Dienes electron-deficient

D-A rxns with electron deficient dienes and electron rich dienophiles also work well. These are refered to as reverse demand D-A rxns. 

A major difficulty with the Diels-Alder reaction is its sensitivity to sterical hindrance. Tri- and tetrasubstituted olefins or dienes with bulky substituents at the terminal carbons react only very slowly. Therefore bicyclic compounds with polar reactions are more suitable for such target molecules, e.g. steroids. There exist, however, several exceptions, e. g. a reaction of a tetrasubstituted alkene with a 1,1-disubstituted diene to produce a cyclohexene intermediate containing three contiguous quaternary carbon atoms (S. Danishefsky, 1979). This reaction was assisted by large polarity differences between the electron rich diene and the electron deficient ene component. 

In Diels-Alder reactions a nitroolefin may function as an electron-deficient ene com-onent or a 1,2-dihydropyridine derivative may be used as a diene component. Both types of iactants often yield cyclic amine precursors in highly stereoselective manner (R.K. Hill, 1962 i. BOchi, 1965, 1966A). 

In the case of vinylfurans and vinylpyrroles there is the possibility of cycloaddition involving either the cyclic diene system or the diene system including the double bond. 2-Vinylfuran reacts in high yield with maleic anhydride in ether at room temperature to form the adduct involving the exocyclic double bond. Similarly, 2- and 3-vinylpyrroles react with 7T-electron-deficient alkenes and alkynes under relatively mild conditions to give the corresponding tetrahydro- and dihydro-indoles (Scheme 51) (80JOC4515). 

The participation of a single double bond of a heterocycle is found in additions of small and large rings azirines (Section 5.04.3.3) and thietes (Section 5.14.3.11) furnish examples. Azepines and nonaromatic heteronins react in this mode, especially with electron deficient dienes (Scheme 16 Section 5.16.3.8.1). 

A more efficient agent than peroxy compounds for the epoxidation of fluoro-olefins with nonfluonnated double bond is the hypofluorous acid-acetomtrile complex [22] Perfluoroalkylethenes react with this agent at room temperature within 2-3 h with moderate yields (equation 13), whereas olefins with strongly electron-deficient double bond or electron-poor, sterically hindered olefins, for example l,2-bis(perfluorobutyl)ethene and perfluoro-(l-alkylethyl)ethenes, are practically inert [22] Epoxidation of a mixture of 3 perfluoroalkyl-1-propenes at 0 C IS finished after 10 mm in 80% yield [22] The trifluorovinyl group in partially fluorinated dienes is not affected by this agent [22] (equation 13)... 

Halogen-free A/-acyl aldimines and N-acyl ketiimnes tautomenze readily to give enamides [J6] In contrast, perfluonnatedyV-acylimines are stable compounds These electron-deficient itnmes not only exhibit high thermal stability but also show umque properties both as electrophiles and as strongly polanzed hetero-1,3-dienes... 

Cycloaddition reactions where bis(trifluoromethyl)-substituted hetero-1,3-dienes act as dienophiles have been descnbed for open-chain and cyclic dienes [115, 126, 127] The balance of the diene -dienophile activity of bis(tnfluoro-methyl)-substituted hetero-l,3-dienes can be influenced strongly by the substituents bonded to the inuno nitrogen atom For instance, A/-(arylsulfonyl) denvatives of tnfluoroacetaldimine and hexafluoroacetone imine do not act as dienes but exhibit only the dienophile reactivity of electron deficient imines [5 229, 234,235, 236 237] (equation 52)... 

The normal electron-demand reaction is a HOMOdiene-LUMOdienophUeelectron-rich dienes and electron-deficient dienophiles (Scheme 4.2, left dotted line). The inverse electron-demand cycloaddition reaction is primarily controlled by a LUMOdiene HOMOdienophiie inter-... 

The [ 2 + 4]-cycloaddition reaction of aldehydes and ketones with 1,3-dienes is a well-established synthetic procedure for the preparation of dihydropyrans which are attractive substrates for the synthesis of carbohydrates and other natural products [2]. Carbonyl compounds are usually of limited reactivity in cycloaddition reactions with dienes, because only electron-deficient carbonyl groups, as in glyoxy-lates, chloral, ketomalonate, 1,2,3-triketones, and related compounds, react with dienes which have electron-donating groups. The use of Lewis acids as catalysts for cycloaddition reactions of carbonyl compounds has, however, led to a new era for this class of reactions in synthetic organic chemistry. In particular, the application of chiral Lewis acid catalysts has provided new opportunities for enantioselec-tive cycloadditions of carbonyl compounds. 

The coordination of the dienophile to a Lewis acid (in the calculations a proton was used as the Lewis acid) leads also to an increase in regioselectivity. The re-gioselectivity of reactions of electron-rich, or conjugated dienes, with electron-deficient dienophiles is also controlled hy the diene HOMO-dienophile LUMO interaction. From Fig. 8.2 it appears that the difference in magnitudes of the LUMO coefficients at carhon atoms 1 and 2 of acrolein (Ci -C2 = 0.20) is smaller than the same difference for protonated acrolein (Ci -C2 = 0.30-0.43) so that the reaction of the latter should he considerable more regioselective than the former in accordance with the experimental results [3]. 

Nitro compounds have been converted into various cyclic compounds via cycloaddidon reactions. In particular, nitroalkenes have proved to be nsefid in Diels-Alder reactions. Under thermal conditions, they behave as electron-deficient alkenes ind react v/ith dienes to yield 3-nitrocy-clohexenes. Nitroalkenes c in also act as heterodienes ind react v/ith olefins in the presence of Lewis acids to yield cyclic alkyl nkronates, which undergo [3- 2 cycloaddidon. Nitro compounds are precursors for nitnie oxides, alkyl nitronates, and trialkylsilyl nitronates, which undergo [3- 2 cycloaddldon reacdons. Thus, nitro compounds play important roles in the chemistry of cycloaddidon reacdons. In this chapter, recent developments of cycloaddinon chemistry of nitro compotmds and their derivadves are summarized. 

Electron-deficient 1,3-dienes are known to react when heated with metho-xy(aryl)- or methoxy(alkyl)carbene complexes to afford vinylcyclopropane derivatives with high regioselectivity and diastereoselectivity [8a, 24]. Cyclo-propanation of the double bond not bearing the acceptor functional group and... 

Small amounts of cyclopentene derivatives are detected in cyclopropanation reactions of electron-deficient dienes, but they may result from thermal rearrangement of the corresponding vinyl cyclopropanes and not from a direct [4+1] cycloaddition... 

The unique power of Hoveyda s recyclable ruthenium catalyst D in RCM with electron-deficient and sterically demanding substrates is illustrated in Honda s total synthesis of the simple marine lactone (-)-malyngolide (54), which contains a chiral quaternary carbon center (Scheme 10) [35]. Attempted RCM of diene 52 with 5 mol% of NHC catalyst C for 15 h produced the desired... 

The reactivity of neutral dienophiles is greatly increased by converting them to the corresponding cation radicals because these highly electron-deficient species can then react readily with dienes. 

Ethylene disulfonyl-1,3-butadiene (43) is an example of an outer-ring diene with a non-aromatic six-membered heterocyclic ring containing sulfur. It is prepared by thermolysis of sulfolenes in the presence of a basic catalyst. It is very reactive [43] and even though it is electron-deficient, it readily reacted with both electron-rich and electron-poor dienophiles (Equation 2.15). 

Spanish researchers [32] also noted a considerable improvement upon sonica-tion of Diels-Alder reactions of l-dimethylamino-3-methyl-l-azadiene 44 with a variety of electron-deficient dienophiles by using diene as solvent or in acetonitrile (Scheme 4.9). Ultrasound irradiation which allows mild reaction conditions gave good to excellent yields. 

Diels-Alder cycloadditions involving norbomene 57 [34], benzonorbomene (83), 7-isopropylidenenorbomadiene and 7-isopropylidenebenzonorbomadiene (84) as dienophiles are characterized as inverse-electron-demand Diels-Alder reactions [161,162], These compounds react with electron-deficient dienes, such as tropone. In the inverse-electron-demand Diels-Alder reaction, orbital interaction between the HOMO of the dienophile and the LUMO of the diene is important. Thus, orbital unsymmetrization of the olefin it orbital of norbomene (57) is assumed to be involved in these top selectivities in the Diels-Alder cycloaddition. 

Nakayama and coworkers reported that 3,4-di-tert-butylthiophene 1-oxide 114 is thermally stable but still an extremely reactive substrate. They reported that the Diels-Alder reactions of 114 with varieties of electron-deficient and electron-rich dienophiles took place exclusively at the syn-n-face of the diene with respect to the S=0 bond (Scheme 53) [62, 63]. 

Substituted 2-aza-l-(dimethylamino)-3-(inethylthio)-1,3-dienes react readily with a variety of electron-deficient dienophiles to give pyridine derivatives (e.g., 26)... 

This behaviour is similar to that reported for the 2-isomers <94JCS(P1)3129>, but it is now shown that 2-benzothiopyrylium salts can behave as electron deficient dienes affording tricyclic molecules such as (31) and (32) by a [4++2] cycloaddition <96CC2185>. 

Various 1,4-oxathiins have been converted to the sulfoxides in a highly stereoselective reaction. The sulfoxides undergo a thermal retro-Diels-Alder reaction to ot,a -dioxosulrines which can behave both as electron deficient dienes and as dienophiles, affording different oxathiins and dihydrothiopyran 1-oxides, respectively <96T12233>. In like manner, o-thioquinone 5-oxides have been generated and they too exhibit diene and dienophile behaviour <96T12247>. 

The hybrid cyclic pentayne 181 underwent Diels-Alder reaction with the electron-deficient diene tetrachlorothiophene 1,1-dioxide 192, but only at one of the two triple bonds of the 1,3-diyne moiety. This was followed by loss of SO2 to give the tetrachlorobenzannelated cyclotetradecenetetrayne 193 (Scheme 37) [18]. 

Release and Reactivity of tf-o-QMs Although the r 2-o-QM Os complexes 11 are stable when exposed to air or dissolved in water, the quinone methide moiety can be released upon oxidation (Scheme 3.8).16 For example, reaction of the Os-based o-QM 12 with 1.5 equivalents of CAN (ceric ammonium nitrate) in the presence of an excess of 3,4-dihydropyran led to elimination of free o-QM and its immediate trapping as the Diels-Alder product tetrahydropyranochromene, 14. Notably, in the absence of the oxidizing agent, complex 12 is completely unreactive with both electron-rich (dihydropyran) and electron-deficient (A-methylmaleimide) dienes. 

Notably, not only electron-rich dienes, but also electron-deficient dienes nicely participate in the reaction and react benzaldehyde with similar ease and in a similar sense of stereoselectivity. For example, methyl sorbate provides the 1,2-anti isomer exclusively in good yield with excellent regio- and stereoselectivity (run 7). The regioselectivity reacting at Cl of the diene skeleton might stem from electronic factors rather than from other factors such as coordination the coordination of the ester oxygen to nickel metal center, since ( , )-l-(methoxymethyl)-4-methyl-l,3-butadiene and (E,E)-1-(hydroxymethyl)-4-methyl-l,3-butadiene furnish the C4 adducts selectively together with the Cl adducts as minor products (not shown). Notably,... 

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