Resolutions allyl acetates

Kinetic resolution of racemic allylic acetates has been accomplished via asymmetric dihydroxylation (p. 1051), and 2-oxoimidazolidine-4-carboxy-lates have been developed as new chiral auxiliaries for the kinetic resolution of amines. Reactions catalyzed by enzymes can be utilized for this kind of resolution. ... 

Catalysts lacking phosphorus ligands have also been used as catalysts for allylic substitutions. [lr(COD)Cl]2 itself, which contains a 7i-accepting diolefin ligand, catalyzes the alkylation of allylic acetates, but the formation of branched products was only favored when the substitution reaction was performed with branched allylic esters. Takemoto and coworkers later reported the etherification of branched allylic acetates and carbonates with oximes catalyzed by [lr(COD)Cl]2 without added ligand [47]. Finally, as discussed in Sect. 6, Carreira reported kinetic resolutions of branched allylic carbonates from reactions of phenol catalyzed by the combination of [lr(COE)2Cl]2 and a chiral diene ligand [48]. 

At the same time and in the years to follow, several other groups reported the observation of high selectivities in the Pd-catalyzed resolution of racemic substrates [6]. The kinetic resolution depicted in Scheme 2.1.4.2 gives access to both the enantio-enriched allylic acetate and sulfone. Because of the many applications chiral allylic alcohols and allylic sulphur derivatives have found in the synthesis... 

The kinetic resolution of the racemic allylic acetates rac-3ab, rac-ldb, rac-lab, and rac-lbb with thiocarboxylate ions and BPA were investigated in more detail (Scheme 2.1.4.22). The acetates were selected instead of the corresponding carbonates in order to avoid the competing formation of the corresponding allylic alcohols (vide supra). All reactions were carried out in CH2CI2/H2O (9 1) using 2 mol% of Pd(0)/L and 8 mol% of BPA. Termination of the reaction of the pen-tenyl acetate rac-3ab with KSAc at 35% conversion showed the operation of highly selective kinetic resolution (entry 4). However, 50% conversion of the substrate could be achieved neither at room nor at reflux temperature. This is in contrast to the reactivity of carbonate roc-3aa (cf. Table 2.1.4.14, entry 1) and perhaps reflects the lower reactivity of allylic acetates in Pd-catalyzed alkylation. This... 

Scheme 2.1.4.22 Pd(0)/BPA-catalyzed kinetic resolution of allylic acetates with KSAc and KSBz.

The Pd-catalyzed rearrangements most probably follow an ionization-substitution pathway with the intermediate formation of a jc-allyl-Pd complex. The Pd-catalyzed allylic alkylation is generally accompanied by a highly selective kinetic and synthetically useful resolution of the racemic allylic acetates and carbonates. 

J. Y. Jung, and M. J. Kim, Dynamic kinetic resolution of acyclic allylic acetates using lipase and palladium, J. Org. Chem. 1999, 64(22), 8423-8424. 

The use of a metal catalyst, such as palladium, also provides for some asymmetric induction when an allylic system is treated with a stabilized anion (Scheme 22.13)82-103 or with other nucleophiles.82,87,104-111 This approach also allows for the kinetic resolution of allyl acetates.104,112... 

Lipases have also been combined with palladium catalysts to provide the dynamic aspect of the kinetic resolution.30 In the example below the unreacted allyl acetate (5)-49 is racemised. The formation and reactions of Pd-allyl cations are discussed in chapter 18. 

The first example of the use of enzyme and metal combinations to provide a dynamic resolution procedure was reported by Allen and Williams in 1996[18. In this case, a palladium (II) catalyst was employed that was able to racemize the allylic acetate substrate, but did not erode the enantioselectivity of the product allylic alcohol (Fig. 9-11). For example, a cyclic acetate was shown to undergo a simple kinetic resolution, affording enantiomerically enriched starting material and product at approximately 50 % conversion. However, performing the reaction in the presence of a palladium (II) catalyst facilitated a dynamic resolution by continuously racemiz-ing the starting material as the reaction progressed. 

Similar methodology was applied to an acyclic allylic acetate by the group of Kim, who used Pd(0) catalysts119. Acyclic allylic acetates are easier substrates for palladium-catalyzed racemization, and these workers were able to effect a dynamic resolution strategy within a more acceptable time scale (Fig. 9-11). The in situ racemization with palladium catalysts is limited in scope, since allylic acetates are required as substrates. In addition, not all allylic acetates are expected to undergo facile racemization 20. ... 

Another ruthenium catalyst was used for the dynamic kinetic resolution of allylic alcohols [reaction (24)] by acylation yielding allylic acetates. Again a redox process should be responsible for the racemization. 

In his pioneering contributions Moiseev has shown that giant cationic palladium clusters , e.g. Pd56iL6o(OAc)i8o (L = phenanthroline, bipyridine), characterized by use of high-resolution TEM, SAXS, EXAFS, IR and magnetic susceptibility data, catalyze, under mild conditions (293 363 K, 1 bar), the oxidative acetoxylation of ethylene into vinyl acetate, propylene into allyl acetate, and toluene into benzyl acetate. The oxidation of primary aliphatic alcohols to esters, and the conversion of aldehydes into acetals were also studied. ... 

Finally, the use of stoichiometric amounts of transition metal complexes can play an important role in the synthesis of functionalized piperidines. <01H14.39> Liebeskind and coworkers have developed a chiral transition metal complex and have used it in the synthesis of (-)-indolizidine 209B <01JA12477>. A lipase mediated allylic alcohol resolution provides access to both antipodes of enantiomerically pure allyl acetates (115) which can be used to form an ri -allyl molybdenum complex (116), Hydride abstraction followed by methoxide quench yields a reactive species 117 which may be further functionalized through reactions with Grignard reagents. The eventual products 119 arc 2,3,6-trisubstituted piperidines in enantiomerically pure form. 

The first example involves the kinetic resolution of allylic acetates. In the asymmetric synthesis of (+)-cyclophellitol, the two enantiomers of the tetraacetate in Figure 14.26 were resolved by substitution of a pivalate group for one acetate. The palladium catalyst bearing the (R,R)-L ligand shown reacted faster with the (R)-allylic acetate. ... 

Kinetic resolutions of allylic esters have also been conducted. As noted in Chapter 14, in most cases, catalysts that are selective for kinetic resolution of substrates containing one type of functional group are also selective for reactions of meso substrates and vice versa.The enantioselective reaction of one acetate of a meso substrate involves similar stereochemical recognition to reaction of two enantiomers of a racemic mixture of allylic esters. In one illustrative example, an allylic acetate underwent reaction with a pivalate nucleophile to form the allylic pivalate product, which is less reactive than the starting compound (Equation 20.54). Reaction of one enantiomer of the racemic allylic acetate occurs preferentially, and the pivalate product is formed enantioselec-tively. The product of the resolution in Equation 20.54 was carried forward to form (+)-cyclophellitol. 

Allyl acetates 1/ent-l that possess identical R groups undergo aUyUc substitution via an achiral intermediate 2. Both enantiomers of starting material proceed via the same intermediate. In the absence of any controlling influence, approach of the nucleophile via pathways a and b is equally likely, and a racemic product 3/ent-3 will be formed (Scheme 1). However, the opportunity for an asymmetric catalytic reaction exists if the reaction can be channeled through one pathway selectively. Overall, the process represents a dynamic resolution, since a racemic starting material is converted into an enan-tiomericaUy emiched product. 

When a racemic allylic substrate is employed in an enantioselective substitution reaction, one of the two substrate enantiomers may react more quickly than the other. This effect is a kinetic resolution and has been noted reasonably often in enantioselective allylic substitution reactions. Several studies on kinetic resolution have been reported, - and a few highlight reactions are noted in Scheme 45. These include recovery of unreacted cy-clohexenyl acetate 92, as well as the tetraacetate 225. Kinetic resolution has also been observed in allylic snbstitution using a snlfinate nucleophile (Li02STlu) with allyl acetate... 

Optically active barbiturates important in pharmacy, are obtained by classical synthesis and resolution procedures [14]. A new approach to the synthesis of optically active barbiturates is enantioselective catalysis with Pd complexes. An example is shown in Scheme 10 on the right side. The synthesis of the enantiomers of a N-methyl barbiturate containing a quaternary asymmetric carbon atom is achieved by allylation of the corresponding precursor with allyl acetate. Pd/triphenylphosphine complexes are efficient catalysts for this reaction which give a racemic mixture of the product. The reaction proceeds via a jt-allyl complex of Pd as an intermediate (Scheme 10, left side). This 7t-allyl complex is attacked by the nucleophile, the anion of N-... 

In an extension of previous work, it has been found that Pd(0)-catalysed intramolecular cyclization of allylic acetates (21) can be used to prepare the chrysanthemic acid analogues (22). The potentially useful cw-cyclopropane (23) can be simply obtained by base-induced addition of cyanoacetate to ethyl 2-bromo-3,3-dimethylacrylate followed by decarboxylation oddly, a similar reaction using malonate fails to give a cyclopropane. Optically pure dichloro cw-chrysanthemic acid (26) has been obtained by a Favorskii rearrangement of the chiral cyclobutanone (25) prepared from the keten (24) by sequential [2 + 2]cycloaddition, cine-rearrangement, and resolution (Scheme 3). ... 

The allylation of cyclic acetates such as cyclopentenyl or cyclo-hexenyl and cycloheptenyl derivatives also has been widely studied. For exart ile, the allyl palladium chloride dimer (1) is a useful catalyst precursor in the kinetic resolution of 2-cyclohexenyl acetate using Trost s chiral ligands pockets in conjunction to the planar chirality of ferrocene (eq 46). 1 The conversion was stopped at 54%, which allowed high enantiomeric excess for both the alkylated derivative and the chiral allylic acetate. 

Other reports include the kinetic resolution of racemic allylic acetates in an asymmetric alkylation reaction catalysed by chiral ferrocenylphosphine palladium complexes and the use of the ferrocenyl group in peptide chemistry. ... 

SCHEME 64 Kinetic resolution of allyl acetate giving rise to enantiomerically pure a-allyl lactone. 

B. Mao, Y. Ji, M. Fananas-Mastral, G. CaroH, A. Meetsma, B.L. Feringa, Highly enantioselective synthesis of 3-Substituted y-butenolides by palladivun-catalyzed kinetic resolution of unsymmetrical allyl acetates, Angew. Chem. Int. Ed. 51 (2012) 3168-3173. 

Scheme 5.28 Kinetic resolution in the reaction of racemic allylic acetate 86 with 2-trimethylsiloxyfuran, mediated by palladium with the chiral ligand (fl,/ )-14.

Resolution (enantiomers), 307-309 Resonance, 43-47 acetate ion and, 43 acetone anion and. 45 acyl cations and, 558 allylic carbocations and, 488-489 allylic radical and, 341 arylamines and, 924 benzene and, 44. 521 benzylic carbocation and, 377 benzylic radical and, 578 carbonate ion and. 47 carboxylate ions and, 756-757 enolate ions and, 850 naphthalene and, 532 pentadienyl radical and. 48 phenoxide ions and, 605-606 Resonance effect, 562 Resonance forms, 43... 

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