Isoprene cycloaddition

Leonard et al. have used the major adduct from isoprene cycloaddition to a chloronitroso compound in an efficient total synthesis of the cell division stimulant c/j-zeatin [Eq. (13)]. ... 

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). 

A broad study of aluminum chloride-induced cycloadditions of cyclopente-nones, cyclohexenones and cycloheptenones with 1,3-butadiene (1), isoprene... 

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... 

Similarly a marked increase of regioselectivity has been shown in the catalyzed Diels-Alder reactions of the chiral bicyclic lactame 24 (Scheme 3.9) with a variety of dienes [27] (isoprene, mircene, (E,E)-L4-dimethylbutadiene, 2,3-di-methylbutadiene, 2-siloxybutadiene). The catalyzed reactions were more regio-selective and totally enJo-antz-diastereoselective anti with respect to the bridgehead methyl group). The results of the cycloadditions with isoprene and mircene are reported in Scheme 3.9. The cycloadducts have then been used to provide interesting fused carbocycles [28] with high enantiomeric purity as shown in Scheme 3.10. 

Supported Lewis acids are an interesting class of catalysts because of their operational simplicity, filterability and reusability. The polymer-bound iron Lewis-acid 53 (Figure 3.8) has been found [52] to be active in the cycloadditions of a, S-unsaturated aldehydes with several dienes. It has been prepared from (ri -vinylcyclopentadienyl)dicarbonylmethyliron which was copolymerized with divinylbenzene and then treated with trimethylsilyltriflate followed by THF. Some results of the Diels-Alder reactions of acrolein and crotonaldehyde with isoprene (2) and 2,3-dimethylbutadiene (4) are summarized in Equation 3.13. 

Chiral titanium- and scandium-based catalysts (61 and 62, Figure 3.11) were used to accelerate the cycloadditions of acyl-l,3-oxazolidin-2-ones 60 (Scheme 3.14) with butadiene, isoprene and cyclopentadiene. The cycloadditions... 

The ability of zeolites to control the regioselectivity of Diels-Alder reaction has been investigated for the cycloaddition of isoprene with various dienophiles [20bj. Some results are reported in Table 4.6. All the zeolites tested afforded high regioselectivity but the reaction yield was generally low and depended on the zeolite as well as on the dienophile. 

The thermal instability of 37 reduces its applicability with poorly reactive dienes such as vinylcyclohexene and its derivatives 38, unless high pressure (HP) is employed. Ultrasound is not only effective in promoting the cycloaddition of 37 with 38, but sometimes also improves the regioselectivity. Some data are illustrated in Table 4.8 and compared with cycloadditions in refluxing benzene and under high pressure. The reactions of 37 with reactive dienes such as cyclopentadiene and l-(trimethylsiloxy)-1,3-butadiene give a good yield of type D adducts under mild conditions, while with less reactive dienes, such as isoprene and butadiene, poor results are obtained. 

The use of Lewis acids (ZnU, BF3 Et20) in ionic liquids, tested in the cycloaddition of but-3-en-2-one with isoprene, increases both the rate and selectivity of the reaction. The ionic liquid remains catalytically active after the work-up and can be reused. 

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... 

In accord with the proposed mechanism, copyrolyses of la or lb with 2,3-dimethyl-1,3-butadiene (DMB) or isoprene lead to silacyclopentene derivatives via a formal [4+1] cycloaddition of the silylenes (Scheme 2). The simultaneous existence of the silaethenes 2a/2b and the resulting silylenes 4a/4b in the gas phase is proven by the formation of the corresponding 1,3-disilacyclobutanes (5) and - in case of isoprene as the quenching partner - of the two isomeric silacyclohexenes 7 (Scheme 2) [2]. 

The main products correspond in most cases to a formal [4+l]-cycloaddition. With butadiene, isoprene or a,/3-unsaturated ketones small amounts of a double bond isomer (a,/3 to Si) are observed. With a,/J-unsaturated amines the latter type of isomer is the main product. The nature of both isomers is consistent with a primary [2+l]-cycloaddition, preferably at a C=Y unit (Y = O, NR), followed by a ring-opening isomerization. 

Cycloaddition of unsymmetrical 1,3-dienes, such as isoprene 41b, proceeded regiospecifically to give only a single regioisomer 44 (see Equation (13) and Table 7). 

Table 7 Polar cycloadditions of 1 -benzothiopyrylium salts 43 with isoprene 41 b (Equation 13)...

Recently, much attention has been paid to hetero Diels-Alder reactions as powerful tools for the construction of heterocyclic compounds. For example, cycloaddition of 2,3-dimethylbuta-l,3-diene 41a with 1,2-thiazinylium salt 95, in acetonitrile at room temperature, resulted in the exclusive formation of product 76a resulting from cycloaddition across the C—S1 bond (see entry 1 in Table 15 and Equation 26) <1999TL1505>. Similarly, isoprene 41b and... 

Lactam sulfonium salts bearing a dihydrothiopyran skeleton with a sulfonio bridgehead have been synthesized. Tricyclic benzothiazinium salts 87 were prepared by [4+2+]-polar cycloaddition of a thionium intermediate 99, generated from the corresponding a-chloro sulfide 98, in the presence of silver perchlorate in moderate to good yields (see Equation (28) and Table 17) <1997J(P1)309>. Cycloaddition with isoprene 41b gave adducts 87b and 87c as a... 

Many Diels-Alder [4 + 2] cycloadditions show a powerful pressure-induced acceleration, which is often turned to good synthetic purpose as discussed in Section III.A.2. Table 1 illustrates the effect of pressure on the Diels-Alder reaction of isoprene with acrylonitrile as a representative example. This reaction is accelerated by a factor of 1650 by raising the pressure from 1 bar to 10 kbar28. 

Cycloadditions (253) of butenolides with isoprene afforded a 1 1 mixture of Diels-Alder regioisomers. The selectivity is increased by the use of aluminum trichloride as catalyst. Although the butenolides studied did not react with furan, even in the presence of catalysts, they reacted smoothly with cyclopentadiene. For example, reaction of (—)-angelica lactone (159a) with... 

Scheme 6.7S Prod ucts of the cycloadditions of 1 -oxa-2,3-cyclohexadiene (351), liberated from exo-6-bromo-endo-6-fluoro-2-oxabicyclo[3.1.0]-hexane (354), to styrenes, 1,3-butadiene, isoprene, 2,3-dimethyl-l, 3-butadiene,...

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