of equilibrating allylic azides

Equilibrating mixtures of allylic azide-containing allylic alcohols or allylic 2-tolylsulfonylacetic esters undergo Johnson-Claisen or Ireland-Claisen rearrangement reactions to give unsaturated γ-azidoesters and -acids, respectively. Decarboxylation of the acids under basic conditions gives azidosulfones, with moderate to high diastereoselectivity.     

A novel and efficient procedure for the preparation of allylic alcohols from α,β-unsaturated carboxylic esters using LiAlH4/BnCl

A new and efficient method for the reduction of α,β-unsaturated carboxylic esters to allylic alcohols utilizing LiAlH₄/BnCl is described. Various α,β-unsaturated esters, including the coumarins bearing α,β-unsaturated lactone skeleton, can be converted smoothly into their corresponding allylic alcohols in high yields under mild conditions with short reaction times.     

Cu(I)-catalyzed, α-selective, allylic alkylation reactions between phosphorothioate esters and organomagnesium reagents

Regiocontrol of allylic alkylation reactions involving hard nucleophiles remains a significant challenge and continues to be an active area of research. The lack of general methods in which α-alkylation is favored underscores the need for the development of new processes for achieving this type of selectivity. We report that Cu(I) catalyzes the allylic substitution of phosphorothioate esters with excellent α-regioselectivity, regardless of the nature of the Grignard reagent that is used. To the best of our knowledge, the Cu-catalyzed allylic alkylation of phosphorothioate esters has never been described. We have also developed a simple protocol for inducing high α selectivity starting from secondary allylic halides. This is accomplished by using sodium phosphorothioates as an additive.     

Mesyloxy-group migration as the stereoselective preparation method of various functionalized olefins and its reaction mechanism

[structure: see text]. It was demonstrated that mesylation of appropriate gamma,gamma-difluorinated allylic alcohols under usual conditions furnished the corresponding alpha,alpha-difluorinated allylic mesylates, possibly by way of 1,3-mesyloxy-group migration after formation of the expected "normal" intermediates, gamma,gamma-difluorinated allylic mesylates. This rearrangement was conveniently applied to the construction of trisubstituted allylic alcohols, alpha,beta-unsaturated esters, amides, or ketones in good to excellent chemical yields with exclusive E selectivities.     

Phosphine-catalyzed allylic substitution of Morita-Baylis-Hillman acetates: synthesis of N-protected beta-aminophosphonic acid esters

A series of N-protected beta-amino phosphonic acid esters have been prepared by phosphine-catalyzed allylic substitution of 2-(diethylphosphonyl)-substituted allylic acetates employing 4,5-dichlorophthalimide as nucleophilic partner. These organocatalytic allylic substitutions exhibit exceptionally high levels of regiospecificity by virtue of a tandem S(N)2'-S(N)2' mechanism.