Allyl enol carbonates, Tsuji

Enol carbonates react with alkylating agents in the presence of a palladium catalyst. The decarboxylative alkylation of allyl enol carbonates to the corresponding aUylcyclohexanone derivatives is known as the Tsuji alkylation. An asymmetric version of this reaction has been reported. The same reaction can be done using enolate anion and aUylic acetates with a palladium catalyst. ... 

Palladium-Catalyzed Asymmetric Tsuji Allylation of Allyl Enol Carbonates... 

Nucleophiles used in the seminal papers by Tsuji and co-workers were mostly stabilized carbon nucleophiles, and the method found an early synthetic application in a preparation of steroids." It soon became evident that many other types of nucleophiles could be used. In particular, hydride ion equivalents led to l-olefinsf ° " (see Sect. V.2.3.1), Silyl and stannyl enolates of simple ketones and aldehydes and esters can be aUylated, as well as allyl enol carbonates (see Sect. V.2.1.4), This is an indirect a-aUylation of ketones, aldehydes, and esters. Enol derivatives can take another reaction course under Pd(0) catalysis (Scheme 2). Thus, oxidation to a,/3-unsaturated carbonyl compounds ensues if reactions are performed in acetonitrile under precise sources of catalyst precursor. "" "" A full discussion on the dichotomy of allylation-oxidation has been published, as well as a comparison of the usefulness of several transition metals as catalysts in allylation of nucleophiles. ... 

The use of palladium(II) 7i-allyl complexes in organic chemistry has a rich history. These complexes were the first examples of a C-M bond to be used as an electrophile [1-3]. At the dawn of the era of asymmetric catalysis, the use of chiral phosphines in palladium-catalyzed allylic alkylation reactions provided key early successes in asymmetric C-C bond formation that were an important validation of the usefulness of the field [4]. No researchers were more important to these innovations than Prof. B.M. Trost and Prof. J. Tsuji [5-10]. While most of the early discoveries in this field provided access to tertiary (3°) stereocenters formed on a prochiral electrophile [Eq. (1)] (Scheme 1), our interest focused on making quaternary (4°) stereocenters on prochiral enolates [Eq. (2)]. Recently, we have described decarboxylative asymmetric allylic alkylation reactions involving prochiral enolates that provide access to enantioenriched ot-quatemary carbonyl compounds [11-13]. We found that a range of substrates (e.g., allyl enol carbonates,... 

To overcome the limitation of the high stability of the aluminum enolates, the oxygen atom has been transformed to silyl enol ethers, enol acetates, and allyl enol carbonates. Silyl enol ethers and enol acetates are precursors to lithium enolates. Enol acetates and allyl enol carbonates are precursors of cx-allylated adducts via the Tsuji-Trost rearrangement [75-77]. The silylation of aluminum enolates using TMSOTf is well established [78], although in some cases the isolation is difficult [33]. Silyl enol ethers allow further modification to be performed as they behave as lithium enolates (Scheme 15). A recent application can be found in the silylation of the conjugate addition adduct (/ )-((3-(but-3-en-l-yl)-3-methylcyclopent-l-en-l-yl)oxy)triethylsilane which allows aldol condensation to form an intermediate in the synthesis of Clavirolide C [79], a diterpene with a trans-bicyclo[9.3.0] tetradecane structure (Scheme 16) [80]. 

Allyl Enol Carbonates In 2004, the Stoltz group introduced the first enantioselective Tsuji allylation from allyl enol carbonate substrates (Scheme 7.22)." " They found that the use of t-Bu-PHOX 132 ligand provided both high enan-tioselectivity and yield, generating 2-methyl-2-allylcyclo-hexanone in 90% yield and 89% ee. Expansion of the scope allowed for incorporation of branched allyl components as well as for a variety of substituents at the 2-position... 

Silyl Enol Ethers A disadvantage of the aforementioned enantioselective Tsuji allylations was that they were performed in an intramolecular fashion, requiring the need to synthesize the allyl enol carbonate starting materials. Although their synthesis is not overly cumbersome, the... 

Tsuji J, Minami I, Shimizu I. Palladium-catalyzed allylation of ketones and aldehydes via allyl enol carbonates. Tetrahedron Lett. 1983 24 1793-1796. 

Our first hurdle was to determine if this selectivity would be maintained in the presence of steric bulk disposed p to the ketone. We synthesized model enol carbonate 4 and were encouraged to find that it selectively produced the desired a-quatemary ketone. Ultimately, difficulties in preparing an appropriate methyl ketoie prevented us from executing this strategy, but the selectivity and utility of Tsuji s allylation reaction for making quaternary stereocenters left a lasting impression. 

Ketone and ester enolates have historically proven problematic as nucleophiles for the transition metal-catalyzed allylic alkylation reaction, which can be attributed, at least in part, to their less stabilized and more basic nature. In Hght of these limitations, Tsuji demonstrated the first rhodium-catalyzed allylic alkylation reaction using the trimethly-silyl enol ether derived from cyclohexanone, albeit in modest yield (Eq. 4) [9]. Matsuda and co-workers also examined rhodium-catalyzed allylic alkylation, using trimethylsilyl enol ethers with a wide range of aUyhc carbonates [22]. However, this study was problematic as exemplified by the poor regio- and diastereocontrol, which clearly delineates the limitations in terms of the synthetic utihty of this particular reaction. 

With ample supplies of 38 provided through this protocol, the Sorensen group could next attempt to attach the atoms needed to prepare 37, the projected intermediate for a second reaction based on 7T-allyl palladium complexes (a Tsuji—Trost reaction) that would hopefully lead to the 19-membered macrocycle 36. In essence, this requirement boiled down to only two key synthetic objectives generating a ketoester moiety from the Weinreb amide, and converting the allylic TES-protected alcohol function at Cl into a methyl carbonate. Neither of these tasks ultimately proved to be overly challenging to carry out, with the first accomplished by treating 38 with excess quantities of the lithium enolate of t-butyl acetate to provide 54, and the second requiring three rela-... 

Although it is mechanistically different from the Tsuji-Trost allylation, indirect allyla-tions of ketones, aldehydes, and esters via their enolates are briefly summarized here. Related reactions are treated in Sect V.2.1.4. Pd-catalyzed allylation of aldehydes, ketones, and esters with aUyhc carbonates is possible via the Tr-allylpaUadium enolates of these carbonyl compounds. Tr-AUylpalladium enolates can be generated by the treatment of silyl and stannyl enol ethers of carbonyl compounds with allyl carbonates, and the allylated products are obtained by the reductive elimination of the Tr-allylpalladium enolates. 

Trost and Runge announced in 1981 the use of simple allyl carbonates and described even earlier the Pd(0)-catalyzed rearrangement of allyl ethers of enolic /3-ketoesters into the isomeric a-allyl-/S-ketoesters (Scheme 5). Allyl ethers of enolic /3-ketoesters are vinylogous of allyl carbonates In 1980 Tsuji and co-workers described a similar rearrangement,declaring that the palladium-catalyzed rearrangement of a similar cyclic ether has been presented in a lecture by B.M. Trost at the 1st Intern. Kyoto Conf. Org. Chem., Dec., 6,1979. ... 

A complementary functional cyclopropane assembly relies on the utilization of the Tsuji-Trost reaction [101], A highly enantio and diastereoselective cou-pling/cyclopropanation sequence of acyclic amides 85 with allyl carbonates 86 is illustrated in Scheme 5.30 [102], In this reaction, a scarcely described addition of the nucleophilic enolate intermediate onto the central carbon of the i-allyl palladium is involved, which affords the corresponding cyclopropane. 

The Tsuji-Trost reaction is the palladinum-catalyzed substitution of allylic leaving groups by carbon nucleophiles. The nucleophile can be carbon-, nitrogen-, or oxygen- based compounds such as alcohols, enolates, phenols, and enamines, and the leaving group can be a halide or an acetate. This emerged as a powerful procedure for the formation of C—C, C—O and C—N bonds. The reaction, also known as Trost allylation or allylic alkylation, was named after Jiro Tsuij, who first reported the method in 1965 [42], and Barry Trost, who introduced an asymmetric version in 1973 [43]. 

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