Olefins synthetic utility

The Jacobsen-Katsuki epoxidation reaction has found wide synthetic utility in both academia and industrial settings. As described previously, the majority of olefin classes, when conjugated, undergo Mn(salen)-catalyzed epoxidation in good enantioselectivity. In this section, more specific synthetic utilities are presented. 

The AE reaction has been applied to a large number of diverse allylic alcohols. Illustration of the synthetic utility of substrates with a primary alcohol is presented by substitution pattern on the olefin and will follow the format used in previous reviews by Sharpless but with more current examples. Epoxidation of substrates bearing a chiral secondary alcohol is presented in the context of a kinetic resolution or a match versus mismatch with the chiral ligand. Epoxidation of substrates bearing a tertiary alcohol is not presented, as this class of substrate reacts extremely slowly. 

Acetylenes have hijh synthetic utility, and hydrogenation of the triple bond occurs in many reaction sequences (7). Often the goal of this reduction is formation of the cis olefin, which usually can be achieved in very high yields (for an exception, see Ref. 10). Continued reduction gives the paraffin. Experimentally, both the relative and absolute rates of acetylene and olefin hydrogenation have been found to depend on the catalyst, substrate, solvent, reaction conditions, and hydrogen availability at the catalyst surface. Despite these complexities, high yields of desired product usually can be obtained without difficulty. 

Olefins have often been shown to be intermediates in the saturation of aromatics (6,29,35,37,48,49), but their formation, in varying amounts, lacks synthetic utility. In the presence of an acidic catalyst, the intermediate olefin can be trapped by alkylation. Phenylcyclohexane has been obtained in good yield from benzene by this technique (40). 

Isopropanol (2-propanol) is an important alcohol of great synthetic utility. It is the second-largest volume alcohol after methanol (1998 U.S. production was approximately 1.5 billion pounds) and it was the 49th ranked chemical. Isopropanol under the name isopropyl alcohol was the first industrial chemical synthesized from a petroleum-derived olefin (1920). 

The photocycloaddition of an aldehyde or ketone with an olefin to yield an oxetane was reported by Paterno and Chieffi in 1909. 58> Contemporary studies on the synthetic utility and mechanistic features were initiated nearly 50 years later by Biichi et al. 59) Two review articles summarizing synthetic aspects of Paterno-Biichi reactions have been published 6.12)) and mechanistic studies have been reviewed several times. 6,38,60-62) The reaction involves the addition to olefin of a photo-excited carbonyl moiety. This circumstance makes it advantageous to review this reaction before a discussion of olefin-olefin additions, because the solution photochemistry of carbonyl compounds is probably better understood than any other aspect of organic photochemistry. Many of the reactions of carbonyl compounds have been elucidated during studies of the important phenomena of energy transfer and photosensitization. 63-65)... 

Despite the successful reactions mentioned above, olefin metathesis utilizing titanocene-methylidene is not necessarily regarded as a useful synthetic tool. Indeed, the steric interaction between the substituent at the carbon a to titanium and the bulky cyclopentadienyl ligand disfavors the formation of the titanocene-alkylidene 15. Hence, cleavage of the titanacycle affords only titanocene-methylidene and the starting olefin (Scheme 14.9). 

The potential synthetic utility of titanium-based olefin metathesis and related reactions is evident from the extensive documentation outlined above. Titanium carbene complexes react with organic molecules possessing a carbon—carbon or carbon—oxygen double bond to produce, as metathesis products, a variety of acyclic and cyclic unsaturated compounds. Furthermore, the four-membered titanacydes formed by the reactions of the carbene complexes with alkynes or nitriles serve as useful reagents for the preparation of functionalized compounds. Since various types of titanium carbene complexes and their equivalents are now readily available, these reactions constitute convenient tools available to synthetic chemists. 

Watt and Drummond, were considered to be inert for C-C bond forming reactions. However, by the expedient of transmetallation to Cu, Ni, Zn, Li, and Al, methodologies for the stereoselective synthesis of olefins and dienes, as well as unusual heterocycles, aromatics and their ring-annulated products are now available which are beginning to make impact on material science, e. g. synthesis of pentacenes and polyphenylenes. Takahashi and Li provide evidence that, with further developments in transmetallation and handling the zirconacycles outside of the Schlenk tube techniques, synthetic utility will increase and new catalytic reactions will be developed. 

When furan or substituted furans were subjected to the classic oxidative coupling conditions [Pd(OAc)2 in refluxing HOAc], 2,2 -bifuran was the major product, whereas 2,3 -bifuran was a minor product [12,13]. Similar results were observed for the arylation of furans using Pd(OAc)2 [14]. The oxidative couplings of furan or benzo[i]furan with olefins also suffered from inefficiency [15]. These reactions consume at least one equivalent of palladium acetate, and therefore have limited synthetic utility. 

Generally, the intermolecular Heck reaction between 2-iodo-, 4-iodo- and 5-iodo-l-methylimidazoles and olefins suffers from low yields (< 25%). Therefore, these transformations are of limited synthetic utility [29]. In one case, variable yields for adduct 62 (15-58%) were observed for the Heck reaction of 5-bromo-l-methyl-2-phenylthio-lf/-imidazole (61) and a large excess of methyl acrylate [42]. 

Valentine and Curtis (1975) extended the synthetic utility of potassium peroxide by reporting the successful solubilization of K02 in dry dimethyl sulfoxide using dicyclohexyl- 18-crown-6 ([20] + [21]). Corey et al. (1975) used 18-crown-6 to solubilize KOz in dimethylformamide, dimethoxyethane and diethyl ether, whilst Johnson and Nidy (1975) reported its solubilization in benzene. A wide variety of chemical transformations have been realized with K02 complexes of crown ethers. With alkyl halides the main reaction products are peroxides, alcohols and olefins (Johnson and Nidy, 1975). Peroxides are... 

The addition of selenenyl derivatives to olefins has been shown to be of mechanistic interest and synthetic utility because of the versatility of the selenium functionalities28,133. The possibility of modifying double bonds with seleno derivatives has been applied also to conjugated systems in order to obtain arylseleno dienes, or electron-deficient dienes, both being useful synthetic intermediates or building blocks. 

Phenol esters of a,(3-unsaturated carboxylic acids have an interesting reactivity due to the synthetic utility of the resulting hydroxychalcones (Scheme 19). This aspect will be illustrated in Section IV. However, from the basic point of view, it is worth mentioning that the cis or trans configuration of the olefinic part of the acyl moiety can have a marked influence on the photochemical reactivity of the ester. When para-methoxyphenyl fumarates are irradiated, the normal ortho-rearranged products are obtained. By contrast, irradiation of para-me-thoxyphenyl maleates does not lead to rearrangement. Instead, cyclization products are obtained (Scheme 20). 

Asymmetric catalytic hydrogenation is unquestionably one of the most significant transformations for academic and industrial-scale synthesis. The development of tunable chiral phosphorous ligands, and of their ability to control enantioselectivity and reactivity, has allowed asymmetric catalytic hydrogenation to become a reaction of unparalleled versatility and synthetic utility. This is exemplified in the ability to prepare en-antiomerically enriched intermediates from prochiral olefins, ketones, and imines through asymmetric hydrogenation, which has been exploited in industry for the synthesis of enantiomerically enriched drugs and fine chemicals. 

Although most of the photocycloaddition reactions have involved olefins, there are several examples of additions to other types of un-saturated systems (e.g., allenes, acetylenes, ketenimines, etc.) which extend their synthetic utility. It is impossible, at this time, to define the limitations of the reaction as applied to other systems however, this will unquestionably be an active and fruitful area of research in the future. 

The photochemical nucleophile olefin combination, aromatic substitution (photo-NOCAS) reaction, formulated below for 2,3-dimethylbutene-methanol-p-dicyano-benzene, has some synthetic utility. The final step, loss of cyanide ion, is not shown. 

However, from the outset of this field, the limitations as well as the potentials of this cycloaddition were also apparent. For instance, the efficiency of this cycloaddition in an intermolecular manner was typically low unless strained olefins were used. Moreover, the use of unsymmetrical alkenes led to a mixture of the cyclopentenone regioisomers. Synthetic utility of this reaction is considerably expanded by the emergency of the intramolecular reaction. Schore introduced the first intramolecular version forming several rings simultaneously, which is now the most popular synthetic strategy in natural product synthesis because of its conceptual and operational simplicity. Additionally, the regiochemistry is no longer the problem in this variation. 

It is clear from the enormous range of chemistries we have attempted to chronicle that research on catalytic transformations of the heavier Group 14 elements has been intense since the mid-1980s. Some reactions, such as double additions to olefins, previously known as curiosities have now been developed to a point where they possess significant synthetic utility to the nonspecialist chemist. Others have allowed ready access to new classes of polymers and materials. Substantial progress has also been made in... 

This early example is one of the numerous synthetic utilizations of the cycloadditions of olefins activated by sulfur atoms at various oxidation levels (vinyl sulfides, sulfoxides and sulfones = -S(0) R, n = 0,1, 2). Most of the work carried out in this field has been pertinently reviewed and discussed in a 1988 Tetrahedron Report with 204 references [485], Some specific aspects are underlined here and recent examples given. 

The discovery of an easy route to a series of l-chloro-l-(trichlorovinyl)cyclopropanes from the thermal reaction of tetrachlorocyclopropene and olefins greatly promoted the availability and synthetic utility of alkynylcyclopropanes. Upon reductive elimination with two equivalents of n-BuLi in ether-hexane at -78 °C, a series of ring substituted... 

Cycloaddition Reactions. The synthetic utility of the (2+2) photochemical cycloaddition of olefins to form cyclobutanes, eq. 9,... 

In the reactions with mono- and 1,2-disubstituted olefins, however, no ene product was obtained. This limitation has been overcome by the use of vinylic sulfides and selenides instead of mono- and 1,2-disubstituted olefins. With these substrates, the ene products are obtained with comparably high enantioselectivity and high diastereoselectivity [15]. The synthetic utility of the vinylic sulfide and selenide is shown in the synthesis of enantiopure (R)-(-)-ipsdienol, an insect-aggregation pheromone (Scheme 8C.4) [16]. 

Palladium acetate triarylphosphine complexes catalyze the addition of vinylic groups from vinylic halides to olefinic compounds in the presence of amines. Conjugated dienes are major products from 0,/3-unsaturated acids, esters, or nitriles while unactivated olefinic compounds react best in the presence of secondary amines where allylic amines are major products. The reactions are usually regio- and stereospecific. The synthetic utility of the reaction is illustrated with a wide variety of examples. 

In some cases the nucleophilic capture of a radical cation is followed by coupling with the radical anion (or possibly with the neutral acceptor), resulting ultimately in an aromatic substitution reaction. Thus, irradiation of 1,4-dicyanobenzene in acetonitrile-methanol (3 1) solution containing 2,3-dimethylbutene or several other olefins leads to capture of the olefin radical cation by methanol, followed by coupling of the resulting radical with the sensitizer radical anion. Loss of cyanide ion completes the net substitution reaction [144]. This photochemical nucleophile olefin combination, aromatic substitution (photo-NOCAS) reaction has shown synthetic utility (in spite of its awkward acronym). 

The unselective 6jt-electrocyclization can be avoided with substrates that lack a [3-olefin substituent (Scheme 7.41).116 When chiral, nonracemic versions of these substrates are employed, Woerpel and Calad demonstrated that the cascade reaction efficiently transfers the chiral information. While silver salts were competent catalysts for the diastereoselective formation of silalactone 144 from 1301, on scale-up, copper(II) triflate proved to be more efficient. The authors attribute the poorer performance by silver to product inhibition. In eight steps, silalactone 144 was transformed into the antibiotic (+ Hyu-acetomycin, to further highlight the synthetic utility of the cascade process. 

Further studies have shown that, to obtain an efficient amination, it is necessary to take into account both the difference in oxidation potential between the photocatalysts and the substrates and the positive charge distribution in the cation radicals of the olefin. The synthetic utility of the method was proven by the successful preparation of an aminotetraline, itself an intermediate for the synthesis of a compound with biological activities such as 2-aminoindan (26, Scheme 3.16b) [39]. As with the last synthesis, the redox-photosensitized amination occurred with no need for acids or bases, as usually required when using general protocols. 

Mechanistically, it was suggested [92] that this cyclization does not involve the free a-amino radical formed by cleavage of the C—Si bond of the trimethylsilylmethyl-amine radical cation. Instead, it was pointed out that cleavage of the C—Si a-bond from the delocalized trimethylsilylmethylamine radical cation, produced by a vertical overlap of the C—Si bond and empty p-orbital of nitrogen, is assisted by the 71-orbitals of the olefin. This strategy was applied to the stereoselective synthesis of pyrrolizidine and indolizidine ring systems [93]. The synthetic utility of this reaction is also demonstrated by the synthesis of ( )-iso-retronecanol [94]. 

Hydrogenation of the carbon-carbon triple bonds, particularly to the olefinic bonds, has been the subject of numerous investigations since the very early stage of the study on catalytic hydrogenation, not only in terms of its synthetic utility but also with respect to the selectivity of catalytic metals for the semihydrogenation.1-6... 

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