Olefin functionalization

Most rosin utilization takes advantage of the carboxyl and olefinic functionalities of the resin acids. 

The high chemoselectivity for the Baeyer-Villiger process was utilized in the synthetic elaboration of another hetero-bicyclic substrate. The biooxidation only provides the expected unsaturated lactone in a desymmetrization reaction without compromising the olefin functionality. The biotransformation product was then converted to pivotal intermediates for C-nucleosides like showdomycin, tetrahydro-furan natural products like kumausyne, and goniofufurone analogs in subsequent chemical operations (Scheme 9.17) [161]. 

Figure 57.28. The retention of olefin functionality (% IV) during the hydrogention of fatty nitriles to fatty amines over activated Ni with and without H2CO modification.

In parallel investigations, Danishefsky and coworkers accomplished the preparation of the 16-membered lactone of a model epothilone system via an alternative C9,C10 disconnection [14] (Scheme 4). In this case, coupling of epoxy-alcohol 17 with acids 18a and 18b afforded trienes 19a and 19b respectively. RCM of 19a under the influence of ruthenium initiator 3 produced dienes 20a as a 1 1 mixture of Z -isomers. Under identical conditions, cyclization of 19b produced a single product 20b (tentatively assigned as the Z-isomer). The variable stereoselectivity observed in these reactions was inconsequential since the olefinic functionality could be reduced to afford the corresponding saturated macrolactones. Schrock s molybdenum initiator 1 promoted the cyclization of 19a and 19b with similar efficacy [14]. 

Catalytic ring-closing metathesis makes available a wide range of cyclic alkenes, thus rendering a number of stereoselective olefin functionalizations practical. The availability of effective metathesis catalysts has also spawned the development of a variety of methods that prepare specially-outfitted diene substrates that can undergo catalytic ring closure. The new metathesis catalysts have already played a pivotal role in a number of enantioselective total syntheses. 

Considering an olefinic functionality as a chromophore, the absolute configuration of cyclic allylic alcohols can be determined using a method that involves the conversion of the alcohol to the corresponding benzoate.60 This can also be extended to acyclic alcohols where the conformations are dynamic (see Fig. 117). Interested readers may consult the literature for details.61... 

Allylic alcohol derivatives are quite useful in organic synthesis, so the asymmetric synthesis of such compounds via asymmetric hydrogenation of dienyl (especially enynyl) esters is desirable. The olefin functionality preserves diverse synthetic potential by either direct or remote functionalization. Boaz33 reported that enynyl ester and dienyl ester were preferred substrates for asymmetric hydrogenation using Rh-(Me-DuPhos) catalyst [Rh(I)-(R,R)-14], and products with extremely high enantioselectivity (>97%) were obtained (Schemes 6-11 and 6-12). 

Fixed beds are the main interest of this Section. Usually it is adequate to assume that the fluid and solid are at the same temperature at a point. There are cyclic processes, however, where the solid is first heated with flue gases or by burning off carbon before contacting the reacting fluid for a time. A moving bed of heated pebbles (Phillips pebble heater) has been used for the production of olefins from butane and for the fixation of atmospheric nitrogen. A fluidized sand cracker for the production of olefins functions similaiiy, with burning in a separate zone. 

The procedure described here allows for a convenient and efficient preparation in very high yields of large quantities of bromides from carboxylic acids containing an olefinic functionality. The Hunsdiecker reaction is traditionally accomplished by treating anhydrous silver carboxylates with bromine or iodine.2 Heavy metal salts such as mercury,3 lead,4 and thallium5 have also been used successfully as well as tert-butyl hypoiodite.6 The major disadvantages associated with the above methods, such as use of heavy metal salts and non-tolerance towards olefins, has led to the development of a more versatile method using O-acyl thiohydroxamates.7 8 The O-... 

Similarly, an intramolecular C—C bond formation was observed in the electrolysis of other phenols with olefinic functionality in the side chain [73-76]. 

Ring-closing metathesis seems particularly well suited to be combined with Passerini and Ugi reactions, due to the low reactivity of the needed additional olefin functions, which avoid any interference with the MCR reaction. However, some limitations are present. First of all, it is not easy to embed diversity into the two olefinic components, because this leads in most cases to chiral substrates whose obtainment in enantiomerically pure form may not be trivial. Second, some unsaturated substrates, such as enamines, acrolein and p,y-unsaturated aldehydes cannot be used as component for the IMCR, whereas a,p-unsaturated amides are not ideal for RCM processes. Finally, the introduction of the double bond into the isocyanide component is possible only if 9-membered or larger rings are to be synthesized (see below). The smallest ring that has been synthesized to date is the 6-membered one represented by dihydropyridones 167, obtained starting with allylamine and bute-noic acid [133] (Fig. 33). Note that, for the reasons explained earlier, compounds... 

Et3N unquestionably played an important role. In the presence of 0.5 molar equivalent of this amine, endoxide 55 was reduced by low-valent titanium reagent (molar ratio of endoxide TiCl LiAlH4 EtjN = 1 6.9 2.7 0.5) to a mixture of products, namely endo,cis-9S and trans-95 in a ratio of 1 5 (Scheme 20). In many cases, this reducing system would reduce enedicarboxylates to succinates, while other unactivated olefinic functionalities in the molecules would remain intact. A fitting example was the convCTsion of 96 to 97 as shown in Scheme 20. ... 

In principle, 9 is ideally suited for an abstraction of an anionic ligand to coordinate the pendant olefinic function or even additional proton abstraction altogether HCI elimination) to convert it into an allyl ligand (Eq. 6). However, so far, attempts to realise any kind of interaction were imsuccessful possibly the ligand chosen is not suited to bind to a Mo centre in a chelating allyl/imido or olefin/imido mode. 

The CM of olefins bearing electron-withdrawing functionalities, such as a,/ -unsaturated aldehydes, ketones, amides, and esters, allows for the direct installment of olefin functionality, which can either be retained or utilized as a synthetic handle for further elaboration. The poor nucleophilicity of electron-deficient olefins makes them challenging substrates for olefin CM. As a result, these substrates must generally be paired with more electron-rich crosspartners to proceed. In one of the initial reports in this area, Crowe and Goldberg found that acrylonitrile could participate in CM reactions with various terminal olefins using catalyst 1 (Equation (2))." Acrylonitrile was found not to be active in secondary metathesis isomerization, and no homodimer formation was observed, making it a type III olefin. In addition, as mentioned in Section 11.06.3.2, this reaction represents one of the few examples of Z-selectivity in CM. Subsequent to this report, ruthenium complexes 6 and 7a were also observed to function as competent catalysts for acrylonitrile... 

Thus changing the ligands on dirhodium(II) can provide a switch which, in some cases, can turn competitive transformations on or ofT146. Other examples include the use of dirhodium(II) carboxamides to promote cyclopropanation and suppress aromatic cycloaddition146. For example, catalytic decomposition of diazoketone 105 with dirhodium(II) caprolactamate [Rh2(cap)4] provides only cyclopropanation product 106. In contrast, dirhodium(II) perfluorobutyrate [Rh2(pfb)4] or dirhodium(II)triphenylacetate [Rh2(tpa)4] gave the aromatic cycloaddition product 107 exclusively (equation 100)l46 148. Although we have already seen that rhodium(II) acetate catalysed decomposition of diazoketone 59, which bears both aromatic and olefinic functionalities, afforded stable norcaradiene 60 (equation 70)105, the rhodium(II) acetate catalysed carbenoid transformation within an acyclic system (108) showed no chemoselectivity (equation 101). However, when dirhodi-um(II) carboxamides were employed as catalysts for this type of transformation, only cyclopropanation product 109 was obtained (equation 101). ... 

What is the reaction called that introduces the olefin functionality into compound 107 Is it a) an aldol reaction, b) an allylation c) an alkylation or d) a crotylation ... 

Success in the use of Ti tartrate catalyzed asymmetric epoxidation depends on the presence of the hydroxyl group of the allylic alcohol. The hydroxyl group enhances the rate of the reaction, thereby providing selective epoxidation of the allylic olefin in the presence of other olefins it also is essential for the achievement of asymmetric induction. The role played by the hydroxyl group in this reaction is described in a later section of this chapter. The need for a hydroxyl group necessarily limits the scope of this asymmetric epoxidation to a fraction of all olefins. Fortunately, allylic alcohols are easily introduced into synthetic intermediates and are very versatile in organic synthesis. The Ti tartrate catalyzed asymmetric epoxidation of allylic alcohols has been applied extensively as documented in the literature and in this review. The development of methods aimed at catalytic asymmetric epoxidation of unfunctionalized olefins is described in Chapter 6B, whereas the catalytic asymmetric dihydroxylation of olefins, which provides an alternate method for olefin functionalization, is described in Chapter 6D. 

The cis dihydroxylation of olefins mediated by osmium tetroxide represents an important general method for olefin functionalization [1,2]. For the purpose of introducing the subject of this chapter, it is useful to divide osmium tetroxide mediated cis dihydroxylations into four categories (1) the stoichiometric dihydroxylation of olefins, in which a stoichiometric equivalent of osmium tetroxide is used for an equivalent of olefin (2) the catalytic dihydroxylation of olefins, in which only a catalytic amount of osmium tetroxide is used relative to the amount of olefin in the reaction (3) the stoichiometric, asymmetric dihydroxylation of olefins, in which osmium tetroxide, an olefinic compound, and a chiral auxiliary are all used in equivalent or stoichiometric amounts and (4) the catalytic, asymmetric dihydroxylation of olefins. The last category is the focus of this chapter. Many features of the reaction are common to all four categories, and are outlined briefly in this introductory section. 

C-H functionalization, 10, 121 C-H intermolecular functionalization, 10, 122 C-H intramolecular functionalization, 10, 130 olefin functionalization, 10, 155 /)3-Carbon atoms, C-H bond functionalization activated alkyl groups intermolecularly, 10, 111 activated alkyl groups intramolecularly, 10, 114 alkanes and alkyl units, 10, 102 Carbon-based ligands, alkali metal chemistry, 2, 3 Carbon-based 77-ligands, in molybdenum carbonyls alkenes, 5, 433 alkynes, 5, 435 allenes, 5, 433... 

---