Trost’s ligand

Burke and Jiang have utilized Trost s ligand and the asymmetric ally lie alkylation to desymmetrize a tetraol diacetate as a potential route to a fragment of haU-chondrin B. Unfortunately, enantioselectivity was not determined in this reaction, although optical rotation suggests measurable selectivity ... 

A formal asymmetric nucleophilic addition to carbonyl compounds is achieved by Trost and his co-workers in the allylic alkylation of acylals of alkenals. An excellent enantioselectivity is observed in this alkylation. The starting acylals are easily prepared by the Lewis-acid catalyzed addition of acid anhydrides to aldehydes, by use of Trost s ligand 118 (Scheme 13), where various carbon-centered nucleophiles are available (Scheme l4),101,101a-10lc Asymmetric synthesis of some natural products is achieved according to this procedure. 

In 1992, Trost and his co-workers investigated desymmetrization of cyclic w j-o-diesters with lithium sulfonyl-methylenenitronate as a nucleophile in the presence of Trost s ligand 118, where the corresponding cyclic compounds are obtained with an excellent enantioselectivity via intramolecular cyclization (Scheme 15),103,103a Asymmetric cyclopropanation and lactone annulation are achieved according to this protocol (Scheme Nitroalkanes can also be employed as carbon-centered nucleophiles in lieu of malonates (Scheme 17). ... 

Trost and his co-workers succeeded in the allylic alkylation of prochiral carbon-centered nucleophiles in the presence of Trost s ligand 118 and obtained the corresponding allylated compounds with an excellent enantioselec-tivity. A variety of prochiral carbon-centered nucleophiles such as / -keto esters, a-substituted ketones, and 3-aryl oxindoles are available for this asymmetric reaction (Scheme jg) Il3,ll3a-ll3g Q jjg recently, highly enantioselective allylation of acyclic ketones such as acetophenone derivatives has been reported by Hou and his co-workers, Trost and and Stoltz and Behenna - (Scheme 18-1). On the other hand, Ito and Kuwano... 

The palladium catalyzed asymmetric hydroamination of cyclohexadiene with arylamines utilizing a variant of Trost s ligand R,R) 61 proceeds with high enantio selectivities under mild conditions (Scheme 11.19) [21]. The mechanism is believed to follow a similar pathway as proposed for palladium catalyzed hydroamination of vinyl arenes (Scheme 11.2) [17]. 

Burke and Jiang reported that the palladium-catalyzed diastereoselective double allylation of the diol bis(allylic acetate) 613 using (R,R) DPPBA 607 afforded the bis-tetrahydrofuran core 614 in 97% yield (Scheme 187).265 The resulting diene 614 was further transformed into a known intermediate 615 for the synthesis of uvaricin. They demonstrated that palladium (0)-catalyzed desymmetrization of the C2 diol 616 with Trost s ligand 607 afforded the tetrahy-drofuran 617 diastereoselectively (Scheme 188).266 The product 617 was manipulated to the F ring of halichondrin B (618). 

The group of Hartwig has shown that dienes imdergo hydroamination with anihnes in the presence of the palladium catalyst formed in situ from [ Pd( 7r-allyl)Cl 2] and Trost s ligand (2.190). Under optimum conditions cyclohexa-... 

As an alternative to this electrophilic activation/heterocyclization, Pd(0)-catalyzed intramolecular Tsuji—Trost reactions have been reported for the synthesis of THPs. For instance, in the presence of a Pd(0) complex and Trost s ligand [(R,R)-diphenylphosphino benzoic acid (DPPBA)]... 

The paUadium-catalyzed reactions occurred with the simple combination of [Pd(allyl) Cl]j and added phosphine, or with Pd(PPh3) and an acid co-catalyst. The scope of these reactions encompassed the additions of arylamines. As shown in Equation 16.81, reaction of various arylamines with cyclohexadiene occurred with high enantioselectivity using Trost s ligand. This ligand is discussed in more detail in Chapter 20. These reactions, and nickel-catalyzed reactions, occur by nucleophilic attack of amines on ir-allyl intermediates generated by protonation of diene complexes or insertion of dienes into palladium hydrides. 

The regioselectivity of palladium-catalyzed aUylic substitutions with heteroatom nucleophiles is often much different from that of reactions with carbon nucleophiles. In general, reactions of oxygen and nitrogen nucleophiles form more branched product than do reactions of carbon nucleophiles, at least as the kinetic product of substitution. For example, reactions of aryloxide nucleophiles with mono-substituted aUylic carbonates catalyzed by palladium complexes of Trost s ligand form more branched than linear product (Equation 20.32). Reactions of geminaUy disubstituted aUylic acetates with aziridines, hydroxylamine and hydrazine derivatives catalyzed by palladium complexes of bisphosphines form the branched prenyl product as the major isomer (Equations 2033a and 20.33b). " ... 

In contrast, especially to these diphenyl-substituted allylic substrates, the results obtained with cyclic substrates such as 55 were disappointing in the beginning. For example, when cyclohexenylacetate was treated with dimethyl malonate enolate in the presence of a PHOX ligand, no enantioselectivity was observed at all. However, by switching to other ligands, such as Trost s ligand, high enantiomeric excess values could be obtained also with cyclic allylic substrates (Scheme 12.28) [49]. 

However, after boron and tin enolates and their ate complexes had been successfully applied in the palladium-catalyzed allylic alkylation [9, 11], Trost and Schroeder reported in 1999 [12a] the first enantioselective catalytic variant wherein the tin enolate 13a derived from 2-methyl tetralone was reacted with allyl acetate. The use of the Cj-symmetric ligand (5, 5 )-14 ( Trost s ligand )... 

A remarkable kinetic resolution was observed recently by Feringa and coworkers when 2-silyloxyfuran was reacted with the racemic unsymmetrical allylic substrate 86, catalyzed by the palladium complex of Trost s ligand (/ ,/ )-14, as illustrated in Scheme 5.28. The acetate anion liberated upon oxidative addition of palladium(O) is assumed to cleave the silyl protecting group, so that the enolate anion forms aside from TMSOAc. After allylic alkylation of that enolate, double bond migration leads to butenolide (R)-87 isolated in 47%, if the reaction was run with 52% conversion. Not only the product 87 but also the recovered acetate... 

Enantioselective decarboxylative allylic alkylation was disclosed by several groups in the middle of the past decade [48]. An approach based on P-keto esters was first reported by Tunge and Burger and characterized as an asymmetric Claisen surrogate. Mainly esters with cyclic allyloxy moieties 99 were used. When the reaction was mediated by Trost s ligand R,R)-14, ketones... 

Furthermore, the decarboxylative allylic alkylation was extended to cyclic dienol carbonates 132 by Cossy and coworkers. Upon treatment with the palladium complex of Trost s ligand (U,U)-14, butenolides 133 with a quaternary stereogenic center were obtained in fair chemical and optical yields (Scheme 5.44) [64]. The preferred Si-face approach of the allylpalladium cation reaction is rationalized by an outer-sphere mechanism, adapting a transition state model related to that shown in Scheme 5.42. 

Direct aldol additions of ketones were also performed with a BINOL - diphenyl-prolmol catalyst, similar to Trost s ligand 290, and assumed to occur also through a zinc enolate [150]. In other protocols that use proline-derived amides, it remains uncertain whether a metal enolate is involved [151]. 

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