Isoprene cycloaddition with

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. 

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. 

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. 

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... 

A large number of metal-coordinated chalcogenacycles were prepared from the heteroaldehyde and -ketone complexes [M(CO)5 E=C(Ph)R ] (M = Cr, Mo, W E = S, Se, Te R = H, Aryl) and 1,3-dienes. The cycloadditions proceeded rapidly, even at low temperatures.179180,228-233 As dienes 2,3-dimethyl-l,3-butadiene [for an example see Eq. (27)], isoprene, transA, 3-pentadiene, cyclopentadiene, pentamethylcyclopentadiene, and 1,3-cyclohexadiene were used. Decomplexation with pyridine/THF yielded the free heterocycles. Although the tellurobenzaldehyde complex [W(CO)5 Te = C(Ph)H ] (99c) proved too unstable for isolation, it could be generated and employed in subsequent cycloadditions with dienes.180... 

There are a few reports in the literature in which the carbonyl group has been formally replaced by another unsaturated function. Thio-benzophenone (268) undergoes photochemical 1,2-cycloaddition to a-phellandrene (269) to give the thietane (270), together with the sulfur heterocycles (271 and 272) formed by 1,4-cycloaddition.298 Isoprene, cyclopentadiene, and 1,4-diphenylbutadiene also undergo 1,4-cycloaddition with thiobenzophenone, but 1,3-cyclooctadiene... 

EtO)PS ) give 3-0- or 3-S- substituted thietanes, respectively. Thiirane structures reported as the products of several reactions have been shown to be thietanes. The acrylate adducts undergo Diels-Alder cycloadditions with butadiene, isoprene, and cyclopentadiene. ... 

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. ... 

In 1987, Matsuda et al. reported the first Rh-catalyzed intermolecular [4+2] cycloaddition (Scheme 2-65). The cationic rhodium-complex-catalyzed codimerization of isoprene (491) with alkynes 390, affording the corresponding cyclohexadienes 492 in 44-85%, yields and excellent regioselectivity. 

The silyl (14) and stannyl (15) derivatives of isoprene undergo facile cycloaddition with a wide variety of dienophiles. When the latter are unsymmetrical there is a strong preference for formation of the "para" product (16). An improved synthesis of the useful prenylating agent (17) has been described. Reaction of isoprene (1) with sulphonyl chlorides gives a mixture of the... 

Diels-Alder Reactions. 2-Trimethylsilylmethyl-1,2-butadiene and 2-trimethylstannylmethyl-1,3-butadiene undergo facile cycloaddition with dienophiles (eq 11). The reactions of 2-trimethylsilylmethyl- and 2-trimethylstannylmethyl-1,3-butadiene with unsymmetrical dienophiles give the so-called para product predominantly, and the selectivity is much higher in the reactions with 2-trimethylsilylmethyl- and 2-trimethylstarmylmethyl-1,3-butadiene compared to reactions with isoprene. The paralmeta ratios in the reactions with methyl acrylate (eq 12) are 70/30 (X = H), 84/16 (X = SiMej), and 91/9 (X = SnMes)."... 

An exarr ile of a Diels-Alder cycloaddition with Al(OTf)3 has been disclosed. In solvent-free conditions, the cycloaddition of ethoxycarbonylcoumarrn with isoprene occurred in a 95% conversion. 

Cycloadditions with the acyclic diene, isoprene, proceeded much less efficiently. For example, zinc oxyallyl... 

Isoprene and 2,3-dimethyl-l,3-butadiene were also found to trap oxyallyl 37 in a [3-1-4]-cycloaddition to give bridged adducts 47 in 50% yield. These reactions are interesting in that most examples of [4-1-3]-cycloadditions with putative oxyallyl intermediates have used cyclic dienes. 

Narasaka advanced the use of chiral TADDOL-titanium complexes as catalysts for enantioselective Diels-Alder reactions [75-78], In order to minimize the conformational flexibility of the substrates, dienophiles 136 were employed because of their ability to participate in chelate formation with Lewis acids (Equation 15). In the presence of titanium catalyst 137 [76], isoprene (135) undergoes cycloaddition with 136 to give adduct 138 as one diastereomer in 96 % ee and 93 % yield [77]. 

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... 

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]. 

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