Diels-Alder reactions titanium

Yamamoto et al. have reported a chiral helical titanium catalyst, 10, prepared from a binaphthol-derived chiral tetraol and titanium tetraisopropoxide with azeotropic removal of 2-propanol [16] (Scheme 1.22, 1.23, Table 1.9). This is one of the few catalysts which promote the Diels-Alder reaction of a-unsubstituted aldehydes such as acrolein with high enantioselectivity. Acrolein reacts not only with cyclo-pentadiene but also 1,3-cyclohexadiene and l-methoxy-l,3-cyclohexadiene to afford cycloadducts in 96, 81, and 98% ee, respectively. Another noteworthy feature of the titanium catalyst 10 is that the enantioselectivity is not greatly influenced by reaction temperature (96% ee at... 

Another chiral titanium reagent, 11, was developed by Corey et al. [17] (Scheme 1.24). The catalyst was prepared from chiral ris-N-sulfonyl-2-amino-l-indanol and titanium tetraisopropoxide with removal of 2-propanol, followed by treatment with one equivalent of SiCl4, to give the catalytically-active yellow solid. This catalyst is thought not to be a simple monomer, but rather an aggregated species, as suggested by NMR study. Catalyst 11 promotes the Diels-Alder reaction of a-bro-moacrolein with cyclopentadiene or isoprene. 

I 1 Catalytic Asymmetric Diels-Alder Reactions 1.2.3.6 Titanium... 

The Diels-Alder reaction catalyzed by this chiral titanium catalyst 31 has wide generality (Scheme 1.53, 1.54, Table 1.22, 1.23). Acryloyl- and fumaroyl-oxazolidinones react with isoprene giving cycloadducts in high optical purity. 2-Ethylthio-l,3-buta-diene can also be successfully employed as the diene [42]. 

Application of this catalytic process was extended to asymmetric intramolecular Diels-Alder reactions. Synthetically useful intermediates with octalin and decalin skeletons were obtained in high optical purity by use of a catalytic amount of the chiral titanium reagent [45] (Scheme 1.57, Table 1.25). The core part of the mevi-nic acids was enantioselectively synthesized by use of this asymmetric intramolecular reaction [46] (Scheme 1.58). 

Several aluminum- and titanium-based compounds have been supported on silica and alumina [53]. Although silica and alumina themselves catalyze cycloaddition reactions, their catalytic activity is greatly increased when they complex a Lewis acid. Some of these catalysts are among the most active described to date for heterogeneous catalysis of the Diels-Alder reactions of carbonyl-containing dienophiles. The Si02-Et2AlCl catalyst is the most efficient and can be... 

Inverse electron-demand Diels-Alder reaction of (E)-2-oxo-l-phenylsulfo-nyl-3-alkenes 81 with enolethers, catalyzed by a chiral titanium-based catalyst, afforded substituted dihydro pyranes (Equation 3.27) in excellent yields and with moderate to high levels of enantioselection [81]. The enantioselectivity is dependent on the bulkiness of the Ri group of the dienophile, and the best result was obtained when Ri was an isopropyl group. Better reaction yields and enantioselectivity [82, 83] were attained in the synthesis of substituted chiral pyranes by cycloaddition of heterodienes 82 with cyclic and acyclic enolethers, catalyzed by C2-symmetric chiral Cu(II) complexes 83 (Scheme 3.16). 

Keywords asymmetric Diels-Alder reactions, chiral titanium reagent... 

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)). 

Annual Volume 71 contains 30 checked and edited experimental procedures that illustrate important new synthetic methods or describe the preparation of particularly useful chemicals. This compilation begins with procedures exemplifying three important methods for preparing enantiomerically pure substances by asymmetric catalysis. The preparation of (R)-(-)-METHYL 3-HYDROXYBUTANOATE details the convenient preparation of a BINAP-ruthenium catalyst that is broadly useful for the asymmetric reduction of p-ketoesters. Catalysis of the carbonyl ene reaction by a chiral Lewis acid, in this case a binapthol-derived titanium catalyst, is illustrated in the preparation of METHYL (2R)-2-HYDROXY-4-PHENYL-4-PENTENOATE. The enantiomerically pure diamines, (1 R,2R)-(+)- AND (1S,2S)-(-)-1,2-DIPHENYL-1,2-ETHYLENEDIAMINE, are useful for a variety of asymmetric transformations hydrogenations, Michael additions, osmylations, epoxidations, allylations, aldol condensations and Diels-Alder reactions. Promotion of the Diels-Alder reaction with a diaminoalane derived from the (S,S)-diamine is demonstrated in the synthesis of (1S,endo)-3-(BICYCLO[2.2.1]HEPT-5-EN-2-YLCARBONYL)-2-OXAZOLIDINONE. 

Perhaps the most attractive method of introducing enantioselectivity into the Diels-Alder reaction is to use a chiral catalyst in the form of a Lewis acidic metal complex. In recent years, this area has shown the greatest progress, with the introduction of many excellent catalytic processes. Quite a number of ligand-metal combinations have been evaluated for their potential as chiral catalysts in Diels-Alder reactions. The most commonly used metals are boron, titanium, and aluminum. Copper, magnesium, and lanthanides have also been used in asymmetric catalytic Diels-Alder reactions. 

Chiral titanium catalyst for asymmetric Diels-Alder reactions. A Japanese group2 recently reported that a chiral titanium reagent (1), prepared in situ from TiCl2(0-f-Pr)2 and the chiral diol 2, derived from L-tartaric acid, in combination... 

In 1990, Choudary [139] reported that titanium-pillared montmorillonites modified with tartrates are very selective solid catalysts for the Sharpless epoxidation, as well as for the oxidation of aromatic sulfides [140], Unfortunately, this research has not been reproduced by other authors. Therefore, a more classical strategy to modify different metal oxides with histidine was used by Moriguchi et al. [141], The catalyst showed a modest e.s. for the solvolysis of activated amino acid esters. Starting from these discoveries, Morihara et al. [142] created in 1993 the so-called molecular footprints on the surface of an Al-doped silica gel using an amino acid derivative as chiral template molecule. After removal of the template, the catalyst showed low but significant e.s. for the hydrolysis of a structurally related anhydride. On the same fines, Cativiela and coworkers [143] treated silica or alumina with diethylaluminum chloride and menthol. The resulting modified material catalyzed Diels-Alder reaction between cyclopentadiene and methacrolein with modest e.s. (30% e.e.). As mentioned in the Introduction, all these catalysts are not yet practically important but rather they demonstrate that amorphous metal oxides can be modified successfully. 

The Diels-Alder reaction outlined above is a typical example of the utilization of axially chiral allenes, accessible through 1,6-addition or other methods, to generate selectively new stereogenic centers. This transfer of chirality is also possible via in-termolecular Diels-Alder reactions of vinylallenes [57], aldol reactions of allenyl eno-lates [19f] and Ireland-Claisen rearrangements of silyl allenylketene acetals [58]. Furthermore, it has been utilized recently in the diastereoselective oxidation of titanium allenyl enolates (formed by deprotonation of /3-allenecarboxylates of type 65 and transmetalation with titanocene dichloride) with dimethyl dioxirane (DMDO) [25, 59] and in subsequent acid- or gold-catalyzed cycloisomerization reactions of a-hydroxyallenes into 2,5-dihydrofurans (cf. Chapter 15) [25, 59, 60],... 

Brimble and coworkers172 reported the asymmetric Diels-Alder reactions between quinones 265 bearing a menthol chiral auxiliary and cyclopentadiene (equation 73). When zinc dichloride or zinc dibromide was employed as the Lewis acid catalyst, the reaction proceeded with complete endo selectivity, but with only moderate diastereofacial selectivity affording 3 1 and 2 1 mixtures of 266 and 267 (dominant diastereomer unknown), respectively. The use of stronger Lewis acids, such as titanium tetrachloride, led to the formation of fragmentation products. Due to the inseparability of the two diastereomeric adducts, it proved impossible to determine which one had been formed in excess. 

Engler and colleagues256 demonstrated that the way in which catalyst 406 is prepared has a strong effect on the regioselectivity and enantioselectivity of quinone Diels-Alder reactions. The most effective catalyst was prepared from a 1 1 1 mixture of titanium tetrachloride, titanium tetraisopropoxide and chiral diol 416. The cycloadditions of 2-methoxy-l,4-benzoquinones such as 414 with simple dienes to give adducts like 415 proceeded with high yields and enantioselectivities of up to 80% ee using this catalytic system (equation 123). 

Yamamoto and colleagues prepared chiral titanium catalyst 420 from titanium tetraisopropoxide and chiral binaphthol 419 (equation 126). This catalyst gave high asymmetric inductions in various Diels-Alder reactions of a,/J-unsaturated aldehydes with cyclopen-tadiene and 1,3-cyclohexadiene260. 

The Diels-Alder reaction of enantiomerically pure chiral aery he esters with cyclopen-tadiene leads to a pair of diastereomers. Their ratio depends strongly on the choice and amount of Lewis acid catalyst (Scheme 8)117. While titanium tetrachloride leads preferentially to the (2A )-diastercorner with high selectivity, ethyl aluminium dichloride gives the (2S )-diastereomer in only 56% de. 

A catalytic asymmetric Diels-Alder reaction was developed by using 3-(3-borylpropenoyl)oxazolidin-2-ones 146. In the reactions of butadiene, isoprene, or 2-methyl-l,3-pentadiene and 146, in the presence of a chiral titanium catalyst 147, the cyclohexene derivatives 148 were formed. 

One of the efficient method for constructing carbohydrates is the Diels-Alder reaction, which gives a variety of important synthetic intermediates for the synthesis of cyclitol derivatives. We therefore were interested in the development of asymmetric Diels-Alder reaction by the use of chiral titanium reagents. 

Since high enantioselectivity was achieved by employing two molar equivalents of the chiral titanium reagent generated from 17b, the asymmetric Diels-Alder reaction of various oxazolidone derivatives of a,8-unsaturated acids and cyclopentadiene was studied. The results are listed in Table 4. With the exception of the acryloyl derivative 15b, various dienophiles reacted with cyclopentadiene to give the endo-adducts 1 in high optical purity. 

The present titanium reagent was noted to exhibit a wide applicability to the asymmetric Diels-Alder reaction of various prochiral dienes and dienophiles. 

Compared to the previous procedure in which 2 molar equivalents of the chiral titanium was employed, almost the same level of enantioselectivity was attained in the Diels-Alder reaction of 15a, and the optical purity of the cycloadduct 18b was improved significantly. 

Table 5, Asymmetric Diels-Alder Reaction Using Catalytic Amount of Titanium Reagent...

The task of assaulting 72 was bestowed upon Chin Wing Chan whose undergraduate research work was under my direction. The key feature of our route to 72 doubtlessly revolved around the combined use of the Diels-Alder reaction in conjunction with low-valent-titanium deoxygenation. Thus, the known 75 was brominated with NBS to afford the dibromide 76, which was then dehydrobromi-nated in the usual way to give presumably the strained alkyne 77. As expected, all efforts to isolate 77 as a stable molecule were fruitless. However, 77 could be tr ped by furan to form the endoxide 78. Low-valent-titanium deoxygenation converted 78 to the desired molecule 72 (Scheme 16). ... 

Another method of functionalizing 72 was initiated by catalytically hydrogenating 78 to 79. Thermolysis of 79 at 220 °C under vacuum resulted in an ethylene extrusion to generate furan 80. Diels-Alder reaction of 80 with dimethyl acetyle-nedicarboxylate (DMAD) provided endoxide 81, which on subsequent deoxygenation with low-valent titanium gave ester 82 (Scheme 17). ... 

An important catalyst-substrate intermediate that applies to both the TiCl2-TADDOLate catalyzed 1,3-dipolar cycloadditions and Diels-Alder reactions has been isolated and characterized (353). The crystalline compound 248 has been characterized by X-ray analysis, showing that the oxazolidinone is coordinated to the titanium center in a bidentate fashion (Scheme 12.75). The four oxygen atoms. 

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