Hetero Danishefsky diene

A difluorinated analogue of the Danishefsky diene has been prepared by reductive defluorination with Mg(0) of an a,/i-unsaturated trifluoromethylketone. Its use in a hetero-Diels-Alder reaction (including asymmetric version) can lead to oxygen- and nitrogen-containing heterocycles (Figure 2.25)." ... 

ZnCl2 was also used for a hetero-Diels-Alder reaction of 192 with Danishefsky diene. The dihydropyranone was obtained in 61% yield and good diastereoselectivity (Equation 59) <1998T14573>. 

New possibilities in hetero-Diels-Alder condensation have been opened by the introduction of highly active l-methoxy-3-trimethylsilyloxy-, 4-benzoyIoxy-l-methoxy-3-trimethylsilyloxy-, and 2-acetoxy-l-alkoxy-3-trimethylsilyloxy-l,3-butadienes ( Danishefsky dienes, 5). These compounds readily react under atmospheric pressure, in the presence of Lewis acids, with normal aldehydes (e.g., acetaldehyde, benzaldehyde, furfural) to furnish 2,3-disubstituted or 2,3,5-trisubstituted derivatives of 2,3-dihydro-4H-pyran-4-one 7 capable of readily functionalizing to sugars (Scheme 5) [26]. This approach... 

The hetero-DielsAlder reaction (hDA) using iminium species has been commonly used for the synthesis of reduced pyridines and pyridones . The aza-1,3-butadiene 107 was employed in hDA reaction to synthesize the key intermediate 108 in the total synthesis of the pyridine-based natural product piericidin (Scheme 60) <2005JA15704>. The reaction of Danishefskys diene with N-functionalized imine 109 in the presence of (A)-BINOL zinc complex has been utilized to produce 4-piperidones 110 in moderate to high enantioselectivity (Scheme 61) <2004SL711>. 

The B-alkylated CAB catalyst (3) is easily prepared in situ by mixing a 1 1 molar ratio of tartaric acid derivative and phenyl-boronic acid in dry propionitrile at room temperature for 0.5 h. The hetero Diels-Alder reaction of aldehydes with Danishefsky dienes is promoted by 20 mol % of this catalyst solution at —78 °C for several hours to produce dihydropyranone derivatives of high optical purity (eq 9). 

We have developed a stable CAB 2 (R = aryl) complex that can be prepared in situ by mixing tartaric acid derivative and arylboronic acid at room temperature. In contrast with 2, R = H, which is both air- and moisture-sensitive, the B-alkylated catalyst 2, R = aryl or alkyl, is stable and can be stored in closed containers at room temperature (Eq. 39). A solution of the catalyst (20 mol %) is effective in catalyzing the hetero Diels-Alder reaction of aldehydes with a Danishefsky diene to produce dihydro-pyrone derivatives of high optical purity (up to 98 % ee) (Eq. 40) [39]. The extent of asymmetric induction is largely dependent on the structure of the boronic acid. In general, bulky phenylboronic acid (R = 2,4,6-Me3CeH2, o-MeOC6H4) results in excellent asymmetric induction. 

Inanaga and coworkers prepared a series of tris[(l )-(-)-l,l -binaphthyl-2,2 -diylphosphato]lanthanides(III) Lnff-lBNPjj as new chiral and stable Lewis acids by the simple treatment of lanthanide(III) chlorides with three equivalent of the optically active sodiirm phosphate at room temperature, and reported the observed catalytic activity [31,32].The asymmetric hetero-Diels-Alder reactions of the Danishefsky diene 5 with benzaldehyde or with 2-naphthaldehyde were successfully performed at 0 °C in the presence of 10 mol % of Sc[(-)BNP]3 to give the corresponding adducts in 77 and 69% chemical yields with 68 and 74% enantiomeric excesses of (l )-(-)-isomers, respectively (Scheme 14). 

By ensconcing an In(III) ion in the A-oxide 55B originated from two homochiral pipe-colinic amides a catalyst for hetero-Diels-Alder reaction involving the Danishefsky diene and aldehydes is obtained. Cr(salen) 149 appears to have similar capability. ... 

Hetero-Diels-Alder reaction. The zirconium complexes of 3,3 -diaryl-BINOL are effective chiral catalysts for the smooth condensation of aldimines with a Danishefsky diene. Linkage of the BINOL moiety to polymer support also provides viable catalysts. 

Hetero-Diels-Alder reaction. In the cyclocondensation of the Danishefsky diene and aldehydes in the presence of 2, a remarkably high asymmetric amplification is realized. 

The Zr-BINOL complexes were effectively utilized for asymmetric aza- and hetero Diels-Alder reactions [lb]. The reaction of imine (27) with Danishefsky diene (113) afforded optically active dihydropyridone (114) in high yield (Equation 52) [7, 57]. A similar reaction was also possible for benzaldehyde and diene (115) (Equation 53), [7, 58] and the corresponding dihydropyranone was obtained in excellent yield with excellent enantioselectivity. In addition, the reaction was applied for total synthesis of natural products [58b]. 

The Diels-Alder reaction has not escaped the attention of chemists interested in asymmetric synthesis. A binaphthyl-based chiral aluminium complex (30) catalyses the hetero Diels-Alder cycloaddition between benzaldehyde and the Danishefsky diene (29), providing the dihydropyrone (32) with excellent selectivity after acid hydrolysis of the initial adduct (31). 0 2] (We will see further applications of chiral binaphthyl ligands in section 6.4.)... 

For these, several chiral Lewis acid catalysts, which have the C-2 symmetry element, were designed and tested for various asymmetric syntheses, and in 1985 we reported a zinc reagent and in 1988 a bulky aluminum reagent (Scheme 8) [15, 16]. The zinc reagent was used for asymmetric cyclization of unsaturated aldehyde and the aluminum catalyst for asymmetric hetero-Diels-Alder reaction with Danishefsky diene. Both catalysts effectively discriminate the enantioface of aldehydes for reactions. 

In(III) salts were used in many studies in the area of hetero Diels-Alder reactions. Frost et al. worked on using In(OTf)3 to catalyze the reactions of aromatic aldehydes and imines with Danishefsky diene [177]. The group found that the use of In(OTf)3 not only gave good yields of the Diels-Alder products in a short time, but also required the least catalyst load. Further competitive studies revealed that the imine is much more reactive than the aldehyde and the group proceeded to... 

The mechanism for the hetero-Diels-Alder reaction of benzaldehyde 9 with the very reactive diene, Danishefsky s diene 10, catalyzed by aluminum complexes has been investigated from a theoretical point of view using semi-empirical calculations [27]. The focus in this investigation was to address the question if the reaction proceeds directly to the hetero-Diels-Alder adduct 11, or if 11 is formed via a Mukaiyama aldol intermediate (Scheme 8.4) (see the chapter dealing with hetero-Diels-Alder reactions of carbonyl compounds). 

Fig. 8.13 Schematic representation of the change in energies for the concerted hetero-Diels-Alder reaction of benzaldehyde with Danishefsky s diene and the step-wise reaction...

The structures along the reaction path in Fig. 8.13 are outlined in Fig. 8.14 starting with benzaldehyde activated by (MeO)2AlMe in the reaction with Danishefsky s diene 10 leading to the transition-state structure for the formation of the al-dol-like intermediate, and finally the formation of the hetero-Diels-Alder adduct. 

Similar transformations have been performed with Danishefsky s diene and glyoxylate esters [85] catalyzed by bis (oxazoHne)-metal complexes to afford the hetero Diels-Alder product in 70% isolated yield and up to 72% ee. Jorgensen [86,87] reported a highly enantioselective, catalytic hetero Diels-Alder reaction of ketones and similar chiral copper(II) complexes leading to enantiomeric excesses up to 99% (Scheme 31, reaction 2). They also described [88] a highly diastereo- and enantioselective catalytic hetero Diels-Alder reaction of /I, y-imsaturated a-ketoesters with electron-rich alkenes... 

Several groups have reported the use of rare earth complexes as catalysts for asymmetric Diels-Alder reaction. Qian and Wang described thus the preparation and use of Yb complexes chelated by Pr-PyBOx to successfully achieve the hetero-Diels-Alder reaction of methyl glyoxylate with Danishefsky s diene in 77% ee and 73% yield (Scheme 37) [98]. 

Bis(trifluoromethanesulfonylamides) ligand was also used by Mikami et al., in 1995, for the lanthanide-catalysed hetero-Diels-Alder reaction of Danishefsky s diene with butyl glyoxylate. This reaction produced the corresponding... 

The montmorillonite KlO-catalyzed aza-Diels-Alder reaction of Danishefsky s diene with aldimines, generated in situ from aliphatic aldehydes and p-anisidine, proceeded smoothly in H20 or in aqueous CH3CN to afford 2-substituted 2,3-dihydro-4-pyridones in excellent yields (Eq. 12.47).115 Also, complex [(PPh3)Ag(CBiiH6Br6)] was shown to be an effective and selective catalyst (0.1 mol% loading) for a hetero-Diels-Alder reaction with Danishefsky s diene and the reaction showed a striking dependence on the presence of trace amounts of... 

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... 

Hetero-Diels-Alder reactions have been succesfully employed for the synthesis of arenoquinolizine systems. For example, as shown in Equation 10, treatment of tetrahydroquinoline 319 with Danishefsky s diene 320 in the presence of a Lewis acid gave the benzo[c]quinolizidine derivative 321 <2000JME3718>. 

Mg11 is often employed in stereoselective reactions. In hetero Diels-Alder reactions of aldehydes with Danishefsky s diene, Mg11 results in good acceleration and stereoselection, and 2,3-coproducts are obtained exclusively (Scheme 6).26 Milder Lewis acidity is necessary for obtaining higher yield and higher stereoselectivity in this reaction, which occurs through a cyclic transition state. 

Finally, the discovery of exceptionally efficient catalysts for solvent-free enantioselective hetero-Diels-Alder reactions was made possible by a combinatorial approach.121 The object was to find a chiral titanium catalyst for the reaction of aldehydes (51) with Danishefsky s diene (91), with formation of cycloadduct (92) in >99% enantipurity (Equation (11)). 

Schaus et al.41 have also reported an asymmetric hetero Diels-Alder reaction of Danishefsky s diene 10042 with aldehyde 101 catalyzed by chromium(III) complex 99 bearing a similar chiral salen ligand. Product 102 is obtained in moderate to good yield and stereoselectivity (Scheme 5-31 and Table 5-5). 

Jorgensen s group reported the aza Diels-Alder reactions in the presence of several chiral catalysts.52 They found that chiral bis(oxazoline) ligands 81, 83, 103, 104, and 105, which were effective in asymmetric oxo hetero Diels-Alder reactions, induced the aza Diels-Alder reaction of a-imino ester with Danishefsky s diene with only poor to moderate enantioselectivity. Selected results are listed in Scheme 5-40. 

Whiting and co-workers (231) reported that the chiral diamine 341Cu(OTf)2 complex is moderately effective in inducing the hetero-Diels-Alder reaction between glyoxylate imine (339) and Danishefsky s diene (334). In acetonitrile as solvent, this reaction provides cycloadduct 340 in 58% yield and 86% ee, Eq. 190. 

Jprgensen and co-workers (253) adapted this catalyst system to the hetero-Diels-Alder reaction between Danishefsky s diene and glyoxylate imine. The Tol-BINAP CuC104 proved to be the optimal catalyst for this reaction, affording the... 

Asymmetric Diels-Alder reactions have also been achieved in the presence of poly(ethylene glycol)-supported chiral imidazohdin-4-one [113] and copper-loaded silica-grafted bis(oxazolines) [114]. Polymer-bound, camphor-based polysiloxane-fixed metal 1,3-diketonates (chirasil-metals) (37) have proven to catalyze the hetero Diels-Alder reaction of benzaldehyde and Danishefsky s diene. Best catalysts were obtained when oxovanadium(lV) and europium(III) where employed as coordinating metals. Despite excellent chemical yields the resulting pyran-4-ones were reported to be formed with only moderate stereoselectivity (Scheme 4.22). The polymeric catalysts are soluble in hexane and could be precipitated by addition of methanol. Interestingly, the polymeric oxovanadium(III)-catalysts invoke opposite enantioselectivities compared with their monomeric counterparts [115]. 

---