Alkenes, internal, chemoselective

Stereoselective and chemoselective semihydrogenation of the internal alkyne 208 to the ew-alkene 210 is achieved by the Pd-catalyzed reaction of some hydride sources. Tetramethyldihydrosiloxane (TMDHS) (209) i.s used in the presence of AcOH[116]. (EtO)3SiH in aqueous THF is also effective for the reduction of alkynes to di-alkenes[l 17], Semihydrogenation to the d.v-alkene 211 is possible also with triethylammonium formate with Pd on carbon[118]. Good yields and high cis selectivity are obtained by catalysis with Pd2fdba)3-Bu3P[119],... 

Epoxides are regio- and stereoselectively transformed into fluorohydrins by silicon tetrafluoride m the presence of a Lewis base, such as diisopropyleth-ylamme and, m certain instances, water or tetrabutylammonium fluoride The reactions proceed under very mild conditions (0 to 20 C in 1,2-diohloroethane or diethyl ether) and are highly chemoselective alkenes, ethers, long-chain internal oxiranes, and carbon-silicon bonds remain intact The stereochemical outcome of the epoxide ring opening with silicon tetrafluoride depends on an additive used, without addition of water or a quaternary ammonium fluoride, as fluorohydrins are formed, whereas m the presence of these additives, only anti opening leading to trans isomers is observed [17, 18] (Table 2)... 

A typical feature of hydroformylation is the fact that both sides of the double bond are in principle reactive, so only ethene yields propanal as a single product. From propene, two isomers are formed linear or normal butanal and 2-methylpropanal (branched or iso product). With longer chain 1-alkenes, the isomerization of the double bond to the thermodynamically more favored internal positions is possible, yielding the respective branched aldehydes (Fig. 1). Frequently, terminal hydroformylation is targeted because of the better biodegradability of the products. Thus, not only stability, activity, and chemoselectivity of the catalysts are important. A key parameter is also the regioselectivity, expressed by the n/i ratio or the linearity n/(n+i). 

Competition studies reported by Kuwajima, " which also complement the results of Nakai," illustrate the limitations of the 3-effect as a tool for predicting the outcome of vinylsilane-terminated cyclizations (Scheme 4). Acylium ion initiated cyclizations of (7a) and (7b) gave the expected cyclopentenones (8a) and (8b). However, compound (7c), upon treatment with titanium tetrachloride, gave exclusively the cyclopentenone proiduct (8c) arising fr the chemoselective addition on the 1,1-disubstituted alkene followed by protodesilylation of the vinylsilane. The reversal observed in the mode of addition may be a reflection of the relative stabilities of the carbocation intermediates. The internal competition experiments of Kuwajima indicate that secondary 3-silyl cations are generated in preference to secondary carbocations (compare Schemes 3 and 4), while tertiary carbocations appear to be more stable than secondary 3-silyl cari ations, as judged by the formation of compound (te). 

Bulky diphosphites not only express a high selectivity toward 1-alkenes [255] but also for less reactive internal [256] and functionalized alkenes. Recently DSM and Du Pont reported on a ligand (24) which has a high regio- and chemoselectivity for the hydroformylation of methyl 3-pentenoate [253]. The synthesis of monophenols containing bulky substituents (25) is described in patents from Mitsubishi [257]. High yields with 1-alkenes and l/b ratios up to 20 are reported. 

Snider has found dialkyl aluminium halides to be excellent catalysts for this reaction and they can be used to stop the reaction after the first step. This is a real advance in the Prins reaction that otherwise tends to give a mixture of products by multiple addition of the aldehyde and intervention by various nucleophiles. A simple example is the addition of formaldehyde to the terpene limonene 208 catalysed by BF3. A single monoadduct 210 is formed in good yield.34 This must be a Lewis acid catalysed carbonyl ene reaction on the external double bond 209. Notice the excellent chemoselectivity in that the internal alkene is not attacked and the excellent regioselectivity in that hydrogen atoms at four other sites might have taken part in the reaction, but do not. 

The AD reaction was central in the preparation of (+)-cw-sylvaticin 41,27 a natural product found to have potent anti-tumor activity. The ability of this compound to inhibit ATP production by blockade of the mitochondrial complex I was thought to be the origin of this biological outcome. The AD reaction, in this example, exploited the preference of this reaction for the oxidation of 1,2-frans-alkenes over monosubstituted alkenes. The E,E-isomer of tetradecatetraene 42 could be chemoselectively dihydroxylated at both internal alkenes, while the terminal alkenes remained untouched. Thus, 43 was generated in excellent chemical yield. 

The silylformylation of 1-alkynes has been studied extensively affording (Z)-l-silyl-2-formyl-l-alkenes high regioselectivity. However, internal alkynes have not demonstrated high regioselectivity. Biffis et al. have reported using a cationic dirhodium(II) complex to achieve improved chemoselectivity for the silylformylation of internal alkynes.In addition, intramolecular silylformylation reactions were developed to aid in the regioselectivity of silylformylation of internal alkynes. ... 

The hydroboration of enamine is remarkable regio- and chemoselective as the boron adds to the electron-rich enamine double bond. Consequently, hydroboration of enamines and the treatment of the resulting trialkylboranes with methanol afford the corresponding alkenes in excellent yield [13]. The process is a general procedure for the synthesis of terminal alkenes from aldehydes and internal or cyclic alkenes from ketones (Eq. 24.5). 

The hydrosilylation of terminal alkynes disclosed by Trost can be applied to internal alkynes as well. i Remarkably, the (Z)-isomer is generated in this process, resulting from trans addition during hydrosilylation. The protodesilylation of these sily-lated products in the presence of copper(I) iodide and tetrabuty-lammonium fluoride (TBAF) or silver(I) fluoride (eq 15) leads to internal fraws-olefins. This two-step method is a useful synthetic transformation to access ( j-alkenes from internal alkynes. In contrast, the chemoselective reduction of alkynes to the corresponding ( -alkenes is conventionally accomplished readily with Lindlar s catalyst. The complementary process to afford ( )-olefins has proven much more difficult. Methods involving metal hydrides, dissolving metal reductions, low-valent chromium salts provide the desired chemical conversion, albeit with certain limitations. For example, functional substitution at the propargylic position (alcohols, amines, and carbonyl units) is often necessary to achieve selectivity in these transformations. Conversely, the hydrosilylation/protodesilyla-tion protocol is a mild method for the reduction of alkynes to ( )-alkenes. 

Alkenes undergo rapid hydroboration with 9-BBN as compared with internal alkynes and hence chemoselective hydroboration of enynes 18 can be achieved under these circumstances to obtain the borane 19 using 9-BBN as the hydroborating agent (Scheme 28.6). ... 

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