Alkene derivatives intramolecular reactions

In the presence of a double bond at a suitable position, the CO insertion is followed by alkene insertion. In the intramolecular reaction of 552, different products, 553 and 554, are obtained by the use of diflerent catalytic spe-cies[408,409]. Pd(dba)2 in the absence of Ph,P affords 554. PdCl2(Ph3P)3 affords the spiro p-keto ester 553. The carbonylation of o-methallylbenzyl chloride (555) produced the benzoannulated enol lactone 556 by CO, alkene. and CO insertions. In addition, the cyclobutanone derivative 558 was obtained as a byproduct via the cycloaddition of the ketene intermediate 557[4I0]. Another type of intramolecular enone formation is used for the formation of the heterocyclic compounds 559[4l I]. The carbonylation of the I-iodo-1,4-diene 560 produces the cyclopentenone 561 by CO. alkene. and CO insertions[409,4l2]. 

Some novel bicyclic pyrylium salts arise when a dicarboxylic acid derivative is used. For example, although decanedioyl chloride did not diacylate isobutene, possibly because of strain inherent in the expected product, 1,12-dodecanedioyl chloride gave a very low yield of the pyrylium salt (658) (62T1079). A dilute solution of the reactants in nitromethane was used in order to favour the intramolecular reaction. In a similar vein, a macrocyclic alkene, such as cyclododecene, undergoes diacylation to the bicyclic salt (659) (68TL4643), whilst... 

The inclusion of a separate chapter on catalysed cyclopropanation in this latest volume of the series is indicative of the very high level of activity in the area of metal catalysed reactions of diazo compounds. Excellent, reproducible catalytic systems, based mainly on rhodium, copper or palladium, are now readily available for cyclopropanation of a wide variety of alkenes. Both intermolecular and intramolecular reactions have been explored extensively in the synthesis of novel cyclopropanes including natural products. Major advances have been made in both regiocontrol and stereocontrol, the latter leading to the growing use of chiral catalysts for producing enantiopure cyclopropane derivatives. 

Carboxylic acid chlorides and chloroformate esters add to tetrakis(triphenylphosphine)palladium(0) to form acylpalladium derivatives (equation 42).102 On heating, the acylpalladium complexes can lose carbon monoxide (reversibly). Attempts to employ acid halides in vinylic acylations, therefore, often result in obtaining decarbonylated products (see below). However, there are some exceptions. Acylation may occur when the alkenes are highly reactive and/or in cases where the acylpalladium complexes are resistant to decarbonylation and in situations where intramolecular reactions can form five-membered rings. 

Doubly acceptor-activated imines with an intramolecular alkene moiety such as 29 can cyclize according to an electrophilic mechanism to give pyrrolidine, piperidine or azepine derivatives. This reaction is induced by stoichiometric amounts of Lewis acids, preferably trialkylsilyl triflates [38]. In certain cases FeCl3 can also be used, for example for the preparation of azepinolactone 30 from imine 29 (Scheme 8.10) [39]. Catalytic amounts of FeCl3 are required for the addition of diethyl phosphite to an... 

The intramolecular version presents a very useful synthetic route to various polycyclic compounds. Even terminal alkenes give cyclopentenones in good yields, assisted by the addition of /V-methylmorpholine N-oxide (NMO) [85], The addition of trimethylamine A -oxidc also dramatically accelerates the reaction in the presence of oxygen, and both inter- and intramolecular reactions proceed at 0°C to room temperature [86]. The reaction was found to proceed rapidly at 25 °C by the addition of aqueous NH4OH [87]. Numerous applications to natural product syntheses have been reported. The tri- and tetracyclic skeletons 214 for crinipellin B, from 213 [88], and the triquinacene derivative 216, from 215, have been constructed [89,90], These results show that internal alkynes and terminal alkenes react smoothly in the intramolecular reactions. Domino reaction of the endiyne 217 produced the strained molecule of oxa[5.5.5.5]fenestrenedione (219) via 218 [91]. 

A similar cyclisation of an alkene derived from geranyl acetate 24 by dihydroxylation and formation of the epoxide 26 leads to a substituted cyclohexane 28. The Lewis acid ZrCU is used to open the epoxide and the alkene attacks intramolecularly 27 to give eventually the ryn-compound 28 with both substituents equatorial. The alignment of the alkene and the epoxide in a chair conformation 27a is responsible for the diastereoselectivity Note the regioselectivity the less substituted end of the alkene attacks the more substituted end of the epoxide 27. These are just two examples of the very many ordinary ionic reactions that can be used to make six-membered rings. 

Due to their reduced aromatic character, naphthalene derivatives also frequently undergo ortho cycloaddition with alkenes (Sch. 4). 1-Cyano-naphthalene 13 reacts with cyclohexadiene to yield the regioisomeric ortho adducts 14 and 15 in good yields [34]. Two regioisomers 17 and 18 were also obtained from the intramolecular reaction of the 1-cyanonaphthalene derivative 16 [35]. The proportion of the two isomers depends on the solvent polarity. 

Sufficient information about the reaction has been gathered to allow fairly accurate predictions of yield as well as of stereo- and regioselectivity.176177 The reaction proceeds via the formation of hexacarbonylalkyne-dicobalt complexes and is remarkably tolerant of functional groups in both the alkyne and the alkene. The intramolecular Pauson-Khand reaction is an effective way of preparing bi- and polycyclic systems, and the cyclization of 1,6-heptenyne derivatives to give bicyclo[3.3.0]oct-l-en-3-ones has been the most popular application of the Pauson-Khand reaction in natural product synthesis [Eq. (17)]. 

Cycloaddition of 7-oxanorbomadiene derivatives has been reported (Scheme 247). 5-Bromo-7-azanorbomenes undergo regioselective Pauson-Khand reaction to give (168). The bromine is lost during the reaction (Scheme 248). A-Protected alkynylamides undergo intramolecular reactions with alkenes to give 2-amidocyclopentenones (Scheme 249). 

Chiral Auxiliary for Asymmetric Induction. Numerous derivatives of (—)-8-phenylmenthol have been utilized for asymmetric induction studies. These include inter- and intramolecular Diels-Alder reactions, dihydroxylations, and intramolecular ene reactions of a,p-unsaturated 8-phenylmenthol esters. These reactions usually proceed in moderate to good yield with high diastereofacial selectivity. a-Keto esters of 8-phenylmenthol (see 8-Phenylmenthyl Pyruvate) have been used for asymmetric addition to the keto group, as well as for asymmetric [2 -F 2] photoadditions and nucleophilic alkylation. Ene reactions of a-imino esters of 8-phenylmenthol with alkenes provide a direct route to a-amino acids of high optical purity. Vinyl and butadienyl ethers of 8-phenylmenthol have been prepared and the diastereofacial selectivity of nitrone and Diels-Alder cycloadditions, respectively, have been evaluated. a-Anions of 8-phenylmenthol esters also show significant diastereofacial selectivity in aldol condensations and enantiose-lective alkene formation by reaction of achiral ketones with 8-phenylmenthyl phosphonoacetate gives de up to 90%. ... 

Monoaryldiazomethanes, readily prepared by a number of methods, are the carbene precursors most frequently used for the synthesis of arylcyclopropanes. When such diazo compounds are decomposed photochemically, thermally, or by using various transition-metal salts in the presence of an alkene, arylcyclopropanes are formed. The yield is often quite high, but in a number of cases cyclopropane formation has been hampered by competing reactions, of which, disregarding intramolecular reactions, azine formation, stilbene formation, and hydrogen abstraction followed by dimerization are the most predominant. Many aspects related to the use of diazomethane derivatives as carbene precursors have been thoroughly discussed by Wentrup. ... 

Other interesting fused thiophene derivatives include the photorearrangement of thio-phenetriptocene to form semibullvalene (96) <93CL68i>. Photochemically induced intramolecular reaction of thiophenones with alkenes in methanol produces novel tricyclic thiolane derivatives such as (97) <88HCA502>. 

Apart from such intramolecular reactions, exclusively electronically activated alkene derivatives such as TCNE [53], maleic anhydride, E- and Z-ethylenedi-... 

The intramolecular reaction of alkenes with various O and N functional groups offers useful synthetic methods for heterocycles [15,16,40]. Reaction of unsaturated carboxylic acids affords lactones by either exo or endo cyclization depending on the positions of the double bond. Both 5-hexenoic acid (83) and 4-hexenoic acid (84) were converted to five- or six-membered lactones depending on the solvents and bases [41,42]. Oxidative cyclization of the optically active 4-pentenoic acid derivative 85 (85 % ee) using O2 as an oxidant afforded the y-lactone 86 with 86 % ee in 84 % yield [43]. 2-Vinylbenzoic acid (87) was converted to isocoumarin (88), but not to the five-membered lactone [41,44]. 

In contrast to facile reactions of aryl halides with alkenes and alkynes, reactions of aromatic compounds with aryl halides have received less attention. Only intramolecular arylation of benzene derivatives, except phenols, is known [1]. On the other hand, electron-rich heterocycles such as ffirans, thiophenes, pyrroles, oxa-zoles, imidazoles, and thiazoles undergo facile inter- and intramolecular arylation with aryl halides. These are called heteroaryl Heck reactions [2]. 

Ni(COD)2/PiPr3 catalyses intramolecular addition of pyridone derivatives across tethered alkenes in the presence of AlMCs. The reaction proceeds mainly in an exo-trig fashion to form bicyclic products in good yields. The intermolecular reaction only occurs when a vinylarene is employed and results in branched all lated pyridones. However, a modified catalyst system can promote intermolecular reaction between pyridone derivatives and aliphatic alkenes. Moreover, the reaction selectively gives linear allq lated pyridones (Scheme 14.74). The reaction occurs at the C6 position of pyridones exclusively. If the C6 position is occupied by a substituted group, the alleviation can occur at the C4 position. For example, l,6-dimethyl-2-pyridone undergoes alkylation at the C4 position when the reaction was run at 100... 

The reductive coupling of bis(enones) is another reaction class that may involve alkene-derived metallacyclopentanes. Treatment of a symmetrical bis(enone) 89 tvith bis(r] -cy-cloocta-l,5-diene)nickel(0) (2) and butyllithium/zinc(II) chloride leads to coupling of the two enone -carbons followed by an intramolecular aldol addition to afford bicyclo[3.3.0]-octanols 90 (Scheme Sterically hindered enones have also been shovm to partic-... 

Intramolecular oxidative aminations of olefins have alsobeen studied, and many of these intramolecular processes were observed prior to the analogous intermolecular variants. The oxidative aminations of alkenes with arylamines and arylamine derivatives catalyzed by palladium complexes were shown by Hegedus to form indoles (Equation 16.120). These reactions were conducted with orf/io-allylaniline and ort/zo-allylaniline derivatives as substrate, Pd(NCMe)jCl2 as catalyst, and benzoquinone as oxidant. Intramolecular reactions of N-tosylated aliphatic amines were reported by Larock. ° For example, the tosylamide in Equation 16.121 imdergoes cyclization in high yield in the presence of dioxygen with Pd(OAc)j as catalyst in DMSO. A related reaction (Equation 16.122) was reported recently in toluene solvent with added pyridine. ... 

The complexity of this reaction scheme already points out the necessary time-balance between oxidative addition, CO insertion versus deinsertion (decarbonylation), acylpalladation, carbopaUadation, and dehydropalladation events to have a selective acylpallada-tion-type reaction. This has been more recently addressed by selecting acyl chlorides that could not readily undergo dehydropalladation, hence stabilizing the organopalladium intermediates to favor their intramolecular reaction with alkenes. For instance, Pd(OAc)2 catalyzes the reaction of benzoyl chloride derivatives with enol ethers (R = OEt, Scheme 3) to give the corresponding acylpalladation products typically in 40-77% yields. " ... 

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