Tsuji-Trost allylation

The Tsuji-Trost reaction is the palladium-catalyzed substitution of allylic leaving groups by carbon nucleophiles. These reactions proceed via 7i-allylpalladium intermediates. 

Name Reactions, 4th ed., DOI 10.1007/978-3-642-01053-8 256, Springer-Verlag Berlin Heidelberg 2009 

Godleski, S. A. In Comprehensive Organic Synthesis Trost, B. M. Fleming, L, eds. Vol. 4. Chapter 3.3. Pergamon Oxford, 1991. (Review). 

Moreno-Manas, M. Pleixats, R. la Advances in Heterocyclic Chemistry Kalritzky, A. R., ed. Academic Press San Diego, 1996, 66, 73. (Review). 

X = OCOR, OCO2R, OCONHRj 0P(0)(0R)2. OPh, Cl, NO2, S02Ph, NR3X, SR2X, OH 

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The inclusion of the allyl moiety in an appropriate ring system led to the formation of a new, chiral quaternary carbon center (3.13.), By the use of optically active starting material, Mori and co-workers were able to control the stereochemistry of the new chiral centre (N.B. the chirality of the first centre was also set by a palladium catalysed reaction, the Tsuji-Trost allylation).17... 

The preparation of a-lithio aldehydes, o -lithio ketones, and related compounds and their applications to organic synthesis has been reviewed.10 The Tsuji-Trost allylic alkylation with ketone enolates has been highlighted.11... 

Alkali metal enolates of ordinary ketones and aldehydes tend to fail to undergo the Tsuji-Trost allylation.37 However, it has been found that their enoxyborates and zinc enolates52 readily undergo the Pd catalysed allylation which proceeds with net retention just like the other examples of the... 

Palladium(0)-catalyzed allylation of nucleophiles (the Tsuji-Trost reaction) is a versatile synthetic method that has gained immense popularity in recent years. Rarely applied to ambident nucleophilic aromatic heterocycles before 1991, the Tsuji-Trost reaction has been extensively used in the chemistry of these compounds since 1991. Two factors have played decisive roles in this increased interest in the Pd(0)-catalyzed allylation of such heterocyclic rings one is that, unlike other alkylation procedures, the Pd(0)-catalyzed allylation can sometimes give the product of thermodynamic control when applied to ambident nucleophiles and the second is that the Tsuji-Trost allylation has become one of the standard methods for synthesizing carbanucleosides, which are important antiviral compounds (93MI1, 93MI2). Of course, the double bond of an allylic system can be modified in different directions, thus adding versatility to the Tsuji-Trost reaction. 

Allylic alcohols can serve as 7t-allyl cation precursors to act as electrophiles in Sn reactions with a tethered O-nucleophile giving rise to the formation of spiroannulated tetrahydrofurans <2000TL3411>. Michael acceptors are also suitable electrophiles for the cyclization to tetrahydrofuran rings <2003T1613>. The Tsuji-Trost allylation has found widespread application in the synthesis of carbo- and heterocyclic compounds. Allylic substitution has been employed in the stereoselective synthesis of 2-vinyl-5-substituted tetrahydrofurans <2001H(54)419>. A formal total synthesis of uvaricin makes twofold use of the Tsuji-Trost reaction in a double cyclization to bis-tetrahydrofurans (Equation 73) <20010L1953>. 

Tsuji-Trost allylation reactions offer multiple pathways to tetrahydrofuran synthesis including C-C bond-formation steps. A palladium-catalyzed sequence of allylic alkylation and Hiyama cross-coupling provides a convenient synthesis of 4-(styryl)-lactones (Scheme 67) <2006SL2231>. 

Figure 3.85 The use of the mixed NHC/phosphane ligand system in the Tsuji-Trost allylic alkylation reaction.

We conclude that the addition of phosphanes to palladium(II)-NHC complexes is advantageous with respect to reaction times, yield and completion ratio for a wide range of catalytic coupling reactions including Tsuji-Trost, allylic amination, Suzuki-Miyaura, Heck and Stille. 

TROST CHEN Decarboxylation 390 TSCHUGAEFF Olefin synthesis 391 TSUJI - TROST Allylation 392 Tsu)i 402... 

In the laboratory of B.M. Trost, the second generation asymmetric synthesis of the potent glycosidase inhibitor (-)-cyclophellitol was completed using a Tsuji-Trost allylation as the key step. The synthetic plan called for the conversion of the a-nitrosulfone allylation product to the corresponding carboxylic acid or ester. Numerous oxidative Nef reaction conditions were tested, but most of them caused extensive decomposition of the starting material or no reaction at all. Luckily, the nitrosulfone could be efficiently oxidized with dimethyidioxirane under basic conditions (TMG) to afford the desired carboxylic acid in high yield. 

The scalable total synthesis of the cytotoxic natural product (+)-FR182877 was accomplished in the laboratory of E.J. Sorensen.The key steps of the synthetis were an intramolecular Tsuji-Trost allylation to prepare the 19-membered macrocyclic pentaene followed by a double transannular DIels-Alder cycloadditlon to obtain the desired pentacyclic structure. The allylic carbonate was exposed to 10 mol% of the Pd-catalyst under high dilution conditions in THF. The new bond between Cl and Cl 9 was formed with complete diastereoselectivity and in good yield, although the configuration at Cl 9 was not determined. 

The first total synthesis of cristatic acid, a compound of considerable cytotoxic activity, was reported by A. Furstner et al." The disubstituted furan moiety was constructed by the Tsuji-Trost allylation of a vinyl epoxide intermediate by b/s(phenylsulfonyl)methane. The resulting 1,4-diol was obtained in an almost quantitative yield. 

Pd-catalyzed Tsuji-Trost allylation Pd-catalyzed allylation of carbon nucleophiles with allylic compounds via -allylpalladium complexes. 458... 

Negishi, E.-i. Palladium-catalyzed cross-coupling involving 3-hetero-substituted compounds. Palladium-catalyzed a-substitution reactions of enolates and related derivatives other than the Tsuji-Trost allylation reaction. Handbook of Organopalladium Chemistry for Organic Synthesis 2002, 1, 693-719. 

For a recent study of memory effects in Tsuji-Trost allylation reactions, see P. Fristrup, T. Jensen, J. Hoppe, and P.-O. Norrby, Chem. Eur. J., 2006,12, 5352 for some experimental... 

The enantioselectivity associated with quaternary allylation is connected with scenario 5 above (one of the five points associated in the catalytic cycles shown by Schemes 12.10a and b where chirality could be induced), which is where enantioselection of one of two faces of the nucleophile (the enolate ion) occurs. Theoretical studies of the transformation using the PHOX ligand have shown support for an inner sphere mechanism, where nucleophilic attack of the enolate onto the rf-allyl ligand occurs from the Pd-bound enolate and not from an external nucleophile.74 These studies have not been able to definitively determine the step that defines the enantioselectivity of the reaction, and it is not clear how these results would carry over to reactions involving the Trost ligands. At this time, selection of which ligand one should use not only to induce enantioselectivity but also to predict the sense of absolute configuration of any asymmetric Tsuji-Trost allylation is mostly based on empirical results. Work continues on this... 

Use of Tsuji-Trost Allylation Reaction in Generating a Key Quaternary Center during Synthesis of (-i-)-Dichroanone... 

The variety of carbon fragments that can join and the general tolerance of the reaction conditions to functional groups already present on these fragments lead to countless possibilities for rapid construction of complex molecules, especially biologically active compounds. One key difference between cross-coupling reactions and the Tsuji-Trost allylation or Heck olefination is the occurrence of a transmetalation step during the catalytic cycle. 

The comparison of intramolecular carbopalladation reactions of allenes and alkenes outlined in Schemes 9-5 and 9-6 illustrates that not every transition metal catalyzed ring closure necessarily involves a template effect. Others, however, clearly benefit from it. A prototype example is the palladium catalyzed cycloisomerization of alkenyl epoxides carrying distal pre-nucleophiles [38, 39], representing one variant of the famous Tsuji-Trost allylation [40]. 

The Tsuji-Trost allylation of enolates can be viewed as a variant of Pd-catalyzed cross-coupling involving aUylic electrophiles (Sects, ni.2.9 and III.2.10). In recognition of the widely accepted mechanism involving a nucleophilic attack by enolates at the TT-allyl ligand of an allylpalladium derivative on the side opposite to Pd, however, it is discussed separately in Part V together with the Wacker and related reactions, which are... 

III.2.14.1 Palladium-Catalyzed of-Substitution Reactions of Enolates and Related Derivatives Other than the Tsuji-Trost Allylation Reaction... 

In this section, attention is focused on the Pd-catalyzed a-substitution reactions of enolates and related derivatives represented by Method I in Scheme 1, other than Tsuji-Trost allylation and propargylation. Additionally, its charge-affinity inverted version represented by Method II in Scheme 1 is also discussed. In general, it is advisable to consider simultaneously various other alternatives including those shown in Scheme 1, especially Method III. Indeed, Method III discussed in the following section provides the currently most... 

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