Palladium-catalyzed asymmetric allylic alkylations

Enantio- and diastereoselective syntheses of a variety of heterocycles were accomplished by combining the ruthenium-catalyzed Alder-ene reaction with a palladium-catalyzed asymmetric allylic alkylation (AAA) (Scheme 7). For the AAA, y>-nitrophenol was found to function as a suitable leaving group and yet was stable to the Alder-ene conditions. Extensive solvent studies were performed to determine the best conditions for the one-pot procedure. 

Acylals (geminal diacetates) are frequently used as protecting groups for aldehydes because of their stability to neutral and basic conditions [8]. In addition, the acylal functionality can be converted into other useful functional groups [9]. For example a novel synthesis of chiral allylic esters has been developed using palladium-catalyzed asymmetric allylic alkylation of gem-diesters [10]. The allylation of... 

Ethylene-bridged bissulfoximines 55 have also been applied in palladium-catalyzed asymmetric allylic alkylations affording products with up to 98% ee see C. 

Figure 8.9 Results of palladium-catalyzed asymmetric allylic alkylation of 1,3-di phenyl al lyl acetate and dimethyl malonate upon applying a ligand library of self-assembled bidentate ligands. The ligands a-i on the x-axis are defined in Figure 8.8. 

While alkyl halides are typically employed as an electrophile for this transformation, Takemoto developed palladium-catalyzed asymmetric allylic alkylation of 1 using allylic acetates and chiral phase-transfer catalyst 4k, as depicted in Scheme 2.5 [ 2 3 ]. The choice of triphenyl phosphite [(PhO)3P] as an achiral palladium ligand was crucial to achieve high enantioselectivity. 

Takemoto and coworkers extended their palladium-catalyzed asymmetric allylic alkylation strategy using allyl acetate and chiral phase-transfer catalyst to the quaternization of 13 [23b]. A correct choice of the achiral palladium ligand, (PhO P, was again crucial to achieve high enantioselectivity and hence, without chiral phosphine ligand on palladium, the desired allylation product 15 was obtained with 83% ee after hydrolysis of the imine moiety with aqueous citric acid and subsequent benzoylation (Scheme 2.12). 

Several enantioselective approaches to vitamin E (1), based on resolution of the products, the use of enantiopure natural building blocks, auxiliary controlled reactions and asymmetric oxidations have been described. In addition, a palladium-catalyzed asymmetric allylic alkylation reaction to build up the chiral chroman framework has been employed by Trost. Tietze and coworkers have developed asymmetric syntheses of the chiral chroman moiety using either the selective ally-lation of an alkyl methyl ketone or a Sharpless dihydroxylation as the key step. However, none of these methods is efficient enough for an industrial approach. ... 

Palladium-catalyzed asymmetric allylic alkylation [529] of suitable amines with two equivalents of racemic butadiene monoxide ((-r)-411) allows for the expedient synthesis of trans-and cA-2,5-dihydropyrroles derivatives 416 and 417 that are versatile chrrons towards the s)m-thesis of a wide variety of iminosugars [530]. In the presence of 0.4% [(allyl)PdCl)2], 1.2% of enantiomerically pure diphosphine (/ ,/ )-ligand, and Na2C03 a 1 1 mixture of ( )-411 and phthalimide reacted in CH2CI2 at room temperature giving (5)-412 in 99.6% yield and... 

Kaiser, N. F. K., Bremberg, U., Larhed, M., Moberg, C., Hallberg, A. Microwave-mediated palladium-catalyzed asymmetric allylic alkylation an example of highly selective fast chemistry. J. Organomet. Chem. 2000, 603, 2-5. 

In 2002, Trost and Tang reported the chiral total synthesis of (-)-codeine in short reaction steps using a palladium-catalyzed asymmetric allylic alkylation (AAA) [53] as the key transformation [54], In 2005, a detailed full account of their synthesis was published [55]. The key features of their synthesis are (1) a preparation of an aryl ether with high optical purity by the Pd-catalyzed AAA reaction, (2) the intramolecular Heck reaction to generate the A-C-E benzofuran skeleton, (3) the second intramolecular Heck reaction of Z-vinyl bromide providing the phenan-throfuran core, and (4) the intramolecular hydroamination for the construction of D-ring by the action of LDA and visible light. 

Mino et al. recently reported the synthesis of optically pure phosphine ligands 348 and 349 based on atropisomeric N-arylindoles and demonstrated their potency as ligands for palladium-catalyzed asymmetric allylic alkylation (up to 99% ee) (10TA711). 

Palladium-catalyzed asymmetric allylic alkylation of l,3-diphenylprop-2-enyl... 

Development of proline-derived chiral aminophosphine ligands for palladium-catalyzed asymmetric allylic alkylation 06Y628. 

Having demonstrated the potential of artificial metalloenzymes for the reduction of V-protected dehydroaminoacids, we turned our attention towards organometallic-catalyzed reactions where the enantiodiscrimination step occurs without coordination of one of the reactants to the metal centre. We anticipated that incorporation of the metal complex within a protein enviromnent may steer the enantioselection without requiring transient coordination to the metal. In this context, we selected the palladium-catalyzed asymmetric allylic alkylation, the ruthenium-catalyzed transfer hydrogenation as well as the vanadyl-catalyzed sulfoxidation reaction. Indeed, these reactions are believed to proceed without prior coordination of the soft nucleophile, the prochiral ketone or the prochiral sulfide respectively. Figure 13.5. 

Transition Metal-catalyzed Allylic Alkylation. Simple ketone enolates were found to be suitable nucleophiles for palladium-catalyzed allylic alkylations. The palladium-catalyzed asymmetric allylic alkylation of a-aryl ketones will take place in the presence of NaHMDS and allyl acetate to produce the desired a,a-disubstituted ketone derivative in high yields andee (eq 16). ... 

Oohara N, Katagiri K, Imamoto T (2003) A novel P-chirogenicphosphine ligand, (S, S)-l,2-bis-[(ferrocenyl)methylphosphino]ethane synthesis and use in ihodium-catalyzed asymmetric hydrogenation and palladium-catalyzed asymmetric allylic alkylation. Tetrahedron Asymmetry 14 2171-2175... 

MBH diene adduct 197, derived from methyl acrylate and crotonaldehyde, has been employed successfully in a palladium-catalyzed asymmetric allylic alkylation (AAA) reaction with Meldrum s acid to provide product 198 that can undergo further manipulations, as well as act as an intermediate in a one-pot tandem palladium AAA reaction. The versatility of these products for various synthetic manipulations was further illustrated by alkene metathesis to form the optically active cyclopentene 201 (Scheme 3.81). ... 

MBH diene adducts have also been employed successfully in a palladium-catalyzed asymmetric allylic alkylation reactions with various phenols in good regio- and enantioselectivity. These high enantioselectivities are even more substantial considering the ambiguity introduced by the additional double bond in the allylic system (Scheme 3.139). ... 

Franzen and coworkers described a series of indole-phos-phine-oxazoline (IndPHOX) ligands, 231-238 (Scheme 35). The power of these ligands is demonstrated by the palladium-catalyzed asymmetric allylic alkylation of 1,3-diphe-nyl-2-propenyl acetate with dimethyl malonate with 98%... 

Palladium-catalyzed asymmetric allylic alkylation of allyl dienol carbonates afforded the furanones in both high yields and high enantioselectivities. This reaction was used as the key step in the total synthesis of (-)-roccel-laric acid and (-)-nephrosteranic acid (13AGE1257). 

Asymmetric Allylic Alkylation. The first example of palladium-catalyzed asymmetric allylic alkylation (AAA) was reported three decades ago. Since this beginning intensive efforts have been done to harness the asymmetric potential of allylic alkylations. In the AAA reactions, the chiral elements can be set at the nucleophile, the electrophile, or both. 

Trost BM, Dong G (2006) New class of nucleophiles for palladium-catalyzed asymmetric allylic alkylation. Total synthesis of agelastatin A. J Am Chem Soc 128 6054-6055... 

The preparation of 2-(3 p)-[(/ra r-(2/f,5/f)-2,5-dialkylpyrrolidinyl)methyl] ferrocenyldiphenylphosphines, 41, new ferrocenylphosphinamine ligands possessing one site of planar chirality and two stereogenic centers, has been described, and their application in palladium-catalyzed asymmetric allylic alkylation reaction has been investigated. ... 

Further examples of papers are 4-ferrocenyl-l,3-oxazoline ligands in asymmetric allylation reactions ortho-silylation of 2,2, -bis(oxazolinyl)-l,l -bis(diphenylphosphino)ferrocenes in palladium-catalyzed asymmetric allylic alkylations polymer-supported ferrocenyl oxazalines for asymmetric phenyl-transfer reactions 1 -substituted... 

Scheme 41.46 Hou s palladium-catalyzed asymmetric allylic alkylation strategy for the KR of...

Lei BL, Ding CH, Yang XF, Wan XL, Hon XL. Kinetic resolution of 2,3-dihydro-2-substituted 4-quinolones by palladium-catalyzed asymmetric allylic alkylation. J. Am. Chem Soc. 2009 131(51) 18250 18251. 

Trost BM, Schroeder GM, Kristensen J. Palladium-catalyzed asymmetric allylic alkylation of a-aryl ketones. Angew. Chem. Int. Ed 2002,41(18) 3492-3495. 

Okuyama Y, Nakano H, Takahashi K, Kongo H, Kabuto C (2003) Novel and efficient chiral sulfideoxathiane ligands for palladium-catalyzed asymmetric allylic alkylation. Chem Commun 524-525... 

Dai W-M, Yeung KKY, Liu J-T, Zhang YY, Williams ID (2002) A novel class of nonbiaiyl atropisomeric P,0-ligands for palladium-catalyzed asymmetric allylic alkylation. Org Lett 4 1615-1618... 

Tollabi M, Frameiy E, Goux-Henry C, Sinou D (2003) Palladium-catalyzed asymmetric allylic alkylation using chiral glucosamine-based monophosphines. Tetrahedron Asym 14 3329-3333... 

Jiang B, Huang Z-G (2007) Chiral P,0-ligands derived from N,0-phenylene prolinols for palladium-catalyzed asymmetric allylic alkylation. Tetrahedron Lett 48 1703-1706... 

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