Pd-catalyzed asymmetric

Pd-catalyzed asymmetric allylic alkylation is a typical catalytic carbon-carbon bond forming reaction [ 126 -128]. The Pd-complex of the ligand (R)-3b bearing methyl, 2-biphenyl and cyclohexyl groups as the three substituents attached to the P-chirogenic phosphorus atom was found to be in situ an efficient catalyst in the asymmetric allylic alkylation of l-acetoxy-l,3-diphenylprop-2-en (4) with malonate derivatives in the presence of AT,0-bis(trimethylsilyl)acetamide (BSA) and potassium acetate, affording enantioselectivity up to 96% and quantitative... 

Scheme 30. Example of Pd-catalyzed asymmetric allylic alkylation...

As shown in Scheme 2.20, selective lithiation of substrate 2-87 by treatment with LDA in THF at -78 °C triggers an intramolecular Michael/intermolecular aldol addition process with benzaldehyde to give a mixture of diastereomers 2-90 and 2-91. 2-91 was afterwards transformed into 2-92, which is used as a chiral ligand for Pd-catalyzed asymmetric allylic substitution reactions [29]. 

Recent developments in Pd-catalyzed asymmetric H-Si addition are described in Sections... 

Figure 4.4. Proposed intermediate in Pd-catalyzed asymmetric 1,2-additions of acyl zirconocenes.

Related catalytic enantioselective processes It is worthy of note that the powerful Ti-catalyzed asymmetric epoxidation procedure of Sharpless [27] is often used in the preparation of optically pure acyclic allylic alcohols through the catalytic kinetic resolution of easily accessible racemic mixtures [28]. When the catalytic epoxidation is applied to cyclic allylic substrates, reaction rates are retarded and lower levels of enantioselectivity are observed. Ru-catalyzed asymmetric hydrogenation has been employed by Noyori to effect the resolution of five- and six-membered allylic carbinols [29] in this instance, as with the Ti-catalyzed procedure, the presence of an unprotected hydroxyl function is required. Perhaps the most efficient general procedure for the enantioselective synthesis of this class of cyclic allylic ethers is that recently developed by Trost and co-workers, involving Pd-catalyzed asymmetric additions of alkoxides to allylic esters [30]. 

The synthesis of lycorane (13) by Mori and Shiba-saki121 is breathtaking for its use of three consecutive Pd catalyzed C-C bond forming reactions. Thus, Pd-catalyzed asymmetric allylic substitution of a benzoate in meso 7 in the presence of the chiral bisphos-phine 8 leads to the regioselective formation of 10 in 40 % ee It is easy to overlook this low level of enantioselectivity when we are faced with the subsequent elegant Pd-catalyzed reactions Pd-catalyzed intramolecular animation is followed by a Pd-catalyzed Heck coupling to afford 12, which is then readily converted to the target molecule... 

Pd-catalyzed asymmetric alkylation is also used in the synthesis of chanodavine I by Genet... 

Scheme 2. Pd-catalyzed asymmetric allylic alkylation of 7 is followed by a Pd-catalyzed intramolecular C-N bond formation and a Pd-catalyzed intramolecular Heck-type alkylation in Mori and Shibasaki s total synthesis of lycorane (1995).

Significant developments in this area have been reported by Overman as well As illustrated in Scheme 5, a Pd-catalyzed asymmetric Heck reaction leads to the formation of cyclic amide 24 subsequent treatment with aqueous acid delivers 29 in 84 % yield and 93 % ee151 Optically pure 25 is obtined after recrystallization (80% recovery). Follow-up functionalization, shown in Scheme 5, affords either physostigmine 26 or physovenine 27 It is difficult to imagine an alternative, and nearly efficient or selective, approach to the construction of these target molcules. 

Scheme 17. Trost s total synthesis of pancrastatin chiral ligand 102 is utilized in a Pd-catalyzed asymmetric allylic alkylation (1995).

Chiral nonracemic bidentate 2-[o-(diphenylphosphino)phenyl]-5,6-dihydro-4//-l,3-oxazine derivatives proved to be effective P,N-ligands in Pd-catalyzed asymmetric transformations. When used in the Pd-catalyzed allylic alkylations of 1,3-diphenylallyl acetate with dimethyl malonate, phosphino-oxazines 147 and 148 and the... 

Whereas Pd-catalyzed asymmetric allylic substitution reactions, with carbon as well as with heteronucleophiles, are widespread in stereoselective catalysis, it seems unusual that sulfur nucleophiles are less commonly used. Therefore we tested our ligands in such a reaction. We employed ligands 2 and 3 successfully in the reaction of racemic 3-methoxycarbonyloxyhept-4-ene with lithium t-butylsulfinate in the presence of 1.5 mol% of Pd2dba3 and 4.5 mol% of the ligands. In all cases full conversion was achieved, but with marked differences in the product selectivities (Scheme 1.4.9, Table 1.4.7). 

Scheme 2,1,4,32 Pd-catalyzed asymmetric synthesis of allylic alcohols in the presence of bisphosphane 34,...

Scheme 3. Pd-catalyzed asymmetric cycloisomerization with c/s-bidentate ligands.

Raluy E, Dieguez M, Pamies O (2007) Sugar-based diphosphoroamidite as a promising new class of ligands in Pd-catalyzed asymmetric allylic alkylation reactions. J Org Chem 72 2842-2850... 

Scheme 3 NHC/Pd-catalyzed asymmetric allylic substitution with dimethyl malonate...

The conversion of racemic butadiene monoepoxide to a single enantiomer of 54 (R=CH2OH) using Pd-catalyzed asymmetric allylic alkylation was uncovered by Trost [141]. By using a slightly modified ligand, the alkylation with phthalim-... 

Recently, Trost reported an efficient Pd-catalyzed asymmetric allylic alkylation of 1-tetralones [175] and a-arylketone 83 creating a quaternary center as exemplified by the synthesis of 84 (Scheme 7) [176]. Two a-heterocyclic ketones were also alkylated with similar results. Ferrocene-based ligands are effective in pro-... 

Although mechanistic details are not very clear, a recently reported Pd-catalyzed asymmetric ene reaction may proceed via hydropalladation-initiated asymmetric Heck reaction [80] (Scheme 22). 

A novel Pd-catalyzed asymmetric annulation was reported between 5-bromopyrrole-2-carboxylate esters and vinyl aziridines <07OL2357>. The resulting pyrrolopiperazinones such as 58 served as key intermediates in the enantioselective synthesis of longamide B and a number of other pyrrole alkaloids. 

Formic acid is also effective in the Pd catalyzed asymmetric reduction of ester functions R—0C02Me to R—H (R = chiral allyl group).27... 

Recently Trost et al. succeeded in the total synthesis of (+)-agelastatin A using Pd-catalyzed asymmetric allyUc alkylations [71]. In the course of this study they prepared piperazinone 98 which was amenable to allylic amina-tion via sulfodiimide 78 (Scheme 25). In the context of Weinreb s synthesis the authors claim 99 to be a suitable intermediate for the synthesis of the (-)-enantiomer of agelastatin A. 

BINAP-Pd Catalyzed Asymmetric Reactions. BINAP-Pd complexes are prepared in situ from Bis(dibenzyl-ideneacetone)palladium(0) or Pd2(dba)3 CHCI3 and BINAP. BINAP-Pd complexes are formed from Bis(allyl)di-p.-chlorodipalladium, Palladium(II) Acetate, or PdCl2(MeCN)2 and BINARY " ... 

Abe, H., Amii, H. and Uneyama, K. (2001) Pd-catalyzed asymmetric hydrogenation of a-fluo-rinated iminoesters in fluorinated alcohol a new and catalytic enantioselective synthesis of fluoro a-amino acid derivatives. Org. Lett., 3, 313-315. 

In the last decade there have been remarkable advances in the syntheses and applications of optically active a-chiral allylsilanes. Asymmetric hydrosilylation of 1,3-dienes provides convenient access to these allylsilanes [387]. Hayashi et al. have demonstrated tliat axially chiral monophosphines (MOP) are efficient chiral ligands in the Pd-catalyzed asymmetric hydrosilylation [388]. In particular, the MOP ligand 124 can realize high catalytic activity and enantioselectivity in the reaction of cyclic 1,3-dienes with HSiCL (Scheme 10.137) [388a,b]. The allyltrichlorosilanes obtained are quite valuable for highly diastereo- and enantioselective allylation of aldehydes by Kobayashi s procedure [371]. 

Optically active allenyltrichlorosilanes can be prepared by the Pd-catalyzed asymmetric hydrosilylation of 1,3-enynes with I ISiCb, (Scheme 10.138) [389]. In this reaction use of bisPPFOMe (125) as the chiral ligand achieves high enantioselectivity. The allenylsilanes smoothly react with PhCHO in DMF to give optically active homopropargyl alcohols, and the axial chirality of allenylsilanes is completely transferred to the central chirality of the products by a syn-SE process. 

A number of homogeneous chiral ligands have been developed for the Pd-catalyzed asymmetric allylic subshtuhon reachon, which is one of the useful methods for asymmetric C-C and C-X bond formahon [59]. Although several of Pd-catalyzed asymmetric allylic substituhons have been investigated in ionic... 

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