Dienes from nucleophilic addition

The complementary approach, activation of unsaturated hydrocarbons toward electrophilic attack by complexation with electron-rich metal fragments, has seen limited investigation. Although there are certainly opportunities in this area which have not been exploited, the electrophilic reactions present a more complex problem relative to nucleophilic addition. For example, consider the nucleophilic versus electrophilic addition to a terminal carbon of a saturated 18-electron metal-diene complex. Nucleophilic addition generates a stable 18-electron saturated ir-allyl complex. In contrast, electrophilic addition at carbon results in removal of two valence electrons from the metal and formation of an unstable ir-allyl unsaturated 16-electron complex (Scheme 1). 

Nucleophilic attack on neutral complexes of ii -diene ligands is less common than attack on cationic complexes of these ligands but is known. In one case, Semmelhack reported the reactions of iron complexes of acyclic ii -dienes with reactive carbanions such as LiC-MCjCN and LiCHPhj (Equation 11.47). At -78 °C, the reaction is rapid, and kinetically controlled. Attack occurs at an unsubstituted, internal position to give an unstable o-alkyl Ti -olefin complex. This addition is reversible below 0 °C, and the more stable product is then generated from nucleophilic addition at a terminal position of the diene to give the thermodynamically more stable T -allyl complex. Cyclohexadiene complexes are similarly alkylated by a range of carbanions. ... 

Examination of the reactivity of acyclic (diene)Fe(CO)3 complexes indicates that this nucleophilic addition is reversible. The reaction of (C4H6)Fe(CO)3 with strong carbon nucleophiles, followed by protonation, gives olefinic products 195 and 196 (Scheme 49)187. The ratio of 195 and 196 depends upon the reaction temperature and time. Thus, for short reaction time and low temperature (0.5 h, —78 °C) the product from attack at C2 (i.e. 195) predominates while at higher temperature and longer reaction time (2 h, 0 °C) the product from attack at Cl (i.e. 196) predominates. This selectivity is rationalized by kinetically controlled attack at the more electron-poor carbon (C2) at low temperature. Nucleophilic attack is reversible and, under conditions where an equilibrium is established, the thermodynamically more stable (allyl)Fe(CO)3" is favored. The regioselectivity for nucleophilic attack on substituted (diene)Fe(CO)3 complexes has been reported187. The... 

Finally, reaction of 2,4-diphenyl-5(4//)-oxazolone 322 with 4-phenyl-A -tosyl-1-azabuta-1,3-diene was found to be highly dependent on the experimental conditions. At room temperature the sole product was 323 that arises from alkylation of 322 by addition at the imine carbon. However, heating 322 and 4-phenyl-A-tosyl-1-azabuta-1,3-diene gave rise to several products including a 2-pyridone 324, 2,3,6-triphenylpyridine 325, and the pentasubstituted pyrroles 326 and 327. The authors postulated two different reaction mechanisms. Here, both a 1,3-dipolar cycloaddition of the oxazolone and a nucleophilic addition of the oxazolone are possible and that may account for the formation of 324—327. The marked differences in reactivity of 4-phenyl-A-tosyl-l-azabuta-l,3-diene relative to A-alkyl- or A-aryl-1-aza-1,3-dienes was attributed to the powerful electron-withdrawing nature of the tosyl group (Scheme 7.107). ... 

The thiylation of conjugated dienes and allenes proceeds as expected. Thus, the acid-catalyzed reaction of thiols with 1,3-dienes affords the 1,4-addition product,552 whereas the nucleophilic addition to allene provides the product arising from sulfur attack at the central carbon (equations 303 and 304).553... 

A general method of synthesis of l-hetera-4-telluracyclohexa-2,5-dienes 90 is founded in the nucleophilic addition of telluride anion to type 91 diacetylene derivatives. The telluride dianion is prepared in situ from the elements in liquid ammonia. The reaction was carried out with methanol or mixtures with DMSO and liquid ammonia as solvents, with the following diacetylenes di(l-alkynyl)sulfides (73RTC1326), I-alkynylethynyl sulfides (75RTCI63), di(l-alkynyl)sulfones (78RTC244), and di(l-alkynyl)phosphi-noxides (75RTC92). 

Several catalytic systems have been investigated for hydroamination of unsaturated bonds [16]. Takahashi et al. reported the telomerization of 1,3-dienes in the presence of an amine leading to octadienylamine or allylic amines when palladium catalysts are used in association with monodentate or bidentate phosphine ligands, respectively [17]. Dieck et al. demonstrated the beneficial effect of addition of an amine hydroiodic salt in the hydroamination reaction of 1,3-dienes in which the allylic amines are produced via an intermediate Jt-allyl palladium complex [18]. Coulson reported the Pd-catalyzed addition of amines to allenes where dimerization is incorporated [4]. This reaction presumably proceeds via a cyclic palladium intermediate in which the Pd activates the olefinic bond for nucleophilic attack the reactions are therefore different from pronucleophilic additions. 

Electrophilic additions to conjugated dienes usually involve allylic cations as intermediates. Unlike simple carbocations, an allylic cation can react with a nucleophile at either of its positive centers. Let s consider the addition of HBr to buta-1,3-diene, an electrophilic addition that produces a mixture of two constitutional isomers. One product, 3-bromobut-l-ene, results from Markovnikov addition across one of the double bonds. In the other product, 1 -bromobut-2-ene, the double bond shifts to the C2—C3 position. 

Hydride abstraction from dienyl tricarbonyl iron complexes furnishes cationic dienyl tricarbonyl iron complexes. For example, reaction of the diene-iron tricarbonyl complex (115) with triphenyhnethyl hexafluorophosphate followed by trimethylsilyl cyanide furnished with excellent regio- and stereoselectivity a new diene iron tricarbonyl complex (116) (Scheme 170). Excellent regio- and stereoselectivity is seen upon reaction of the cationic complex (116) with trimethylsilyl cyanide (TMS-CN) (Scheme 170). Reduction of the nitrile affords a spirocyclic lactam complex. Intramolecular cyclization of in situ formed enols furnishes spirocyclic compounds again with excellent stereoconfrol (Scheme 171). An interesting example of hydride transfer from a cyclohexadiene ring to a pendant aldehyde followed by nucleophilic addition is seen in Scheme 172. 

The addition of oxygen and chloride nucleophiles to dienes transiently activated by catalytic Pd is a practical process for production of 1,4-disubstituted 2-alkenes from 1,3-dienes however, it is not useful with carbon nucleophiles. Examples of carbon nucleophile addition to Fe° and Mo complexes show useful selectivity, but only in stoichiometric processes, and few applications have appeared. 

There is an alternative mechanism for halide replacement, following the sequence of nucleophile addition, protonation, and elimination of HX. In this pathway, the addition of the nucleophile need not be at the ipso position it can be ortho to halide leading to cine substitution or it can be at the meta or para positions, leading to tele substitution. The processes depend on the formation of the cyclohexadienyl anion intermediates in a favorable equilibrium (carbon nucleophiles from carbon acids with P a > 22 or so), protonation (which can occur at low temperature with even weak acids such as acetic acid), and hydrogen shifts in the proposed diene-chromium intermediates. Hydrogen shifts lead to an isomer that allows elimination of HX and regeneration of an arene chromium complex, now with the carbanion unit indirectly substituted for X (Scheme 40). ... 

Kobayashi et al. found that lanthanide triflates were excellent catalysts for activation of C-N double bonds —activation by other Lewis acids required more than stoichiometric amounts of the acids. Examples were aza Diels-Alder reactions, the Man-nich-type reaction of A-(a-aminoalkyl)benzotriazoles with silyl enol ethers, the 1,3-dipolar cycloaddition of nitrones to alkenes, the 1,2-cycloaddition of diazoesters to imines, and the nucleophilic addition reactions to imines [24], These reactions are efficiently catalyzed by Yb(OTf)3. The arylimines reacted with Danishefsky s diene to give the dihydropyridones (Eq. 14) [25,26], The arylimines acted as the azadienes when reacted with cyclopentadiene, vinyl ethers or vinyl thioethers, providing the tet-rahydroquinolines (Eq. 15). Silyl enol ethers derived from esters, ketones, and thio-esters reacted with N-(a-aminoalkyl)benzotriazoles to give the /5-amino carbonyl compounds (Eq. 16) [27]. The diastereoselectivity was independent of the geometry of the silyl enol ethers, and favored the anti products. Nitrones, prepared in situ from aldehydes and N-substituted hydroxylamines, added to alkenes to afford isoxazoli-dines (Eq. 17) [28]. Addition of diazoesters to imines afforded CK-aziridines as the major products (Eq. 18) [29]. In all the reactions the imines could be generated in situ and the three-component coupling reactions proceeded smoothly in one pot. 

Cyclopropenes, even unactivated ones, exhibit extraordinarily high reactivity in both electrophilic and nucleophilic addition reactions. They are also good dienophiles and react with a variety of conjugated dienes including acyclic 1,3-dienes, alicyclic 1,3-dienes, anthracenes and furans. An endo selectivity is usually observed. An alkyl or aryl substituent at the 3-position of cyclopropene sterically hinders the Diels-Alder addition and thus 3,3-dialkyl- and 3,3-diarylcyclopropenes exhibit a reduced dienophilicity (equation 131) . On the other hand, numerous Diels-Alder reactions have been reported for 3,3-dicyano- and 3,3-dihalocyclopropenes. The reactions of 3-monosubsti-tuted cyclopropenes with the diene take place stereoselectively from the less crowded side of the substrates (equation 132) °. 

The addition of a noii-stabilized carbon nucleophile and another nucleophile to a conjugated diene has similarities to the addition of H-Nu (cf. Section 8.2.1). The formation of RPdX from oxidative addition of RX and Pd(0) corresponds to the genei-ation of a palladium hydride species in the H-Nu addition (Scheme 8-3). 

When 2 was treated with only one equivalent of acetone, no product derived from the reaction of 2 with two molecules of acetone was observed, indicating that in the presence of 2, the initially formed adduct 12 did not add competitively to the unreacted acetone. This feature allowed both acetone and, subsequently, added carbon dioxide to be delivered to the original diene at the desired positions. However, if excess acetone was used, 12 underwent further nucleophilic addition to the ketone, yielding the corresponding diol. Therefore, it was essential to not use more than 1 Eq of acetone for the synthesis of 16. 

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