Asymmetric ionic Diels-Alder reaction

Scheme 8 Model asymmetric aza Diels-Alder reaction in the presence of chiral ionic liquids...

Asymmetric aza-Diels-Alder reaction of chiral imines with Danishefsky s diene in chiral ionic liquids have been reported [89]. These reactions occur at room temperature under green chemistry conditions without using Lewis acid catalyst and organic solvent. For example, the reaction of Danishefsky s diene 76 with imine 104 in the presence of chiral ionic liquid (EL) 105, gives pyridone derivative in moderate diastereoselectivity [89]. In the TS, the chiral liquid 105 binds the diene... 

In recent screening for the best catalyst for an asymmetric Diels-Alder reaction between fumarate and cyclopentadiene, BiCls gave poor stereoselectivity (Equation 23) [40b]. The same result was obtained when BiCla was tested in catalysis of asymmetric ionic Diels-Alder for the synthesis of cis-decalins [41]. 

Since the first publication, amine-catalyzed Diels-Alder reactions of a,/ -unsaturated aldehydes have been investigated in much detail [15, 26-33]. Catalyst immobilization studies on solid support [26, 27], as well as in ionic liquids [29], have shown advantages for amine recycling, while partially maintaining good levels of asymmetric induction [34]. The use of this reaction in total synthesis has allowed the rapid preparation of (+)-hapalindole Q, a tricyclic alkaloid natural product containing four contiguous stereocenters (Scheme 3.2) [28]. 

Some attempts have been made towards asymmetric Diels-Alder reactions by using chiral ionic liquids. However, neither with a chiral cation, viz. A r.A r-di(2. S -2 -mcthylbutaiic)imida/olium.1116 nor a chiral anion, viz. /.-lactate, 117 could any significant chiral induction be observed. However, substantial chiral induction was achieved with a chiral organic catalyst immobilised in either [C4Ciim][PF6] or [C4Ciim][SbF6], as shown in Scheme... 

In the reaction between cyclohexadiene and acrylate, ees as high as 93% could be observed. An ionic liquid composed of a structurally related chiral cation is thus likely to promote asymmetric Diels-Alder reactions. 

It is noted that the Diels-Alder reaction has been done with supercritical and with supercritical water as solvents. Diels-Alder reactions on solid supports have also been reported, and zeolites have been used in conjunction with catalytic agents. ° Alumina has been used to promote Diels-Alder reactions. ° Diels-Alder reactions can be done in ionic liquids,including asymmetric Diels-Alder reactions. ... 

Oh and Meracz were the first to report asymmetric Diels-Alder reaction in ionic liquids [43]. It has also been shown that Diels-Alder reactions in ionic liquids give unusually high stereoselectivities at room temperature as compared to those in conventional organic solvents, where a low temperature was required to achieve good stereoselectivities. For example, the Diels-Alder reaction of cyclopentadiene and dienophile 25 with Cu(ll)-bisoxazoline complex 24 as catalyst in [dbim][BF4] showed a higher endoselectivity (endo j exo = 93/7) and regioselectivity (26/27 = 96/4) than in CHjCb (endojexo = 79/21, 26/27 = 76/24) (Scheme 7.11). 

Table 7.7 Asymmetric Diels-Alder reaction between cyclopentadiene and dienophile 25 in ionic liquids using 5-28, 5-29 and (S)-30 as catalysts.

Quite recently, palladium-phosphinooxazohdine catalysts have been used for asymmetric Diels-Alder reactions in ionic liquids [45]. By screening various counterions of the Pd catalysts and ionic liquids, a combination of cationic Pd-POZ catalyst 31c with ShF counterion and [bmim][BF4] as the ionic liquid was found to be the most effective. The Diels-Alder reaction of cyclopentadiene with dienophile 32 using 31c as a catalyst provided DA adduct 33 with high chemical and optical yields. The catalyst 31c immobilized in [bmimJfBFJ was successfully recycled eight times to give 33 in 89-99% yields and 88-99% ee-values (Scheme 7.12). 

Catalytic asymmetric Diels-Alder reactions in ionic liquids, using an air- and moisture-stable chiral BlNOL-indium complex prepared from ( S)-BINOL and InClj, have also reported [46]. The reactions of various dienes with 2-methacrolein or 2-bromoacrolein proceeded in an ionic hquid with good yields and excellent enantioselectivities (up to 98% ee). The chiral In(lll) catalyst immobilized in ionic liquid [hmim][PF 5] could be reused seven times without any significant loss in catalytic activity (Scheme 7.13). 

Asymmetric Diels-Alder reactions in ionic hquids have been conducted using the privileged MacMillian s catalyst imidazohdin-4-one 51 [97]. The Diels-Alder reachons between cyclohexadiene and acrolein were carried out using 5 mol% of... 

Table 7.15 Asymmetric Diels-Alder reaction between cyclohexadiene and acrolein using organocatalyst 51 in ionic liquids.

Meracz I, Oh T (2003) Asymmetric Diels-Alder reactions in ionic liquids. Tetrahedron Lett 44 6465-6468... 

The intramolecular Diels-Alder reaction is most frequently used in natural product total synthesis, and numerous examples will be described in the synthetic utility section. As with the intermolecular variant, intramolecular reactions are highly regioselective and stereoselective and participate in hetero, inverse electron demand, and asymmetric Diels-Alder reactions. One report from 2008 describes the investigation of an intramolecular hetero Diels-Alder reaction in ionic liquids. ... 

Herrmann WA, Goossen LJ, Koecher C (1996) Heterocyclic carbenes. 9. Chiral heterocyclic carbenes in asymmetric homogeneous catalysis. Angew Chem Int Ed 35 2805-2807 Earle MJ, McCormac PB, Seddon KR (1999) Diels-Alder reactions in ionic liquids. Green Chem 1 23-25... 

Chiral enamine, dienamine, and trienamine intermediates have been shown to catalyse asymmetric Diels-Alder reactions via HOMO activation. These Diels-Alder reactions generally occur with high chemo-, regio-, and stereo-selectivities. ° The effect of the viscosity of pyridinium-based ionic liquids, with tetrafluoroborate and bis(trifluorosulfonimide) anions, on the kinetics of intra- and inter-molecular Diels-Alder reactions has been investigated. Results show that the intramolecular cycloaddition reaction is less susceptible to viscosity variations than the intermolecular reaction. 

Then the potential for asymmetric induction of some of these chiral ionic liquids was investigated. The aza Diels-Alder cycloaddition between the enantiomericaUy pure (/ )-imine 31 and the Danishefsky s diene 32 was chosen as model asymmetric reaction (Scheme 8). The reaction was performed at room temperature for 5 h using 0.5 equiv. of ionic liquid and 1.5 equiv. of diene. In the absence of chiral ILs, the same coupling required a Lewis acid catalyst (0.1 equiv. of ZnC ) and afforded the main product 33 in 60% yield and low diastereoselectivity (32% de). 

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