Dioxolanes Diels-Alder reactions

At the other extreme of diene reactivity, some dienes are so unreactive that only powerful dienophiles such as PTAD will undergo Diels-Alder reactions with them. Thus, 4,5-dimethylene-l,3-dioxolan-2-one fails to react with TCNE or maleic anhydride, but gives the required Diels-Alder adduct (63%) with PTAD.232 The powerful dienophilic properties of PTAD have... 

Similarly, the diethyl acetal of acrolein undergoes facile Diels-Alder reactions in the presence of triflic acid, although yields are only moderate. 2-Vinyl-l,3-dioxolane is recommended as the reagent of choice because of higher yields.2... 

Z)-4-[(5)-2,2-Dimethyl-l,3-dioxolan -ylmethylene]-2-phenyl-5(47/)-oxazolone 632 can react as a dienophile in diastereoselective Diels-Alder reactions. Thus, 632 undergoes a thermally induced Diels-Alder reaction with cyclic dienes, for example, cyclopentadiene and cyclohexadiene, to afford a mixture of the four... 

The X-ray crystal structure of fZ)-4-[(5)-2,2-dimethyl-l,3-dioxolan -ylmethyl-ene]-2-phenyl-5(4//)-oxazolone has been determined. " The analysis shows an almost planar disposition for the entire molecule with the exception of the dioxolane ring that adopts an envelope conformation. As such, the dioxolane ring is mainly situated on the si,si diastereotopic face of the olefinic bond, a situation that accounts for the observed diastereoselectivity in Diels-Alder reactions. 

Various a,a,a, a -tetraaryl-l,3-dioxolane-4,5-dimethanols have been prepared from (R,R)-tartrate, which are called TADDOLs by Seebach et al. They studied the influence of the Ti catalyst preparation methods, the presence of molecular sieves, and the TADDOL structure in the enantioselective Diels-Alder reaction of acryloyl oxazolidinones [41] (Eq. 8A.22). Seebach also prepared polymer- and dendrimer-bound Ti-TADDOLates and used in catalytic asymmetric cycloadditions [42],... 

The asymmetric Diels-Alder reaction of diene and cyclopentenone derivatives can be promoted by a chiral titanium catalyst prepared in situ from (Pr 0)2TiCl2 and a tartrate-derived o.,a,a, a -tetraalkyl-l,3-dioxolane-4,5-dimethanol [54] (Eq. 8A.31). The resulting adducts can easily be tranformed to estrogens and progestogens. 

The presence or absence of the dioxolane protecting group in dienes dictates whether they participate in normal or inverse-electron-demand Diels-Alder reactions.257 The intramolecular inverse-electron-demand Diels-Alder cycloaddition of 1,2,4-triazines tethered with imidazoles produce tetrahydro-l,5-naphthyridines following the loss of N2 and CH3CN.258 The inverse-electron-demand Diels-Alder reaction of 4,6-dinitrobenzofuroxan (137) with ethyl vinyl ether yields two diastereoisomeric dihydrooxazine /V-oxide adducts (138) and (139) together with a bis(dihydrooxazine A -oxide) product (140) in die presence of excess ethyl vinyl ether (Scheme 52).259 The inverse-electron-demand Diels-Alder reaction of 2,4,6-tris(ethoxycarbonyl)-l,3,5-triazine with 5-aminopyrazoles provides a one-step synthesis of pyrazolo[3,4-djpyrimidines.260 The intermolecular inverse-electron-demand Diels-Alder reactions of trialkyl l,2,4-triazine-4,5,6-tricarboxylates with protected 2-aminoimidazole produced li/-imidazo[4,5-c]pyridines and die rearranged 3//-pyrido[3,2-[Pg.460]

A further example of the use of 2//-thiopyrans as surrogates for m-substituted dienes involves the use of the protected 3,4-dihydio-3-(3-oxobutyl)A//-thiopyranA-onc, 3-[2-(2-methyl-l,3-dioxolan-2-yl)ethyl]-4-[tris(l-methy-lethyl)silyl)oxy-2//-thiopyran 328 as an equivalent of l-ethenyl-2-methylcyclohexene in Diels-Alder reactions. The thiopyran reacted with various maleimides to yield the endo cycloadducts and with methyl propenoate to give the exo adduct under either thermal or Lewis-acid-catalyzed conditions. In the latter case concomitant release of the protected ketone functions occurs, acid-catalyzed cyclization of which generates a fused cyclohexenone ring (Scheme 67). Desulfurization, preferably before the aldol cyclization, leads to derivatives of 2,3,4,4a,5,6,7,8-octahy-dro-4a-methylnaphthalenes < 1997CJC681 >. 

The ability of furan to undergo both the forward and reverse Diels-Alder reaction has been used to synthesize 1,3-dioxoles, and the reaction appears to have wide applicability. In Scheme 42 the synthesis of 2-phenyl-l,3-dioxole is shown. The key to the process is the dialcohol (119), which is obtained from vinylene carbonate as shown. The dialcohol (119) has the potential of serving as an intermediate for a variety of 2-substituted 1,3-dioxolanes (73JA7161). 

Chiral Lewis Acid. These chiral titanium reagents are widely used as chiral Lewis acid catalysts. The Diels-Alder reaction of methyl acrylate and cyclopentadiene affords the endo adduct in moderate enantioselectivity when a stoichiometric amount of the chiral titanium reagent (5) is employed (eq 6). Use of 3-(2-alkenoyl)-l,3-oxazolidin-2-ones as dienophiles greatly improves the optical purity of the cycloadduct when the 2-phenyl-2-methyl-1,3-dioxolane derivative (6) is used as a chiral ligand. Most importantly, the reaction proceeds with the same high enantioselectivity for the combination of various dienophiles and dienes even when 5-10 mol % of the chiral titanium reagent is employed in the presence of molecular sieves 4A (eqs 7 and 8). ... 

Other important titanium alkoxide-based Lewis acids are Ti-TADDOLate (a,a,a, a -tetraaryl-l,3-dioxolane-4,5-dimethanol)ates, among the most effective chiral catalysts for several important asymmetric reactions. These will be discussed in the sections on polymer-supported Diels-Alder reactions (Section 21.10) and alkylations (Section 21.9). 

Tetraaryl-l,3-dioxolane-4,5-dimethanol (TADDOL) ligands synthesized from tartaric acid have been extensively employed by Narasaka as the chiral control element in selective Diels-Alder reactions. Initial experiments were conducted with simple dienes and a,P-unsaturated imides using complex 44 (Scheme 36) [104,105]. Several rather subtle features have contributed to the success of these endeavors 1) the use of the acetophenone-derived dioxolane rather than the ac-etonide resulted in an increase of 20% ee 2) the use of alkyl-substituted benzenes as solvent augmented enantioselectivities relative to more common organic solvents e.g., CH2CI2, THF) [106] 3) use of 4 A molecular sieves was typically required to achieve maximum enantioselectivity. 

Ligands having C2-symnietry have also been used with metals that are undoubtedly octahedral, however the analysis of facial selectivity in octahedral complexes is complicated by several possible competing coordination modes of the dienophile. One class of ligand that has been well studied are the TADDOLs (TADDOL is an acronym for a,a,a, a -tetraaryl-l,3-dioxolane-4,5-dimethanol). Both the Narasaka [236] and the Seebach [228] groups have evaluated a number of TADDOLs as ligands for titanium in the asymmetric Diels-Alder reaction. Table... 

This explanation is described as a mnemonic rule [228], which can only be taken as a first approximation of reality. The same rule can be used to rationalize the topicity of other asymmetric Diels-Alder reactions, such as those employing titanium BINOLate catalysts (Figure 6.18i, [230]), or iron bisoxazoline catalysts (Figure 6.18j,k [206,215]). Although the explanation seems reasonable, the picture is not complete, since it does not account for a number of observations, including the fact that the dioxolane substituents exert an extraordinary effect on catalyst efficiency (c/ Table 6.6, entries 2 and 5). Additionally, both titanium TADDOLate [228] and BINOLate [230] complexes show a nonlinear relationship between enantiomeric purity of the catalyst and that of the product, which suggests that some sort of dimerization phenomenon is involved. 

Many dioxolanes. particularly those where the diisopropylidene unit is used as a protecting group for diols, have already been discussed in Sections 4.2. and 4.3. (derivatives of tartaric acid and carbohydrates). In addition, vinylketene acetals containing the 1,2-dioxolane moiety, e.g., 1, have been prepared from chiral diols, such as l,2-diphenyl-l,2-ethanediol (see Section 4.1. for access to the starting material) by the pathway outlined. This involves selective conversion of the (/ ,/ )-diol to (1 / ,2S )-2-chloro-l, 2-diphenylethanol (with inversion of the configuration)1, followed by esterification with 3-meihyl-2-propenoic acid and base-induced rearrangement2. Such dioxolanes have been used for diastereoselective Diels-Alder reactions (Section D. 1.6.1.1.1.1.4.4.). 

Based on Frechefs work [20], Luis and coworkers [21] studied the influence of the mode of preparation of the polystyrene backbone functionalized with TADDOL (a,a,a, a -tetraaryl-l,3-dioxolane-4,5-dimethanol) 2. This immobilized ligand was loaded with titanium on the topicity of an asymmetric transformation. Here, the Diels-Alder reaction of cyclopentadiene with 3-crotonyl-l,3-oxazolidin-2-one was chosen as a model reaction. The TADDOL ligands were incorporated into the polymeric backbone either by polymerization using functionalized styrene derivative 1 or by grafting and coupling of phenol 2 to Merrifield-type resins (Scheme 7). 

Catioiuc dienophiles, in which the alkene is rendered electron deficient, are good substrates for the Diels-Alder reaction. 2-Vinyl-l,3-dioxolane 13 is very unreactive towards dienes, however, on protonation, the acetal is in equilibrium... 

Narasaka and coworkers used the titanium complex of the TADDOL (a,a,a, a tetraaryl-l,3-dioxolane-4,5-dimethanol) ligand (8.50) to catalyse Diels-Alder reactions of acyloxazolidinones. Thus, the crotonyl derivative (8.51) was... 

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