Isoprene 4 + 3 cycloaddition reactions

The reaction of dihalocarbenes with isoprene yields exclusively the 1,2- (or 3,4-) addition product, eg, dichlorocarbene CI2C and isoprene react to give l,l-dichloro-2-methyl-2-vinylcyclopropane (63). The evidence for the presence of any 1,4 or much 3,4 addition is inconclusive (64). The cycloaddition reaction of l,l-dichloro-2,2-difluoroethylene to isoprene yields 1,2- and 3,4-cycloaddition products in a ratio of 5.4 1 (65). The main product is l,l-dichloro-2,2-difluoro-3-isopropenylcyclobutane, and the side product is l,l-dichloro-2,2-difluoro-3-methyl-3-vinylcyclobutane. When the dichlorocarbene is generated from CHCl plus aqueous base with a tertiary amine as a phase-transfer catalyst, the addition has a high selectivity that increases (for a series of diolefins) with a decrease in activity (66) (see Catalysis, phase-TRANSFEr). For isoprene, both mono-(l,2-) and diadducts (1,2- and 3,4-) could be obtained in various ratios depending on which amine is used. 

The interest in chiral titanium(IV) complexes as catalysts for reactions of carbonyl compounds has, e.g., been the application of BINOL-titanium(IV) complexes for ene reactions [8, 19]. In the field of catalytic enantioselective cycloaddition reactions, methyl glyoxylate 4b reacts with isoprene 5b catalyzed by BINOL-TiX2 20 to give the cycloaddition product 6c and the ene product 7b in 1 4 ratio enantio-selectivity is excellent - 97% ee for the cycloaddition product (Scheme 4.19) [28]. 

It has been established that alkoxy alkenylcarbene complexes participate as dienophiles in Diels-Alder reactions not only with higher rates but also with better regio- and stereoselectivities than the corresponding esters [95]. This is clearly illustrated in Scheme 51 for the reactions of an unsubstituted vinyl complex with isoprene. This complex reacts to completion at 25 °C in 3 h whereas the cycloaddition reaction of methyl acrylate with isoprene requires 7 months at the same temperature. The rate enhancement observed for this complex is comparable to that for the corresponding aluminium chloride-catalysed reactions of methyl acrylate and isoprene (Scheme 51). 

It was also well established that silenes could take part as the dienophile in Diels-Alder reactions. In many cases, particularly with unsymmetric dienes such as isoprene, the reactions were not clean because, in addition to formation of the [2+4] cycloadduct 61, the possibility exists for the formation of it regioisomer 62, products of an ene reaction 63, and conceivably the [2+2] cycloaddition product 64, as shown in Eq. (23). Wiberg... 

Cycloaddition and ene reactions. Dienes >C=C—C=C< such as buta-1,3-diene, isoprene, 2,3-dimethylbuta-l,3-diene, fraws-piperylene, cyclopentadiene or anthracene react with 92 in Diels-Alder fashion to give [2 + 4] cycloadducts 410 (equation 128)62. Ene products 411 are formed additionally when the relative reaction rates for the [2 + 4] cycloaddition reaction and the ene reaction are comparable (e.g. for isoprene and 2,3-dimethyl-l,3-butadiene) Alkenes with allylic hydrogen (propene, 2-butene, isobutene) give ene products see equation 129. 

While studies of reactions in supercritical fluids abound, only a few researchers have addressed the fundamental molecular effects that the supercritical fluid solvent has on the reactants and products that can enhance or depress reaction rates. A few measurements of reaction rate constants as a function of pressure do exist. For instance, Paulaitis and Alexander (1987) studied the Diels Alder cycloaddition reaction between maleic anhydride and isoprene in SCF CO2. They observed bimolecular rate constants that increased with increasing pressure above the critical point and finally at high pressures approached the rates observed in high pressure liquid solutions. Johnston and Haynes (1987) found the same trends in the... 

Cycloaddition reactions of levoglucosenone (2) have been widely investigated and include the Diels-Alder reaction with various dienes such as cyclopentadiene, butadiene, and isoprene.11-14 In addition, 1,3-dipolar cycloadditions have been investigated.15... 

Glycosyl imines are not very reactive dienophiles in [4 + 2] cycloaddition reactions. However, they can be subjected to cycloaddition reactions after activation with Lewis acids [51]. TV-Galactosyl imines 7 were shown to react with isoprene in the presence of zinc(II) chloride to give the corresponding 4-methyl piperidine derivatives 43 (Scheme 25). 

The Diels-Alder cycloaddition reaction of maleic anhydride with isoprene has been studied in supercritical-fluid CO2 under conditions near the critical point of CO2 [759]. The rate constants obtained for supercritical-fluid CO2 as solvent at 35 °C and high pressures (>200 bar) are similar to those obtained using normal liquid ethyl acetate as the solvent. However, at 35 °C and pressures approaching the critical pressure of CO2 (7.4 MPa), the effect of pressure on the rate constant becomes substantial. Obviously, AV takes on large negative values at temperatures and pressures near the critical point of CO2. Thus, pressure can be used to manipulate reaction rates in supercritical solvents under near-critical conditions. This effect of pressure on reacting systems in sc-fluids appears to be unique. A discussion of fundamental aspects of reaction kinetics under near-critical reaction conditions within the framework of transition-state theory can be found in reference [759],... 

The cycloaddition reactions between 2- and 3-nitrofurans with isoprene,... 

Thermal cycloaddition reactions of benzo[c]cinnoline with butadiene and isoprene are reported to give only small yields of adducts in various solvents. Reactions of 1 and its 3,8-dimethyl derivative with dimethyl acetylenedicarboxylate at room temperature give the 1 2 adducts 56 and 57 via a stepwise process involving dipolar intermediates (see also Sections IV,A and 2.132 corresponding reactions of the diethyl ester in... 

The heterocyclic double bond in simple indoles will take part in cycloaddition reactions with dipolar 4n components,and with electron-deficient dienes (i.e. inverse electron demand), in most reported cases, held close nsing a tetherf° a comparable effect is seen in the intermolecular cycloaddition of 2,3-cycloalkyl-indoles to ortfto-quinone generating a l,4-dioxane. ° The introduction of electron-withdrawing substituents enhances the tendency for cycloaddition to electron-rich dienes 3-acetyl-1-phenylsulfonylin-dole, for example, undergoes aluminium-chloride-catalysed cycloaddition with isoprene, " and 3-nitro-l-phenylsulfonylindole reacts with l-acylamino-buta-l,3-dienes without the need for a catalyst. Both 3- and 2-nitro-l-phenylsulfonyl-indoles undergo dipolar cycloadditions with azomethine ylides. ... 

A certain number of well-known reactions in this series have been reinvestigated. Sasaki et al. have discussed the Diels-Alder 1,4-cycloaddition reactions of myrcene (27), comparing its activity with other dienes, in particular isoprene. ... 

Highly selective Diels-Alder reactions with other chiral auxiliaries attached to the dienophile have been documented. For example, chiral 2-oxazolidinones or the camphor sultam auxiliaries have proven particularly useful. Such cycloaddition reactions, catalysed by an alkylaluminium chloride, occur with a variety of dienes to give adducts in high yield and with very high diastereoselectivity. In many cases these adducts can be obtained diastereomerically pure by crystallization. The reactions are thought to occur by way of complexed ion pairs (e.g. 129), in which the substituent on the auxiliary shields one face of the dienophile from attack by the diene. For example, 2-methylbutadiene (isoprene) gave the adduct 127, which was converted into (i )-(+)-a-terpineol 128 (3.92). ... 

In thermal cycloaddition reactions of acrylates (type A, table column 3) only moderate endo/exo selectivities and diastereoselectivities have been observed.Mixtures of regioisomers have often been obtained with isoprene as the diene component. Reactions of chiral fumarates (B) derived fi-om (S)-lactate 15 with a variety of dienes (table column 4) lead to moderate to high selectivities. 

It is concluded from the results of the cycloaddition reactions of isoprene with the N-galactosyl imines 16, that the application of more electron-rich dienes should allow the reaction to be conducted at lower temperature and with higher stereoselectivity. In this sense, the N-galactosyl-imines 16 are reacted with l-methoxy-3-trimethylsilyloxybutadiene 19 (32) to give the N-galactosyl 2,3-dehydropiperidin-4-one derivatives 20 formed by subsequent elimination of methanol from the assumed cycloaddition products (33). 

Compound (1), prepared from selenium oxychloride (9) and yV,yV-bis(trimethylsilyl)toluenesulfonamide (10) (eq 7), has been isolated and utilized in [4 + 2] cycloaddition reactions with dienes. For example (1) reacts regioselectively with isoprene to yield 3,6-dihydro-1,2-selenazine (11) (eq 8). ... 

When la was heated with the less reactive isoprene 5 in a sealed ampoule at 150-200°C for 72 h using benzene as solvent, it showed its dienophilic character taking part in the DA cycloaddition reactions. The reactions proceeded to produce the mixture of isomeric benzofurans 10a and 10b as the principal products and dihydrobenzofurans 9a and 9b (global yield 62%) (Della Rosa, et al, 2005). (Figure 2) In the same manner, in the case of 1-tosyl-2-nitropyrrole 2a, it reacted with isoprene furnishing dihydroindole isomers lla,b and... 

Other optically active alcohols have been employed as auxiliaries in diastereoselective, auxiliary-controlled Diels-Alder cycloaddition reactions. Helm-chen has pioneered the use of pantolactone as a chiral auxiliary that has the ability to form chelates with appropriate Lewis acids [64, 65]. Thus, treatment of 106 with isoprene and TiCl4 furnished 108 as a 97 3 mixture of dia-stereomers (Equation 8) [65]. The Ti chelate 107 was proposed as a key intermediate, leading to superb levels of asymmetric induction in the cycloaddition. 

Highly uMtr-diastereofacial selective cycloaddition of isoprene (2) with 4-isopropyl-2-cyclohexenone allowed a short regiocontrolled and stereocon-trolled synthesis [13] of jS-cadinene and (y2-cadinene, Scheme 3.3). High anti-diastereofacial selectivity also occurs in the Diels-Alder reaction of optically active cyclohexenones 6-9 (Figure 3.2), readily available from the chiral pool, with open chain dienes [14-16]. Their cycloadducts are valuable intermediates in the synthesis of optically active sesquiterpenes in view of the easy conversion of the gem-dimethylcyclopropane and gem-dimethylcyclobutane in a variety of substituents. 

The presence of two substituents at C-4 also strongly influences the regios-electivity as shown in the cycloaddition of dienone 13 with isoprene (2) (Equation 3.1). In violation of the para-rule for Diels-Alder reaction, only metfl-adduct was obtained [19,20]. 

Strong effects of the catalyst on the regioselectivity have been observed in the cycloadditions of a variety of heterocyclic dienophiles. Some results of the BF3-catalyzed reactions of quinoline-5,8-dione (21) and isoquinoline-5,8-dione (22) with isoprene (2) and (E)-piperylene (3) [25], and of the cycloadditions of 4-quinolones (23a, 23b) as well as 4-benzothiopyranone (23c) with 2-piperidino-butadienes, are reported [26] in Scheme 3.8 and Equation 3.2. The most marked... 

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