Alkenes intermolecular partners

The fadal diastereoselectivity of intermolecular cyclopentenone [2 + 2]-photocy-cloaddition reactions is predictable if the cyclopentenone or a cyclic alkene reaction partner is chiral. Addition occurs from the more accessible side, and good stereocontrol can be expected if the stereogenic center is located at the a-position to the double bond. In their total synthesis of ( )-kelsoene (11), Piers et al. [22] utilized cyclopentenone 9 in the [2 + 2]-photocycloaddition to ethylene (Scheme 6.5). The cyclobutane 10 was obtained as a single diastereoisomer. In a similar fashion, Mehta et al. have frequently employed the fact that an approach to diquinane-type cis-bicydo [3.3.0]octenones occurs from the more accessible convex face. Applications can be found in the syntheses of (+)-kelsoene [23], (—)-sulcatine G [24], and ( )-merri-lactone A [25]. 

Similarly to the situation shown for cyclic systems above [Eq. (45)], the presence of substituents capable of acting as ligands to cobalt on an acyclic olefln may be highly beneficial. The reaction shown in Eq. (49) is merely one of a large number of examples that ecplore the effects of the position, nature, and number of heteroatoms on the alkene reaction partner on the yield and regiochemistry of both the intermolecular and intramolecular Pauson-Khand reactions [93, 105, 111]. 

Scheme 4.18 With alkenes as intermolecular partners benzocyclobutene substructures are formed.

As mentioned at the beginning of this section, intermolecular [2 + 2] photocycloadditions quite often afford product mixtures, depending on the alkene used as a ground state partner. A complete overview of such reactions described in the last twenty years would be far beyond the scope of this section and therefore attention will be directed to examples where the symmetric substitution pattern of the alkene allows for the formation of a specific cyclobutane derivative. 

Intramolecular versions of the Heck reaction are very useful for the construction of ring systems. The entropic advantage of having both coupling partners present in the same molecule increases the efficiency of the insertion reaction and leads to efficient reactions. Moreover the intramolecular version can be carried out on hindered substituted alkenes, whereas the intermolecular Heck reaction is largely restricted to monosubstituted alkenes. These reactions illustrate the syn stereochemistry of both the insertion reaction and the elimination. A number of multicyclic natural products have been synthesized using intramolecular Heck reactions to assemble the skeletons, and this has become a powerful synthetic tool for such compounds. 

De Meijere and co-workers have extended the scope of this process by applying this palladium-mediated multicomponent reaction to the bicyclopropylidene 72 as the alkene partner (Scheme 8.33). In this case, the intermolecular trapping of 7r-allyl palladium intermediate 73 with a soft carbonucleophile or with primary or secondary amines affords only products 74 having a methylenecyclopropane end group [78],... 

Although the Heck reaction may be efficiently employed for synthesis, it has its limits that should not go unmentioned the Heck reaction can not—at least not intermolecularly—couple alkenyl triflates (-bromides, -iodides) or aryl triflates (-bromides, -iodides) with metal-free aromatic compounds in the same way as it is possible with the same substrates and metal-free alkenes. The reason is step 4 of the mechanism in Figure 16.35 (part II). If an aromatic compound instead of an alkene was the coupling partner the aromaticity with this carbopallada-tion of a C=C double bond would have to be sacrificed in step 4. Typically, Heck reactions can only be run at a temperature of 100 °C even if they proceed without any such energetic effort. This is why this additional energetically demanding loss of aromaticity is not feasible. 

The [3 + 2] photocycloaddition (Scheme 6.79) usually involves the ground-state alkene and the Si excited state of an electron-donor substituted benzene derivative, often via an exciplex intermediate.807,809 811,816 The discrimination between the ortho- and metacycloaddition pathways is dependent on the electron donor acceptor properties of the reaction partners and the position and character of the reactants substituents.807 The reaction typically produces many regio- and stereoisomers however, a suitable structure modification can reduce their number. Intermolecular and intramolecular versions of the reaction are presented in Scheme 6.88 (a) photolysis of the mixture of anisole and 1,3-dioxole (226) leads to the formation of two stereoisomers, exo- and endo-221, in mediocre ( 50%) chemical yields 830 (b) four different isomers are obtained in the intramolecular photocycloaddition of an anisole derivative 228. 831... 

The first report of a catalytic intermolecular cyclization was made by Pauson and Khand in 1974 [22], but the scope was limited to gaseous acetylene as the alkyne partner, strained olefins such as norbornene and norbornadiene as the alkene component, and TON s (turnover numbers) were modest (8-11). Several subsequent reports detailed the production of cyclopentenones from a substoi-chiometric amount of Co2(CO)g, but none were as efficient as Pauson s initial work [23,24]. Using ethylene as the alkene component, Rautenstrauch demonstrated the first efficient catalytic Pauson-Khand cyclization with a TON of 220, Eq. (5) [25]. A more general catalyst system employing (indenyl)Co(cod) was recently reported by Chung and Jeong, Eq. (6) [26]. The reaction was quite effec-... 

Unlike the parent ene reaction, where both the ene and eneophile are alkenes, in this modification the reacting partners are clearly differentiated. Furthermore, the carbonyl group is activated as an eneophile in the presence of Lewis acids and virtually all useful examples of both relative and absolute stereochemical control are effected in this fashion. Nonetheless, the intermolecular variant is generally only practical when the carbonyl group has special features that both enhance its reactivity, typically by introducing a functionality that destabilizes the partial positive charge on the carbonyl carbon, and limit or prevent alternative processes such as aldol reactions. 

The ene reaction involves an alkene fragment (the ene) that removes a hydrogen from an allylic fragment, with formation of a new carbon bond, as in 666.. s with the other reactions in this chapter, reactivity and stereochemistry in the ene reaction can be explained by frontier orbital theory. The reaction proceeds via interaction of the HOMO of the alkene (ene) and the LUMO of the allylic partner (enophile), illustrated by 667 in Figure 11.23." The intermolecular reaction usually requires very high temperatures (typically 250-... 

Intermolecular and intramolecular [3+2] cycloaddition reactions are among the most efficient and tvidely used procedures for synthesis of five-membered heterocycles. The reactive partners in these reactions are 1,3-dipoles and dipolarophiles such as alkenes and alkynes. 1,3-Dipoles vary in stability some can be isolated and stored, others are relatively stable, but they are usually employed immediately. Others are so unstable that they have to be generated and reacted in situ. There are tv ro general classes of dipole, often referred to as sp (Fig. 11.1) and sp -hybridized dipoles (Fig. 11.2). 

Alkenes also could be intermolecular reaction partners of the diynes 29, and thus benzocyclobutenes were formed [46]. Two important observations were made in this context ... 

Wender s group has also developed rhodium-catalyzed intermolecular [5-1-2] cycloadditions. At first, they found the catalysis system of Rh(PPh3)3Cl for the intramolecular reactions was not effective at all for the intermolecular reactions. To effect the intermolecular [5-1-2] cycloadditions, [Rh(CO)2Cl]2 must be used and oxygen substitution of the cyclopropane was necessary (see (17)) [37-39]. Then they successfully expanded the substrate to unactivated vinylcyclopropanes by adjusting the substituents. For monosubstituted alkynes, the substitution on the olefin terminus directs the formation of single isomer that minimized steric hindrance (see (18)) [40]. The [5-1-2] cycloadditions can also be applied to VCPs with allenes (see (19)) [41]. It should be noted that the alkyne substituent did not interfere with the reaction, indicating that allenes as reaction partners were superior to alkyne in the [5-1-2] cycloadditions. Curiously, the authors didn t report the corresponding intermolecular [5-1-2] cycloadditions of VCPs with alkenes. 

In a related way, the first intermolecular NHC-catalysed hydroacylation of unstrained alkenes (i.e., styrenes) has been reported. Using the triazolium salt (127) bearing an original 2,6-dimethoxyphenyl moiety, hydroacylation products have been obtained in good to excellent yields and with good to excellent levels of regioselectivity, the ratio (128) (129) (linear vs branched isomers) depending on the electronic nature of the styrene partner. 

Even though not strictly speaking belonging to enyne cycloisomerization, an alkyne and an alkene can react intermolecularly with each other provided the alkyne is properly activated. Zhang and co-workers reported a number of such cycloadditions where a gold-mediated cascade was initiated by carbonyl addition to the alkyne moiety. The resulting 1,4- or 1,3-dipoles could then participate to formal [4 + 2] and [3 + 2] cycloadditions with an olefinic partner, giving access to... 

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