Hetero-Diels-Alder reactions triflate

Similar aza-Diels-Alder reactions of Danishefsky s diene with imines or aldehydes and amines in water took place smoothly under neutral conditions in the presence of a catalytic amount of an alkaline salt such as sodium triflate or sodium tetraphenylborate to afford dihydro-4-pyridones in high yields (Eq. 12.49).117 Antibodies have also been found to catalyze hetero-Diels-Alder reactions.118... 

The hetero Diels-Alder reactions discussed thus far use 2-10 mol% of catalyst. Jorgensen s group44b found that the reaction could be carried out even at very low catalyst loading. The catalyst can conveniently be prepared in situ by mixing the chiral ligand 83 and copper triflate in the reaction system. Scheme 5-35 shows that product 112 can be obtained with good yield and high enan-... 

Although several Lewis acids are known to catalyze the hetero-Diels-Alder reaction involving imino-dienes or imino-dienophiles (aza-Diels-Alder reaction), a large amount of the catalyst is often necessary. Bi(0Tf)3-xH20 showed higher activity than lanthanide triflates in catalyzing the reactions of imines with Danishefsky s diene (Scheme 15) [72]. 

It has been shown that complete selectivity for the hetero-Diels-Alder cycloadduct 109 (100% endo, 60% ee) can be achieved in the hetero-Diels-Alder reaction of 1,3-cyclohexadiene 108 and ethyl glyoxylate 99 using ent-6 and copper(II) triflate derived catalyst complex. Another interesting reaction introduced by Jprgensen and co-workers was the reaction between 1,3-cyclohexadiene 108 and diethyl ketomalonate 110 to form cycloadduct 111 in 76% yield with an ee of 84% (Fig. 9.35b, p. 558). ... 

Ghosez and co-workers also presented a hetero-Diels-Alder reaction using a hetero-atom-containing diene 121 and the oxazolidinone 80a in the presence of bu-box 3 complexed with copper(II) triflate to afford the cycloadduct 122 in 80% yield (>99 1 exo/endo, 95% ee) as shown in Figure 9.38Z . ... 

The choice of solvent has had little, if any, influence on the majority of Diels-Alder reactions.210,211 Although the addition of a Lewis acid might be expected to show more solvent dependence, generally there appears to be little effect on asymmetric induction.118129 However, a dramatic effect of solvent polarity has been observed for chiral metallocene triflate complexes.212 The use of polar solvents, such as nitromethane and nitropropane, leads to a significant improvement in the catalytic properties of a copper Lewis acid complex in the hetero Diels-Alder reaction of glyoxylate esters with dienes.213... 

For a recent study concerning lanthanide triflates in hetero-Diels-Alder reactions of 2-azabutadienes see Makioka Y, Shindo T, Taniguchi Y, Takaki K, Fujiwara Y (1995) Synthesis 801... 

The first catalytic, highly enantio selective hetero Diels-Alder reactions of thiabutadienes with an acyloxazolidinone dienophile using homochiral copper and nickel triflate and perchlorate bis(oxazoline) and bis(imine)complex catalysts to generate dihydrothiopyrans were reported by Saito et al. [155]. 

The enantioselective total synthesis of the Securienega alkaloid (-)-phyllanthine by S.M. Weinreb et al. involved a stereoselective Yb(OTf)3-promoted hetero Diels-Alder reaction between a cyclic imine dienophile and Danishefsky s diene This was the first example of using an unactivated cyclic imine in this type of cycloaddition. Commonly used Lewis acid catalysts (e.g., SnCb, TiCU, etc.) produced only low yields of the desired cycloadduct. However, it was discovered that ytterbium triflate catalyzed the cycloaddition and afforded the product in 84% yield. Later they also found that the cyclization could occur at high pressure and in the absence of the catalyst, although a slightly lower yield (71%) of the product was obtained. 

Chiral lanthanide bistrifylamides were prepared through the reaction of lan-thanide(III) triflates and chiral bistrifylamides, which are deprotonated with 2 equivalents of sodium hydride in THF for 1 h. Dichloromethane or toluene was introduced, after evaporation of THF, to the residual complex. The resultant suspension of the lanthanide complex was then used for the hetero-Diels-Alder reaction (Scheme 16). 

Yadav, J.S., Reddy, B.V.S., Gayathri, K.U. and Prasad, A.R. (2002) Scandium triflate immobilized in ionic liquids A novel and recyclable catalytic system for hetero-Diels-Alder reactions. Synthesis-Stuttgart, 17, 2537-2541. 

Additives that can be added to aqueous reactions include Lewis acids, which have roles as catalysts in organic transformations, mainly in Diels-Alder reactions [24]. A number of Lewis acids which can be used in water have been described, such as nitrates, for example, Cu(N03)2 and Zn2 +, Ni2 +, Co2+ analogs [25], lanthanide triflates, Ln(OTf)3 [26], and others, including indium trichloride [27]. Increased yields and product selectivities have been observed in several systems. A typical example is the three-component hetero-Diels-Alder reaction catalyzed by lanthanide triflate (Equation 4.14). Lanthanide triflates were used in the pH range 5-7, and when no Ln (OTf)3 was added, the product was isolated in only 4% yield however, with added lanthanide catalyst the yield was increased to 64% [28]. 

Hetero-Diels-Alder reactions have been used in the construction of amino-sugars, asymmetry being induced by the use of either a chiral Lewis acid catalyst or a chiral auxiliary. Thus, the 3-amino-hexuronic acid derivatives 61 were obtained with high de and ee using a copper(II) triflate catalyst with a chiral bisoxazoline ligand. 4-Amino-4-deoxy-D-erythrose and 4-amino-4,5-dideoxy-L-lyxose (63), the latter a potent inhibitor of a-L-fucosidase, were obtained from the D-pyroglutamic add-containing diene 62 (Scheme 19). ... 

In addition to metal-based catalysts, organocatalysts are also selective promoters of asymmetric Diels-Alder reactions. Several groups reported the use of cinchona alkaloid catalysts in standard Diels-Alder reactions. Deng combined 2-pyrones with a,P unsaturated ketones, while Bernard and Ricci focused on the reactions of vinylindoles with quinones and maleimides. Lectka reported enantioselective inverse electron demand hetero Diels-Alder reactions of ketene enolates and o-benzoquininone diimides catalyzed by a combination of benzoylquinidine and zinc triflate. For example, subjecting diimide 51 to the standard reaction conditions yields cycloadduct 52 as a single stereoisomer, which can be easily converted to... 

Asymmetric Hetero-Diels-Alder Reactions. By using stoichiometric amounts of the bis(oxazoline)-copper(II) triflate system as catalyst, asymmetric hetero-Diels-Alder (HDA) cycloaddition reactions were performed with cyclic and acyclic 1,3-dienes. The reported enantioselectivity (70-98% ee) and... 

Diels-Alder reactions constitute one of the most important methodologies for the constructuction of a cyclic molecular framework. Lanthanide Lewis acid catalyzed Diels-Alder reaction was pioneered by Danishefsky et al., who revealed that NMR shift reagent Eu(hfc)3 served as chiral catalyst in hetero Diels-Alder reaction of silyloxydiene and aldehydes [32]. Later, although Yb(OTf)3 was first introduced for Diels-Alder reactions as an effective catalyst among lanthanide triflates, scandium triflates (Sc(OTf)3), classified as rare earth metal triflate, has gained popularity as a superior catalyst for Diels-Alder reactions [11, 33]. This section highlights several examples of the reactions where lanthanide triflates displayed preferable performance over scandium triflates. 

The catalytic enantioselective hetero-Diels-Alder reactions between ketomalonate and activated and non-activated conjugated dienes yield cycloadducts which can be converted into chiral COa-synthons. The intramolecular Diels-Alder reaction of sulfolene masked diene synthon (169) yield 5-carbomethoxy yohimbine systems (170) and (171) with ejco-stereochemistry (Scheme 65). Trimethylsilyl triflate catalyses... 

The Frost group has demonstrated the use of indium(III) triflate as a catalyst for hetero Diels-Alder reactions. In the presence of just 0.5 mol % of catalyst, the imino Diels-Alder reaction of an imine and Danishefsky s diene provides the product in excellent yields (eq 16). A three-corrponent coupling of an aldehyde, amine, and diene was also reported. 

In 2006, Lectka and coworkers reported an asymmetric inverse electron demand hetero-Diels-Alder reaction (HDAR) of acyl chlorides (Bekele et al. 2006 Wolfer et al. 2006) and o-benzoquinone diimides to deliver chiral quinoxalinones (Abraham et al. 2006). In spite of perfect ee values observed by the catalysis of Lewis bases derived from cinchona alkaloids, the reaction conditions were somewhat harsh and metal triflates had to be used as co-catalysts to activate the electrophilic o-benzoquinone diimides (Abraham et al. 2006 Pauli et al. 2(X)8). 

Another example of the use of Lewis acids in organic reactions in water is the lan-thanide(III) triflate catalysed aza-Diels-Alder reaction, exemplified in Scheme 14. In this reaction the hetero-dienophile is formed in situ from a primary ammonium hydrochloride and a carbonyl compound followed by the actual Diels-Alder reaction288,289. This type of reaction proceeds readily in aqueous media290-296, and a dramatic increase in the yield upon addition of lanthanide triflates was observed288,289. The exact role of the catalyst, however, is not entirely clear. Although it was suggested that the catalyst binds to the dienophile, other mechanisms, such as simple proton catalysis, are also plausible. Moreover, these reactions are further complicated since they are often heterogeneous. 

The 2-ethynyldihydropyran 6 results from the asymmetric Cr-catalysed hetero Diels-Alder (hDA) reaction of l-benzyloxybuta-l,3-diene with alkynal 5 and subsequent desilylation (Scheme 3) <01AG(E)3667>. A triflate-catalysed enantioselective construction of a dihydropyran from a chiral crotylsilane and an alkynal features in a synthesis of the C19-C28 fragment of the phorboxazole system <01OL1693>-... 

From Achiral Non-carbohydrates. — 3-Deoxy-3-guanidino-D-threose 48 equilibrates with 49. a transition state inhibitor for galactosidase. It was synthesized as shown in Scheme 12 from epoxide 47, which was obtained by porcine pancreatic lipase catalysed enantioselective esterification of the racemic epoxy-alcohol precursor. 6-Deoxy-L-talonolactone 50 was synthesized by an asymmetric aldol condensation - dihydroxylation sequence (Vol.24, p.lS2) in improved diastereoselectivity and was converted into 2-acetamido-2,6-dideoxy-L-fucose (shown as its furanose isomer 51 in Scheme 13), 3-acetamido-3,6Hlideoxy-L-idose and 5-acetamido-S,6-dideoxy-D-allose by S 2 displacements of triflate with azide ion. 4-Amino-4-deoxy-DL-erthrose 53 was obtained from the hetero-Diels-Alder adduct 52 by a sequence of reactions including cis-dihydroxylation (OSO4, NMNO) of the alkene moiety (Scheme 14). The synthesis of a racemic branched-chain lactam is covered in Chapter 16. 

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