Diels-Alder 2-methoxybutadiene

Woodward and Hoffmann pointed out that the Diels-Alder reaction involved bonding overlap of the highest-occupied molecular orbital (HOMO) on the diene and the lowest-unoccupied molecular orbital (LUMO) on the dienophile. Display the HOMO for 2-methoxybutadiene. Where is it localized Display the LUMO for acrylonitrile. Where is it localized Orient the two fragments such that the HOMO and LUMO best overlap (A clearer picture is provided by examining-the HOMO map for 2-methoxybutadiene and the LUMO map for acrylonitrile.) Which product should result ... 

A convenient synthetic route to obtain these compounds is the thermal Diels Alder cycloaddition of 1 -methoxybutadiene (18b) with carbonyl compounds, but this route is limited to aldehydes activated by an electron-withdrawing substituent. Non-activated carbonyl compounds require drastic conditions or fail to react. Application of high pressure overcomes this limitation. 

Scheme 5.22 Al-catalysed Diels-Alder reactions between 2-methoxybutadiene and A -arylmaleimides with bis(sulfonamides) ligands.

Chiral (.S, .S )-diazaaluminolidine catalyst brought about the first highly enantioselective catalytic Diels-Alder reaction of an achiral C2v-symmetric dienophile with an achiral diene. Addition of 2-methoxybutadiene to A-o-tolylmaleimide in the presence of 20 mol % (5,5)-diazaaluminolidine gave rise to the cycloadduct in 98% yield and 93% ee one recrystallization from i-PrOH-hexane furnished the enantiomerically pure compound [57] (Eq. 8A.34). The Diels-Alder reaction of 2-((trimethylsilyl)methyl)butadiene and A-aryimaleimide promoted by this catalyst has been successfully applied to the enantioselective total synthesis of Gracilins B and C [58],... 

The Rates of Diels-Alder Reactions. Most Diels-Alder reactions require that the dienophile carries a Z-substituent before they take place at a reasonable rate. Butadiene 6.144 will react with ethylene, but it needs a temperature of 165 °C and high pressure, whereas the reaction with acrolein is faster, taking less time at a lower temperature. An X-substituent on the diene, on C-l or C-2, increases the rate further, with 1-methoxybutadiene 6.145 and 2-methoxybutadiene 6.146 reacting with acrolein at lower temperatures. Times and temperatures are not a reliable way of measuring relative rates, but these four reactions were taken to the point where the yields of isolated product are close to 80%. 

The first example of an asymmetric Diels-Alder reaction of a maleimide was reported by Corey, Sarshar, and Lee, who used the same catalyst system [59], The catalyst and maleimide were optimized for the cycloaddition with 2-methoxybutadiene as shown in Sch. 34. For high asymmetric induction it was found that that 3,5-dimethyl substituents... 

The first report of a chiral aluminum Lewis acid employed in a heteroatom Diels-Alder reaction utilized Koga s mentholoxy dichloroaluminum catalyst 4 [75]. trans-Piperylene and 1-methoxybutadiene were reacted with n-butyl glyoxalate and diethyl mesoxalate the results are summarized in Sch. 46. The asymmetric induction and chemical yield in these reactions are quite poor but the authors did find that moderate asymmetric induction could be obtained from reactions catalyzed by Eu(hfc)3. 

The 1,3-dithiolane 1,3-dioxide 365 was also investigated in the Diels-Alder reaction with a range of simple dienes (cyclopentadiene, 1-methoxybutadiene, l-methoxy-3-trimethylsilyloxybutadiene, furan) <1995JOC4962, 1998J(P1)2771> and 1,3-dipolar cycloadditions with A - /t-butyl-(7-phenyl nitrone <1998JOC3481> or 3-oxidopyr-idinium betaines <20030BC1884>. 

Roberson, M., Jepsen, A. S., Jorgensen, K. A. On the mechanism of catalytic enantioselective hetero-Diels-Alder reactions of carbonyl compounds catalyzed by chiral aluminum complexes-a concerted, step-wise or Mukaiyama-aldol pathway. Tetrahedron 2001, 57, 907-913. Monnat, F., Vogel, P., Rayon, V. M., Sordo, J. A. Ab Initio and Experimental Studies on the Hetero-Diels-Alder and Cheletropic Additions of Sulfur Dioxide to (E)-I-Methoxybutadiene A Mechanism Involving Three Molecules of S02. J. Org. Chem. 2002, 67, 1882-1889. 

Stereospecificity, the property that the stereochemistry of the starting materials determines the stereochemistry of the product, is one of the hallmarks of pericyclic reactions. It is possible to draw two-step nonconcerted, polar or free-radical mechanisms for many pericyclic reactions, but these two-step mechanisms fail to account for the stereospecificity of the reactions. For example, a two-step polar mechanism can be drawn for the Diels-Alder reaction between 2-methoxybutadiene (a nucleophile) and ethyl cA-crotonatc (an electrophile). This mechanism proceeds through a dipolar intermediate in which one new cr bond has formed. In this intermediate, there is free rotation about the two C atoms of the dienophile, so the cis stereochemical relationship between the Me and CC Et groups is expected to be lost in the product. In fact, though, the product is exclusively cis. This finding does not completely rule out a polar mechanism— it is possible that the intermediate exists but that ring closure occurs more quickly than rotation about the cr bond—but it does limit the lifetime of the dipolar intermediate to such an extent that one can say practically that it does not exist. 

In the Diels-Alder reaction of trans- 1-methoxybutadiene with ethyl acrylate, either the 1,2- or the 1,3-disubstituted product can be obtained in principle. The 1,3-disubstituted product is thermodynamically more stable (less steric hindrance), but the kinetic product is the 1,2-disubstituted compound. The easiest way to explain this phenomenon is to note that C4 of the diene is nucleophilic, and C2 of the dienophile (i.e., the /1-carbon) is electrophilic. Combination of C4diene with C2dienophiie gives the observed product. 

Consider the Diels-Alder reaction between 1-methoxybutadiene and ethyl acrylate. The major product has the MeO and CC Et groups on adjacent C atoms. A reaction that is stereospecific with respect to each component could give either the cis or the trans product. The TS leading to the product in which the substituents are trans is clearly less sterically encumbered than the other TS, and so one would predict that the trans product is predominantly obtained. However, the major product is the one in which the groups are cis. 

Table 5.1 High pressure Diels-Alder reactions of (E)-l-acetoxy- (18a) and (E)-l-methoxybutadiene (18b) with acrylic and crotonic dienophiles...

An important development in the hetero Diels-Alder reaction came when Jurczak used high pressure to help improve the reactivity of dienes with aldehydes. 1-Methoxybutadiene, for example, was shown to react at 15-25 kbar (I bar = l(X) kPa) with a variety of unactivated aldehydes. - These reactions give predominantly endo adducts and allow for the use of simple alkyl and aromatic aldehydes as dienophiles. Jurczak also realized the importance of this reaction in the synthesis of carbohydrates and applied it to the construction of simple monosaccharide derivatives (see Section 2.5.2. ). " ... 

In the Diels-Alder reaction of rrans-l-methoxybutadiene with ethyl acrylate, either the 1,2- or the 1,3-disubstituted product can be obtained in principle. The... 

A less-common activation parameter, the volume of activation (AF ), has been determined for a few Diels-Alder reactions carried out under pressure in liquid phase. The processes are cyclopentadiene dimerisation , isoprene dimerisation , addition of 2,3-dimethylbutadiene to butyl acrylate , addition of cyclopentadiene to dimethyl acetylene dicarboxylate , and addition of maleic anhydride to 1,3-cyclohexadiene, /rans-l-methoxybutadiene and isoprene . Activation volumes are negative, i.e. the reacting systems contract on passing from the initial to the transition state. In some cases the transition state appears to be even smaller than the adduct, independently of the solvent . Some of these experimental results gave rise to controversial interpretations however, the most recent ones favour a concerted four-center mechanism for the reaction. 

The hetero-Diels-Alder (HDA) reaction of 2,3-dimethylbuta-1,3-diene and cyclohexa-1,3-diene with ethyl glyoxylate catalysed by chiral Zn(II) complexes yields both the dihydropyran and the ene product, the former predominating. The enantiomeric excess, which can reach 87%, is dependent on the solvent as well as the catalyst <97JCS(P1)2345>. Use of (Rs,E)-3-[(15)-isoborneol-10-sulfinyl]-l-methoxybutadiene gives the 5,6-dihydropyran with good endo and facial diastereoselectivity <97TA2989>. Scandium(III) perfluoro-octanesulfonate is an efficient catalyst in the HDA reaction of aldehydes with non-activated dienes <97BCJ1421>. 

The hetero-Diels-Alder reaction of 1-methoxybutadiene with aldehydes normally requires high pressures (>15 kbar), and the use of Lewis acid catalysts such as ZnCl2 and BF. Et20 causes polymerization of the diene. However, by using the mild Lewis acids such as... 

The high-pressure Diels-Alder reaction of ketones with 1-methoxybutadiene yields the masked a,/3-unsaturated aldehyde (30). ° Under similar conditions, the highly functionalized cyclohexene (31) may be obtained [equation (6)]."°... 

The difference in reactivity between aldehyde and ketone groups is illustrated by the Diels-Alder adduct between acrolein and 2-methoxybutadiene (5) which on treatment with methanol and ammonium chloride gives the keto-acetal (6) [39], while... 

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