C-H activation allylic

Trost and Toste51 isolated unexpected cycloheptene 69 upon exposing enyne 68 to their optimized ruthenium-based Alder-ene conditions (Equation (42)). Further exploration into the effects of quaternary substitution at the propargylic carbon revealed the ability of ruthenium to catalyze a non-Alder-ene cycloisomerization to form seven-membered rings, presumably via allylic C-H activation (Scheme 15). 

Asymmetric allylic C-H activation of cydohexadiene systems has been used for the asymmetric synthesis of several compounds of pharmaceutical relevance. The key step in the asymmetric syntheses of the monoamine reuptake inhibitor (-i-)-indatrahne 185 was the C-H insertion reaction of the aryldiazoacetate 183 with 1,4-cyclohexadiene (Scheme 14.24). The product 184, obtained in 83% yield with 93% enantiomeric excess, is readily converted to (-i-)-indatraline using standard synthetic procedures [132]. 

Asymmetric allylic C-H activation of more complex substrates reveals some intrinsic features of the Rh2(S-DOSP)4 donor/acceptor carbenoids [135, 136]. Cyclopropanation of trans-disubstituted or highly substituted alkenes is rarely observed, due to the steric demands of these carbenoids [16]. Therefore, the C-H activation pathway is inherently enhanced at substituted allylic sites and the bulky rhodium carbenoid discriminates between accessible secondary sites for diastereoselective C-H insertion. As a result, the asymmetric allylic C-H activation provides alternative methods for the preparation of chiral molecules traditionally derived from classic C-C bond-forming reactions such as the Michael reaction and the Claisen rearrangement [135, 136]. 

The asymmetric allylic C-H activation of cyclic and acyclic silyl enol ethers furnishes 1,5-dicarbonyl compounds and represents a surrogate of the Michael reaction [136]. When sufficient size discrimination is possible the C-H insertion is highly diastereoselective, as in the case of acyclic silyl enol ether 193 (Eq. 22). Reaction of aryldia-zoacetate 192 with 193 catalyzed by Rh2(S-DOSP)4 gives the C-H insertion product 194 (>90% de) in 84% enantiomeric excess. A second example is the reaction of the silyl enol ether 195 with 192 to form 196, a product that could not be formed from the usual Michael addition because the necessary enone would be in its tautomeric naphthol form (Eq. 23). 

The Claisen rearrangement of allyl vinyl ethers is a classic method for the stereoselective synthesis of y,J-unsaturated esters. The allylic C-H activation is an alternative way of generating the same products [135]. Reactions with silyl-substituted cyclohexenes 197 demonstrate how the diastereoselectivity in the formation of 198 improves (40% to 88% de) for the C-H insertion reactions as the size of the silyl group increases (TMS to TBDPS) (Tab. 14.14). Indeed, in cases where there is good size differentiation between the two substituents at a methylene site, high diastereo- and enantioselectivity is possible in the C-H activation. 

Tab. 14.14 Diastereocontrol achieved by size differentiation in allylic C—H activation.

Tab. 14.15 Kinetic resolution in allylic C-H activation of a-pinene and Rh2(S-DOSP)4.

An interesting aspect of the allylic C-H insertion is that the products are y,6-unsaturated esters. Traditionally, y,6-unsaturated esters are most commonly prepared by a Claisen rearrangement, especially if stereocontrol is required. Diastereocontrol is also possible in the C-H insertion as long as the reaction occurs at a methylene site where there is good size differentiation between the two substituents [21]. An example is the reaction between 17 and the silylcyclohex-ene 18 which forms the C-H insertion product 19 in 88% de and 97% ee [21]. Other catalysts such as Rh2(.R-BNP)4 and Rh2(S-MEPY)4 have been explored for allylic C-H activation of cyclohexene but none were was as effective as Rh2(S-DOSP)4 [22]. 

The divalent samarium complexes (CsMe5)2Sm and (C5Me5)2Sm(THF)2 have also been found to be effective precatalysts in these hydroamina-tion/cyclization reactions [68]. In this case the initial step is the formation of samarium(III) intermediates via allylic C-H activation [Eq. (15)]. 

Scheme 5. Allylic C-H activation via hydroboration of cyclic tetrasubstituted alkenes.

Scheme 11. Mechanism of stereoselective allylic C-H activation with tertiary alkylboranes.

In the presence of alkenes, palladium(II) salts form Pd(II)-olefin complexes. For olefins with allylic hydrogen atoms, these complexes undergo a rapid rearrangement to jr-allyl complexes by a process called allylic C-H activation [34], Nucleo-... 

Polymerization of propylene with complex 5 (Table 4) at atmospheric pressure produces an atactic polypropylene having the same features regarding the temperature and Al Zr ratio as for ethylene. The H and 13C-NMR spectroscopic analysis of polypropylene reveals only vinyl/isopropyl, but no vinylidene/n-propyl, end groups, similar to the polymers obtained with zirconocenes [67,68]. Polymers with these end groups may be formed from at least three different mechanisms. The first involves an allylic C-H activation of propylene, the second, a /1-methyl elimination, and the third, a /1-hydrogen elimination from a polymer chain in which the monomer inserts in a 2,1 fashion [69]. Since in the... 

This allylic C-H activation can be, in some specific cases, in competition with the direct transformation of monosubstituted enol ether into vinylic organometallic derivatives. Compound 116 reacts faster with 21 by the enol moiety to lead to 117 than with the remote double bond of 116, which would have given dienyl 118 after hydrolysis (Scheme 43). For the isomerization reaction to proceed, higher substitution of the enol ether is necessary. 

Therefore, the isomerization reaction was also performed starting from the a-substituted enol ether 119 (Scheme 52). By using the tandem allylic C-H activation-elimination reactions, Z-120c is initially formed and by a transmetalation reaction into organocopper with a stoichiometric amount of CuCI/ 2LiCl, followed by heating at +50 °C for 1 h and reaction with allyl chloride, the resulting ( , )-diene 122 is obtained with an isomeric ratio of 90 10 but in a low 40% yield as described in Scheme 52. 

Figure 26. Silver-catalyzed selective cyclopropanation over allylic C—H activation.

Scheme I 71-allylpalladium complexes from Pd-mediated Allyl C-H activation of alkenes...

Furthermore, Stahl and coworkers reported the oxidative amination of cyclic olefin (such as cyclopentene, cycloheptene) to afford cyclic allylic amine product. However, this reaction proceeds via m-am inopal I adation//i-hydride elimination pathway, rather than allylic C-H activation (Scheme 16) [33]. 

As noted throughout this section, substrates intended for allylic C-H activation are also capable of undergoing facile intermolecular cyclopropanation reactions. Both Davies [94] and Muller [45] have carried out systematic studies to determine the controlling factors that govern the selectivity between these two competing pathways (Scheme 24). 

Electrophilic, nitrenoid-mediated amination processes are often challenged to discriminate between alkene aziridination and C-H insertion in substrates possessing some degree of unsaturation. Alkene aziridination is typically favored owing to the greater nucleophilicity of an ordinary n bond vis-a-vis a ct-C-H center. White and coworkers have found an elegant solution to this difficult problem of chemo-selectivity with the advent of a selective Pd(II) catalyst for allylic C-H functionalization [138, 139]. In these examples, allylic C-H activation of terminal alkenes... 

The same group has reported the enantioselective electrophilic 7-amination of a,(3-unsaturated dinitriles and nitrile esters through allylic C-H activation with a cinchona alkaloid catalyst [56]. Thus (Scheme 11.15), the reaction of the corresponding unsaturated nitrile with diazo compound B0C2N2 in the presence of 10 mol% of catalyst 31 afforded the 7-aminated nitrile adducts in good yields (65-90%) and excellent enantioselectivity (86-99% ee). 

An oxidative cyclization of 4-alkenoic acids (37) has been developed. The reaction occurs in the presence of p-benzoquinone as oxidant and is believed to proceed via the TT-allyl Pd intermediate (38), generated by an allylic C—H activation. Moderate to good enantioselectivity was observed when the spiro bis(isoxazoline) ligand (SPRIX) (39) was employed. ... 

A recent example of isoxazolidine synthesis that involves generation of an allylpalladium complex via allylic C—H activation was reported by the White group [90]. As shown below (Eq. (1.52)), treatment of homoallylic carbamate 128 with Pd(OAc)2 in the presence of sulfoxide ligand 130 and phenylbenzoquinone (PhBQ) provided 129 in 72% yield with 6 1 dr. A related transformation that affords indohne products has been described by Larock [17a]. 

Scheme 12.97 Enantioselective Rh-catalyzed allylic C-H activation/addition to conjugated dienes [201].

The activation of non-activated C-H bonds is an important research field 14), In most cases, transition metal complexes have been used for this purpose 14-19). In this chapter, we wish to describe a stereoselective allylic C-H activation involving the thermal rearrangement of organoboranes (Scheme 7) 20-22). The observed stereochemistry may be best explained by a dehydroboration-rehydroboration mechanism, but mechanistic studies indicate that a more complex pathway involving a second molecule of BH3 may be involved. 

Activation of allylic C—H bonds for further functionalization via alkylation has been achieved (Scheme 3.18). Treatment of functionalized allyl benzenes with bis-sulflnylethane Pd(II) acetate as a catalyst facilitates an allylic C—H activation leading... 

Regioselective Acetoxylation via Allylic C H Activation typical Wacker/Wacker-type reactions... 

Oxidative Heck reactions via Pd(II) C—H functionalization of terminal alkenes with pinacol boranes have been described for the preparation of styrenes and derivatives through electrophilic Pd(II) catalysis (Scheme 3.20). ° Treatment of a functionalized allylic precursor with the Pd(II) catalysts listed facilitated an allylic C—H activation. Subsequent transmetallation of the aryl boronic acid and reductive elimination afforded the desired olefin with excellent stereoselectivity. The scope of the transformation allows for a variety of activating and deactivating substituents on the aryl boronic acid as well as numerous functional groups on the starting alkene. A tandem allylic C—H oxidation/vinylic arylation protocol has also been reported. " ... 

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