Dienes with acrolein

Dienol esters of chiral acids have been proposed as chiral dienes. Trost and coworkers [73, 170] have shown that cycloaddition of quinone 9.41 (X - OH) with l-(0-methyImandeloxy)butadiene 1.113 (R = H) is highly stereoselective when catalyzed by B(OAc)3 (Figure 9.47). The cycloaddition of the same diene with acrolein is also selective [387] (Figure 9.47). The replacement of the phenyl substituent of 1.113 by a cyclohexyl group does not affect the selectivity, so x-stacldng does not intervene in transition state [387]. Instead, the diene is probably in a nonfolded conformation (Figure 9.47). 

The moderate Lewis acidity of ruthenium complexes was used to promote catalytic Diels Alder reactions, and notably, enantioselective Diels Alder reactions were performed with ruthenium containing a cyclopentadienyl or indenyl ligand and a chiral P,P-ligand such as (/ )-BINOP-F or 1,2-bis(diphenylphosphinamino) cyclohexane [128-132]. These mild chiral Lewis acids proved to be excellent catalysts for the intermolecular Diels Alder reactions of dienes with acrolein derivatives [128-130] [Eq. (61)] and enones [131] as well as for the intramolecular Diels Alder reaction of suitable trienes [132] [Eq. (62)]. 

Acrolein a.s Dienophile. The participation of acrolein as the dienophile in Diels-Alder reactions is, in general, an exothermic process. Dienes such as cyclopentadiene and l-dieth5laniino-l,3-butadiene react rapidly with acrolein at room temperature. 

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]. 

Fig. 8.3 Diene HOMO-dienophile LUMO interaction of endo transition state for the reaction of cyclopen-tadiene with acrolein (a) and protonated acrolein (b)...

Nafion-H (144), a perfluorinated resin-sulfonic acid, is an efficient Bronsted-acid catalyst which has two advantages it requires only catalytic amounts since it forms reversible complexes, and it avoids the destruction and separation of the catalyst upon completion of the reaction [94], Thus in the presence of Nafion-H, 1,4-benzoquinone and isoprene give the Diels-Alder adduct in 80% yield at 25 °C, and 1,3-cyclohexadiene reacts with acrolein at 25 °C affording 88 % of cycloadduct after 40 h, while the uncatalyzed reactions give very low yields after boiling for 1 h or at 100 °C for 3.5 h respectively [95], Other examples are given in Table 4.24. In the acid-catalyzed reactions that use highly reactive dienes such as isoprene and 2,3-dimethylbutadiene, polymerization of alkenes usually occurs with Nafion-H, no polymerization was observed. 

Secondary orbital interactions (SOI) (Fig. 2) [5] between the non-reacting centers have been proposed to determine selectivities. For example, cyclopentadiene undergoes a cycloaddition reaction with acrolein 1 at 25 °C to give a norbomene derivative (Fig. 2a) [6]. The endo adduct (74.4%) was preferred over the exo adduct (25.6%). This endo selectivity has been interpreted in terms of the in-phase relation between the HOMO of the diene at the 2-position and the LUMO at the carbonyl carbon in the case of the endo approach (Fig. 2c). An unfavorable SOI (Fig. 2d) has also been reported for the cycloaddition of cyclopentadiene and acetylenic aldehyde 2 and its derivatives (Fig. 2b) [7-9]. The exo-TS has been proposed to be favored over the endo- IS. 

The reaction of allylcerium compounds with acrolein can be used for preparation of either (Z,Z)- or (Z,E)-1,4-dienes, equations (I) and (II). Thus the allylcerium compound generated at - 78° from 5 reacts with acrolein at the same temperature to form (Z)-6. However, if the allylcerium compound is allowed to warm to - 40° before addition to acrolein, (E)-6 is obtained in 60% yield. Similarly, the reaction of the homoallylic cerium compound from 7 with acrolein can be controlled to give either (Z,Z)- or (Z,E)-8 selectively. 

Two other applications of catalyst 364, i.e. in cycloaddition reactions of a-substituted acroleins with dienes 374 and 376, have been depicted in equations 110 and 111237. Cycloadducts 375 and 377 have been used as precursors in the syntheses of cassiol and gibberellic acid, respectively. The use of catalysts 364 and 369b in cycloadditions with acrolein resulted in low enantioselectivities with opposite face selectivities. 

Sharpless asymmetric dihydroxylation procedure was applied to the synthesis of the side chain of azinomycin A (equation 26)43. Horner-Emmons condensation of phospho-nate 36 with a /J-aziridine substituted acrolein afforded dehydroamino acid diene 37. Treatment of the diene with catalytic amounts of an osmium reagent and dihydroquini-dine (DHQD) p-chlorobenzoate resulted in asymmetric dihydroxylation, producing diol 38. Diol 38 was further converted to the naphthyl ester. 

This and other similar cycloadditions, however, when unactivated hydrocarbons without heteroatom substituents participate in Diels-Alder reaction, are rarely efficient, requiring forcing conditions (high temperature, high pressure, prolonged reaction time) and giving the addition product in low yield. Diels-Alder reactions work well if electron-poor dienophiles (a, p-un saturated carbonyl compounds, esters, nitriles, nitro compounds, etc.) react with electron-rich dienes. For example, compared to the reaction in Eq. (6.86), 1,3-butadiene reacts with acrolein at 100°C to give formy 1-3-cyclohexene in 100% yield. 

Reactions of vinyl halides with acrolein acetals and secondary amines lead to the formation of minor amounts of dienal acetals and major amounts of aminoenal acetals (equation 35).s3 The diene product retains the sterochemistry in the vinyl halide while the aminoenal acetal loses it through equilibration of the ir-allylpalladium intermediate. 

Examples with 2-vinylindoles are also found. Thus, the reaction of N-methyl-2-(2-methoxyvinyl)indole, as a cis-trans mixture, with acrylonitrile and ethyl and methyl acrylate gives the corresponding Diels-Alder compounds [83IJC(B)846]. With N-methyl-2-(2-nitrovinyl)indole as diene, similar reactions occur with methyl acrylate, acrylonitrile, and acrolein acetal but in these cases, the fully aromatic compounds were isolated. The cycloaddition reaction with acrolein acetal was nonregioselective and the isolated adducts had a CHO group, indicating that the acetal had been hydrolyzed (presumably during work-up). 

Chiral dienes have proved to be less popular in asymmetric Diels-Alder reactions than their chiral dienophile counterparts. This is primarily a result of the problem of designing a molecule that incorporates a chiral moiety, such as the formation of a chiral isoprenyl ether or vinyl ketene acetal.187-190 In addition, diastereoselectivities often are not high,54 191-199 as illustrated by the cycloaddition of the chiral butadiene 5 with acrolein (Scheme 26.4). Improved stereoselection is observed through the use of double asymmetric induction, although this is a somewhat wasteful protocol.35,54 177 200... 

The moderate Lewis acidity of ruthenium complexes was used to promote catalytic Diels-Alder reaction of dienes and acrolein derivatives [21-23]. The enantioselective Diels-Alder reaction of methacrolein with dienes was catalyzed with cationic ruthenium complexes containing an arene or cyclo-pentadienyl (Cp) ligand and a chiral ligand such as phosphinooxazoline, pyridyl-oxazoline, monoxidized 2,2 -bis(diphenylphosphino)-1, T-binaphthyl (BINPO)or l,2-bis[bis(pentafluorophenyl)phosphanyloxy]-l,2-diphenylethane (BIPHOP-F). The reaction gave the cycloadduct in high yields with excellent... 

Diels-Alder reactions of the type shown in Table 12.1, that is, Diels-Alder reactions between electron-poor dienophiles and electron-rich dienes, are referred to as Diels-Alder reactions with normal electron demand. The overwhelming majority of known Diels-Alder reactions exhibit such a normal electron demand. Typical dienophiles include acrolein, methyl vinyl ketone, acrylic acid esters, acrylonitrile, fumaric acid esters (fnms-butenedioic acid esters), maleic anhydride, and tetra-cyanoethene—all of which are acceptor-substituted alkenes. Typical dienes are cy-clopentadiene and acyclic 1,3-butadienes with alkyl-, aryl-, alkoxy-, and/or trimethyl-silyloxy substituents—all of which are dienes with a donor substituent. 

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 possibility that metallocenes might function as Lewis acids in Diels-Alder reactions was probed with ferrocenium hexafluorophosphate [184]. The answer is affirmative the cycloadditions studied include methacrolein, crotonaldehyde, and methyl vinyl ketone as dienophiles and butadienes and cyclopentadienes as diene components. Yields are in the range 60-80 % with reaction times of 3-36 h at 0 to 20 °C. Fair to good yields were also obtained in reactions of isoprene and cyclopentadiene with acrolein and methyl vinyl ketone in the presence of 1 % [Pd(PPh3)2(MeCN)2](BF4)2 (in CH2CI2, room temperature). Methyl acrylate resulted in low yields, and chiral modification with (5)-BINAP is reported to give the cycloadducts with modest enantioselectivity [164]. 

The same explanation can be used to rationalize the outcome of the reaction of isoprene (2-methyl-1,3-butadiene) with acrolein (2-propenal). In this case, though, because the diene is 2-substituted, Cldiene is nucleophilic and combines with C2dienophiie to give the observed product. 

More complex cases can also be handled correctly by A/(r) indeed the regio-selectivity of the DA reaction involving a diene with a hetereoatom such as sulphur, can also be predicted.47 The reaction of (E)-4-aminobut-3-ene-2-thione with acroleine produces 4-amino-3,4-dihydro-6methyl-2H-thiopyran-3-carbaldehyde (ADMTC)47. This is the ortho adduct, as can be seen in Figure 11. 

Scheme 18). The reaction starting with ionized 1,3-butadiene involves charge exchange prior to the formation of the covalent adduct. In contrast to the aforementioned cases, ionized 1,3-butadiene reacts with acrolein and methyl vinyl ketone as the ene component, and a, -unsaturated ketones react as dienes to yield 2-vinyl-2,3-dihydropyrans 4. 

In allylic oxidation, an olefin (usually propylene) is activated by the abstraction of a hydrogen a to the double bond to produce an allylic intermediate in the rate-determining step (Scheme 1). This intermediate can be intercepted by catalyst lattice oxygen to form acrolein or acrylic acid, lattice oxygen in the presence of ammonia to form acrylonitrile, HX to form an allyl-substituted olefin, or it can dimerize to form 1,5-hexadiene. If an olefin containing a jS-hydrogen is used, loss of H from the allylic intermediate occurs faster than O insertion, to form a diene with the same number of carbons. For example, butadiene is fonned from butene. 

The Diels-Alder reaction (diene synthesis) is the addition of compounds containing double or triple bonds (dienophiles) to the 1,4 positions of conjugated dienes with the formation of six-membered hydroaromatic rings. Hydrocarbons most often used in the reaction are 1,3-butadiene, cyclopentadiene, and isoprene, and dienophiles used include maleic anhydride, acrolein, and acrylic acid. The literature on this process is thoroughly reviewed by Alder (1), Kloetzel (59), Holmes (48), and Norton (82). 

Since the disclosures that the thermal dimerizations of acrolein and methyl vinyl ketone provide the 3,4-dihydro-2W-pyrans (1, 2) derived from 4Tr and 2Tr participation of the a,3-unsaturated carbonyl compound in a Diels-Alder reaction, an extensive series of related observations have been detailed. This work has been the subject of several comprehensive reviews including the Desimoni and Tacco-ni extensive tabular compilation of work through 1974. Consequently, the prior reviews should be consulted for thorough treatments of the mechanism, scope, and applications of the [4 + 2] cycloaddition reactions of a,3-unsaturated carbonyl compounds. The [4 -t- 2] cycloaddition reactions of l-oxa-l,3-buta-dienes with their 4 rr participation in the Diels-Alder reaction exhibit predictable regioselectivity with the preferential or exclusive formation of 2-substituted 3,4-dihydro-2W-pyrans (equation 1). The exceptions to the predicted regioselectivity that have been observed involve the poorly matched [4 + 2] cycloaddition reaction of an electron-deficient 1-oxa-1,3-butadiene with an electron-deficient dienophile, e.g. methyl crotonate or methacrolein. Rigorous or simplified theoretical treatments of the [4 + 2] cycloaddition reaction of 1-oxa-1,3-butadienes predict the preferential formation of 2-substituted 3,4-dihy-dro-2f/-pyrans and accommodate the preferred endo approach of the reactants in which the carbon-carbon bond formation is more advanced than carbon-oxygen bond formation, i.e. a concerted but nonsynchronous [4 -t- 2] cycloaddition reaction. ... 

The reaction of the simplest diene derived from a carbohydrate (Scheme 7) with acrolein leads to a total endo selectivity furthermore, water increases the facial discrimination. This might be interpreted by considering the hydrophobi-city of the two faces, the attack on the more hydrophobic face (anti to hydrophilic functions) being favored in water [56]. 

Diels-Alder condensation of diene 1i with acrolein and juglone, catalyzed by BF3-ether and B(0Ac 3 respectively led to adducts 12 and 13 ( ). For the ratio of the absorptions for the aldeTiydic protons at 69.65 and 9.20 of 82 18 represents the degree of asymmetric induction and assigns the 1R.2R configuration to the major product - an interpretation confirmed by correlation with the known lR,2R-2-hydroxymethylcyclohexanol. 

In the event/ treatment of (36) with HBr and then strong base gave (35) with two centres established- The diene (33), duly synthesised by a Wittig reaction, gave an 85 15 ratio of endo (37) to exo Diels-Alder adducts with acrolein (CH2=CH.CHO). All the addition was from underneath. 

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