Alkenyl substituents

Section 11 16 Addition reactions to alkenylbenzenes occur at the double bond of the alkenyl substituent and the regioselectivity of electrophilic addition is governed by carbocation formation at the benzylic carbon See Table 11 2... 

Alkyl groups are as we saw when we discussed the nitration of toluene in Sec tion 12 10 activating and ortho para directing substituents Aryl and alkenyl substituents resemble alkyl groups in this respect they too are activating and ortho para directing... 

As with alkyl and alkenyl substituents derived from alkanes and alkenes, respectively, alkynyl groups are also possible. 

Cyclizations of A-acyliminium ions containing a 3-alkenyl substituent tethered to nitrogen usually proceed with preferential formation of a six-mentbered ring via a chair-like transition state, if the alkene does not have an electronic bias. 

Epoxides with alkenyl substituents undergo alkylation at the double bond with a double-bond shift accompanying ring opening, leading to formation of allylic alcohols. 

Some typical proton and carbon chemical shift and coupling constant data for allylic and benzylic systems are given in Scheme 3.54. An alkenyl substituent or a phenyl substituent on either a CH2F or a —CHF- group has virtually no effect upon that carbon s chemical shift, and they also only affect the proton chemical shift by about 0.5 ppm. 

The P-lactam antibiotic cephalosporin is one of the most important drugs for the treatment of bacterial infections. Recently, several new compounds such as ce-fadroxil (2-161), cephalexin (2-162), cefixime (2-163), and cefzil (2-167) have been isolated, which contain an alkyl or alkenyl substituent instead of an acetoxymethyl group at C-3 (Scheme 2.37 and 2.38) [88]. 

Cyclization of oximes containing y-,d-, or oo-alkenyl substituents, upon treatment with /V-bromosuccinimide (NBS) or iodine leads in good yields to the corresponding cyclic nitrones or their dimeric H- bonded hydriodide salts (290). 

It is observed that insertion into a zirconacyclopentene 163, which is not a-substituted on either the alkyl and alkenyl side of the zirconium, shows only a 2.2 1 selectivity in favor of the alkyl side. Further steric hindrance of approach to the alkyl side by the use of a terminally substituted trans-alkene in the co-cyclization to form 164 leads to complete selectivity in favor of insertion into the alkenyl side. However, insertion into the zirconacycle 165 derived from a cyclic alkene surprisingly gives complete selectivity in favor of insertion into the alkyl side. In the proposed mechanism of insertion, attack of a carbenoid on the zirconium atom to form an ate complex must occur in the same plane as the C—Zr—C atoms (lateral attack 171 Fig. 3.3) [87,88]. It is not surprising that an a-alkenyl substituent, which lies precisely in that plane, has such a pronounced effect. The difference between 164 and 165 may also have a steric basis (Fig. 3.3). The alkyl substituent in 164 lies in the lateral attack plane (as illustrated by 172), whereas in 165 it lies well out of the plane (as illustrated by 173). However, the difference between 165 and 163 cannot be attributed to steric factors 165 is more hindered on the alkyl side. A similar pattern is observed for insertion into zirconacyclopentanes 167 and 168, where insertion into the more hindered side is observed for the former. In the zirconacycles 169 and 170, where the extra substituent is (3 to the zirconium, insertion is remarkably selective in favor of the somewhat more hindered side. 

More recently Miron and Lee (1962) analysed the hydrocarbons removed from strong acid catalysts in some detail, and suggested unsaturated cyclic structures. These structures contain from one to five five-membered rings with various methyl and alkenyl substituents and a minimum of two double bonds per molecule. However, during their drowning procedures, as the acid is diluted, considerable polymerization occurs. This conclusion is based on work by Hodge (1963), who showed that cyclopentenyl cations are rapidly destroyed by alkylation at 10 m concentrations in 35% H2SO4. 

Undoubtedly, further work will be necessary in order to get a solid background for silyl radical cyclizations. In particular, further investigations on the nature of the pendant alkenyl substituent as well as on the ring size and substituent effects on the silicon in the ring expansion can be expected in the future. 

In the case of 489, the product 490 cyclizes to the isoquinolone 491, and the amide substituent is a required part of the target molecule" . However, it frequently occurs that the amide substituent is not required in the final product, and the acid-sensitive alkenyl substituent of 492 has been used as a solution to the problem of cleaving a C—N bond in the product (Scheme 193) ° °. Weinreb-type amides 493 can also be laterally lithiated, and the methoxy group removed from 494 by TiCU" . Hydrazones similarly can be laterally lithiated and oxidatively deprotected. ... 

The oxidation of substituted pyridines to iV-oxides was reported by Sharpless and coworkers to proceed with yields between 78 and 99% (Scheme 154). A variety of substituents like electron donor as well as acceptor groups and alkenyl substituents are tolerated. In 1998, Sharpless and coworkers reported an alternative method for the preparation of pyridine-A-oxides in which the MTO/H2O2 catalyst could be replaced by cheaper inorganic rhenium derivatives (ReOs, Re207, HOReOs) in the presence of bis(trimethylsilyl) peroxide (equation 73). Yields of the prepared A-oxides after simple workup (filtration and bulb to bulb distillation) ranged from 70-98%. Molecular sieves slowed down the reaction while small amounts of water (0-15%) were essential for the reaction. Both electron-poor or electron-rich pyridines give high yields of their A-oxides and while para-... 

Unfortunately, this process gave good results only with bulky substituents at the acetylenic terminus in 104 and, surprisingly, Jeffery s conditions—but without a quaternary ammonium salt—were found to work best. With an additional alkenyl substituent at the acetylenic terminus as in the cyclohexenyl-substituted 2-bromonona-l,8-dien-6-yne 109, the co-cyclization with bicyclopropylidene 12, under these conditions, leads to 110. This transformation involves two consecutive 67r-electrocyclizations of the initially formed cross-conjugated pentaene 111, which was not isolated (Scheme 30). ... 

Cyclization of some jS-dicarbonyl compounds. In the presence of this reagent and a catalyst (12, />-TsOH, Znl2), /J-dicarbonyl compounds containing an alkenyl substituent undergo cyclization with incorporation of a phenylseleno group. 

Figure 5.15. Preparation of cyclic peptides by ring-closing metathesis in solution, and lengths of the N-alkenyl substituent required for ring formation [123],...

The cyclisation of alkenes by low valent titanium has also been applied to intramolecular processes. Thus the reduction of titanocenes bearing pendant alkenyl substituents [TiCl2(r -C5Me4XCH = CHR)2] (X = SiMe2, CH2, CHMe R = H, Me) provides chiral titanacyclopentanes shown in Scheme 2.16 The titan-acyclopentanes could then be cleaved with HC1 to provide new titanocene dichlorides in which the two cyclopentadienyl ligands were linked by a hydrocarbon chain. 

Nitriles are well known to undergo acid and alkaline hydrolysis (Figure 13.5), but there is only one recent report of neutral hydrolysis. Thus, methacrylonitrile, even though it is conjugated with an alkenyl substituent, should undergo both acid-catalyzed and base-mediated hydrolysis via a pathway similar to that for alkyl and aryl nitriles. The amide is a likely intermediate product for nitrile hydrolysis, but it is reactive as well and can undergo acid- and base-mediated hydrolysis to the carboxylic acid and ammonia. The... 

Diallylphosphonate, shown in Figure 18.3, has two alkenyl substituent groups. Information is lacking on its toxicity, although compounds with allyl groups tend to be relatively toxic. Incidents have been reported in which this compound has exploded during distillation. 

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