Allylic C-H bonds functionalization

Palladium-Catalyzed Allylic C-H Bond Functionalization of Olefins... 

Scheme 5.19 Chiral counteranion strategy for Pd-catalyzed asymmetric allylic C—H bond functionalization reported by Gong.

In fact, the stepwise nature of [Ru2(hp)4Cl] catalyzed reaction accounts for preferential allylic C-H bond functionalization over alkene aziridination which is the favored product when dirhodium catalysts are used. The presence of a discrete diradical intermediate further assists the selectivity for allylic C-H amination using a diruthenium catalyst. 

The C-H functionalization protocol is not limited to the development of surrogate chemistry to enolate transformations. The C-H activation at allylic C-H bonds readily generates 7,6-unsaturated esters, the products of the classic Claisen rearrangement (Figure 6). 

Imido selenium compounds Se(NR)2, where R = Bu or Ts, were first noted to give allylic amination of alkenes and alkynes.232 Formally the NR function is inserted into the allylic C—H bond yielding the C—NHR moiety. Related reactivity was also found for the sulfur imides, S(NR)2.233 Reactions between 1,3-dienes and Se(NTs)2 give [4 + 2] adducts which, in the presence of TsNH2, react to generate 1,2-disulfonamides.234... 

C-H Bond activation [ 1 ] and C-C bond formation are two of the key issues in organic synthesis. In principle, the ene reaction is one of the simplest ways forC-C bond formation, which converts readily available olefins into more functionalized products with activation of an allylic C-H bond and allylic transposition of the C=C bond. The ene reaction encompasses a vast number of variants in terms of the enophile used [2]. 

Under the same conditions, several types of hydrocarbon are also converted to fully deuterated compounds. The results are summarized in Table 1. Cydooctene was also transformed into fully deuterated cydooctene without a skeletal rearrangement. As shown in entries 2 and 3, saturated hydrocarbons have also been transformed into fully deuterated compounds. As described above, an interaction between allylic C-H bonds and palladium hydride induces the H-D exchange reaction for alkenes. H-D exchange in alkanes, however, cannot be explained in this way. Direct C-H activation without assistance from any functional group may be a route to the formation of fully deuterated alkanes. 

Li and coworkers [16] discovered that in the presence of RuCl2(PPh3)3, which is compatible with water and air, the allylic C-H bond was activated and the functional groups of homoallyl alcohols were repositioned to give allyl alcohols (Eq. 1). The experimental procedure is very simple stirring a mixture of homoallyl alcohol 1 with a catalytic amount of RuCl2(PPh3)3 in water and air at 90-100 °C for 1-3 h led to the product 2. 

The insertion reactions into cyclohexane C-H bonds (Table 1) give some idea of which nitrenes give synthetically useful yields. However, since most other substrates will contain more than one sort of C—H bond, it is important to know the selectivity of nitrenes for different types of C—bond. Several studies of nitrene selectivity towards tertiary, secondary and primary unactivated C—H bonds have been made, although attempts to study allylic C—H insertion reactions are complicated by the competing nitrene addition to the double bond. In cyclohexene it has been estimated Aat the allylic C—H bond is only about three times more reactive than the homoallylic C—H bond towards insertion of ethoxycarbo-nylnitrene. However, the reaction is totally unsatisfactory as a means of allylic functionalization since, as shown in Scheme 3, the yields are so low. 

The hydroxylation of allylic C-H bonds presents a serious challenge in synthetic organic chemistry, because a number of natural products contain substructures which can be approached synthetically via allylic functionalization moreover the allylic alcohol is in itself a very useful synthon, as demonstrated by the wide application of the Sharpless epoxidation2. 

Azo-ene reactions. The ene reaction provides a powerful method for C-C bond formation with concomitant activation of an allylic C-H bond. A variety of functionalized carbon skeletons can be constructed due to the range of enophiles which can be used. For example, carbonyl compounds give homoallylic alcohols and imino derivatives of aldehydes afford homoallylic amines. The azo-ene reaction offers a method for effecting allylic amination by treatment of an alkene with an azo-diester to afford a diacyl hydrazine which upon N-N cleavage furnishes a carbamate. Subsequent hydrolysis of the carbamate provides an allylic amine. Use of chiral diazenedicarboxylates provides a method for effecting stereoselective electrophilic amination. 

This mechanistic proposal in turn prompts the suggestion that the function of the superoxide dismutase proteins is to prevent free HOO- from coming into contact with allylic C-H bonds in the biological matrix. One approach is to minimize the lifetime of O2 -/HOO-, which is in addition to the radical-radical coupling proposition to deactivate HOO-. For a steady-state flux of 30 X 10 M O2 -/HOO- at pH 5 (1) without superoxide dismutase (SOD) the approximate half-life of O2 -/HOO- is about 30 ms... 

Keywords Palladium-catalyzed Allylic C-H bond activation Unactivated olefin 7t-allylpalladium Oxidative functionalization... 

Palladium Catalysts Palladium catalysts are effective and powerful for C—H bond functionalization. Carbene precursors and directing groups are commonly used strategies. Generally, sp3 C—H bond activation is more difficult than sp2 C—H bond activation due to instability of potential alkylpalladium intermediates. By choosing specific substrates, such as these with allylic C—H bonds, palladium catalytic systems have been successful. Both intramolecular and intermolecular allylic alkylation have been developed (Scheme 11.3) [18]. This methodology has presented another alternative way to achieve the traditional Tsuji-Trost reactions. 

Relative reactivities of olefins were determined by Adams (132) by feeding a mixture of the olefin to be tested with 1-butene. The rate of oxidation was found to be a strong function of the olefin structure, being inversely related to the strength of the allylic C—H bond. These results will be discussed in a later section. 

The C—H bond in 1,4-cyclohexadienone, Y(C6H6)=0 to Y(C6H5 )=0 + H, is 73.3 kcal mof which is even lower than the double allylic C—H bond in 1, 4 cyclohexadiene, which is 75 to 76 kcal-mof. The value from density functional analysis is lower at 69.7. We used G3 for this system, which yielded a value of 70.3 kcal mof. We recommend the G3 value for of... 

While silyl enol ethers 21 and 23 were subjected to similar reaction conditions (Tables 1.5 and 1.6), the allylic C—H bond could also be functionalized by metal carbenoids to afford silyl-protected 1,5-dicarbonyls 22 and 24 respectively, which can be viewed as an equivalent of an asymmetric Michael reaction. Although the double bond is highly electron-rich and readily undergoes cyclopropanation in the presence of most other metal carbenoids, by using aryldiazoacetates 1 as carbene precursors, cyclic silyl enol ethers 21 were readily transformed into their corresponding allylic C—H bond insertion products 22 (22 ) in excellent yields, excellent ee and moderate de (Table 1.5). Noticeably, while acyclic silyl enol ethers 23 were subjected to the reaction, excellent diastereoselectivity (>90% de) was obtained, which shows great potential in synthetic applications (Table 1.6). 

Intriguingly, while vinyldiazoacetates are utilized as carbene precursors in the allylic C—H bond insertion reaction catalyzed by Rh complexes, the combined C—H bond functionalization/Cope rearrangement occurs readily. This has emerged as a reliable methodology for the construction of 1,5-diene compounds bearing two vicinal stereogenic centers and will be discussed in detail in Section 1.1.2.6. 

Quite recently, Davies and co-workers developed a new class of sterically demanding dirhodium tetracarboxylate catalysts, especially Rh2(R-BPCR)4, that changed the site selectivity of the C(sp )—H bond insertion reaction. In the presence of catalytic amount of Rh2(R-BPCR)4, the primary C—H bond is the preferred reaction site of various substrates containing primary benzylic C—H bonds, allylic C—H bonds, or C—H bonds a to oxygen, which is complementary to Rh2(i -DOSP)4 which favors secondary C—H bonds (Scheme 1.17a-c). Moreover, the use of this methodology was further proved by the selective C—H bond functionalization of complex molecules such as (-)-a-cedrene (Scheme 1.17d). 

Pioneered by the seminal work of Lim and Kang on the alkylation of C—H bond using a rhodium catalyst, the chelation-assisted Rh-catalyzed C—H bond functionalization reactions for new C—C bond construction have witnessed significant improvements. Various aromatic, vinylic, and even allylic C—H bonds were found possible to be cleaved by a chiral Rh catalyst. The formed C—Rh species can readily react with common unsaturated functionalities such as alkenes, alkynes, allenes, and even ketones and imines. 

Scheme 5.44 Asymmetric cyclization of JV-allylic imidazoles via C—H bond functionalization reaction reported by Bergman and Ellman.

Another approach to create diverse C—H bond functionalization is to combine one C—H bond activation with a subsequent transformation which greatly enriches the diversity of the initial C—H bond functionalization products. Bearing this concept in mind, Sharma and Hartwig recently developed a one-pot process involving the linear selective Pd-catalyzed allylic C—H bond oxidation and subsequent enantioselective branched Ir-catalyzed allylic substitution to form products with new C—O, C—N, C—C, and C—S bonds (Scheme 5.67). The utility of this process was further demonstrated by an iterative sequence of C—H bond functionalization and homologations to prepare enantioenriched (l,n)-functionalized alkenes. 

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