Tsuji-Trost reaction amines

The above-described structures are the main representatives of the family of nitrogen ligands, which cover a wide spectrum of activity and efficiency for catalytic C - C bond formations. To a lesser extent, amines or imines, associated with copper salts, and metalloporphyrins led to good catalysts for cyclo-propanation. Interestingly, sulfinylimine ligands, with the chirality provided solely by the sulfoxide moieties, have been also used as copper-chelates for the asymmetric Diels-Alder reaction. Amide derivatives (or pyridylamides) also proved their efficiency for the Tsuji-Trost reaction. 

Several Pd-catalyzed domino processes start with a Tsuji-Trost reaction, a pal-ladation of alkynes or allenes [5], a carbonylation [6], an amination [7] or a Pd(II)-cat-alyzed Wacker-type reaction [8]. A novel illustrious example of this procedure is the efficient enantioselective synthesis of vitamin E [9]. 

The Tsuji-Trost Reaction (or Trost Allylation) is the palladium-catalyzed allylation of nucleophiles such as active methylenes, enolates, amines and phenols with allylic compounds such as allyl acetates and allyl bromides. 

The catalyst is not only active in the Tsuji-Trost reaction (allylic alkylation), but also in the corresponding amination reaction. This was shown by the reaction of (ii)-l,3-diphenylprop-... 

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. 

The water soluble vitamin (+)-biotin was synthesized by M. Seki and co-workers from L-cysteine in only 11 steps using inexpensive reagents and mild reaction conditions." The key ring forming step was an intramolecular allylic amination Tsuji-Trost reaction using a nitrogen nucleophile) of a cis allylic carbonate. As expected with a soft nucleophile, the allylation took place with an overall retention of configuration. 

A wide variety of nucleophiles add to an -rf-allyl ligand. Desirable nucleophiles typically include stabilized carbanions such as CH(COOR)2 or 1° and II0 amines. Unstabilized nucleophiles such as MeMgBr or MeLi often attack the metal first and then combine with the n-allyl by reductive elimination. The Tsuji-Trost reaction, which is typified by the addition of stabilized carbanions to T 3—allyl ligands complexed to palladium followed by loss of the resulting substituted alk-ene, comprises an extremely useful method of constructing new C-C bonds, and many applications of this reaction have appeared in the literature.61 Equation 8.43 illustrates an example of a Pd-catalyzed addition of a stabilized enolate to an allyl acetate.62 The initial step in the catalytic cycle is oxidative addition of the allyl acetate to the Pd(0) complex, followed by nq1 to nq3—allyl isomerization, and then attack by the nucleophile to a terminal position of the T 3—allyl ligand. We will discuss the Tsuji-Trost reaction, especially in regard to its utility in chiral synthesis,63 more extensively in Chapter 12. 

The Pd-catalysed allylation of carbon nucleophiles with allylic compounds via Jt-aUylpaUadium complexes is called the Tsuji-Trost reaction [32]. Typically, an allyl acetate or carbonate (54) reacts with a Pd-catalyst resulting in displacement of the leaving group to generate a Jt-allylpalladium complex (55) that can undergo substitution by a nucleophile (56) (Scheme 4.14). In 1965, Tsuji reported the reaction of ti-aUylpaUadium chloride with nucleophiles such as enamines and anions of diethyl malonate and ethyl acetoacetate. A catalytic variant was soon reported thereafter in the synthesis of allylic amines [33]. In 1973, Trost described the alkylation of alkyl-substituted 7i-aUylpalladium complexes with methyl methylsulfonylacetate... 

In most of the palladium-catalysed domino processes known so far, the Mizoroki-Heck reaction - the palladium(0)-catalysed reaction of aryl halides or triflates as well as of alkenyl halides or triflates with alkenes or alkynes - has been apphed as the starting transformation accordingly to our classification (Table 8.1). It has been combined with another Mizoroki-Heck reaction [6] or a cross-coupling reaction [7], such as Suzuki, Stille or Sonogashira reactions. In other examples, a Tsuji-Trost reaction [8], a carbonylation, a pericyclic or an aldol reaction has been employed as the second step. On the other hand, cross-couphng reactions have also been used as the first step followed by, for example, a Mizoroki-Heck reaction or Tsuji-Trost reactions, palladation of alkynes or allenes [9], carbonylations [10], aminations [11] or palladium(II)-catalysedWacker-type reactions [12] were employed as the first step. A novel illustrative example of the latter procedure is the efficient enantioselective synthesis of vitamin E [13]. 

Amines are suitable nucleophiles in the Tsuji-Trost reaction, with the use of simple amines, imides, azides, sulfonamides and heterocyclic amines having been reported." In fact, one of the first examples of the catalytic version of the Tsuji-Trost reaction involved the use of aliphatic amine nucleophiles. Subsequently these important nucleophiles have been used extensively in synthesis. 

In 2006 Fukuyama published a total synthesis of racemic morphine starting from isovanillin and a cyclohexene-epoxide [16, 17]. The key features in their synthesis are (1) a construction of the ether linkage between A and C rings by Tsuji-Trost coupling, (2) an intramolecular Heck reaction to construct A-C-E tricyclic system, and (3) an intramolecular Mannich-type reaction of a ketone with an aminal to provide the pentacyclic structure of morphine in a one-step reaction by double cyclization. 

Palladium-catalyzed nucleophilic substitution of allylic substrates (Tsuji-Trost coupling) is a most important methodology in organic synthesis and therefore it is no wonder that such reactions have been developed also in aqueous systems. Carbo- and heteronucleophiles have been found to react with allylic acetates or carbonates in aqueous acetonitrile or DMSO, in water or in biphasic mixtures of the latter with butyronitrile or benzonitrile, affording the products of substitution in excellent yields (Scheme 6.19) [7-11,14,45,46], Generally, K2C03 or amines are used as additives, however in some cases the hindered strong base diazabicycloundecene (DBU) proved superior to other bases. 

When CoCl2 is used as a co-catalyst, the CDC reactions of allylic sp3 C—H and 1,3-dicarbonyl compounds smoothly afford Trost—Tsuji-type products, which are traditionally prepared from allyl halides or acetates (Equation 11.4) [14]. Moreover, when NBS is used instead of TBHP, selective C—H cleavage of tertiary aliphatic amines is possible (Equation 11.5) [15]. For benzylic C—H bonds, direct C—C bond formation can be achieved using copper perchlorate (Equation 11.6) [16]. 

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