Substitution conjugate nucleophilic

The following transformation involves a conjugate nucleophilic addition reaction (Section 19.13) followed by an intramolecular nucleophilic acyl substitution reaction (Section 21.2). Show the mechanism. 

Cir—R S Nucleophilic substitution, conjugate addition and epoxide ring-opening h... 

Isolated instances of 1,4-addition reactions of other hetero-nucleophiles to 4-en-2-ynoic acids and derivatives have been reported172-174. Thus, treatment of methyl 4-methyl-4-penten-2-ynoate with phenolate provided the 3-phenoxy-substituted conjugated dienoate (equation 71)172, and the 1,4-addition of water-soluble phosphines to 4-octen-2-ynoic acid afforded dienylphosphonium salts which were transformed into the corresponding phosphine oxides (equation 72)174. 

SN1 SNlcA Nucleophilic substitution unimolecular. Nucleophilic substitution unimolecular, conjugate acid, when the leaving group departs only after protonation. Also called A1. 

The diene-Br2 complex is again in equilibrium with the reagents, and nucleophilic attack at carbon can be carried out either by the bromide of the ammonium bromide ion pair, formed at the moment of the electrophilic attack, or by the less nucleophilic pyridine added in excess in the reaction medium. It is noteworthy that this mechanism is characterized by a rate- and product-limiting nucleophilic step which should be quite insensitive to steric hindrance around the double bond. In agreement with a weak influence of the steric effects, pyridinium perbromide reacts in chloroform and tetrahydrofuran with substituted conjugated and non-conjugated dienes to give selectively (>95%) bromine addition to the more alkylated double bond (equation 44). 

These cycloadditions were originally considered by Woodward and Hoffmann to be allowed [ 2S + 2J cycloadditions5. More recent calculations suggest that these reactions arc quasi-per-icyclic [2 + 2 + 2] cycloadditions with very asynchronous bond formation6 8. syn Addition of the ketene to the alkene is always observed, as is required by a concerted cycloaddition. Furthermore, the carbonyl group of the ketene almost invariably adds exclusively to the least substituted, most nucleophilic end of the double bond. Similarly, the carbonyl group of the kctcnc adds to the more nucleophilic end of a conjugated diene. 

Pyrrolizin-3-one (386) undergoes conjugate nucleophilic addition of piperidine and thiophenol and electrophilic addition of hydrogen chloride to give a range of 1-substituted 1,2-dihydro-pyrrolizin-3-ones (387), (388), and (389) respectively the 1-chloro atom can readily be displaced by nucleophiles, including water (Scheme 129) <93CC1570>. 

As with other electrophilic substitutions, conjugate addition can be used in conjunction with nucleophilic capture of an indolenine intermediate. Marko and coworkers used such a reaction to synthesize a versatile intermediate in alkaloid synthesis [298]. The amide 106-A cyclized to 106-B, when exposed to Si02 in CH2CI2. The nucleophilic addition was then conducted in a separate step. The... 

Koo et al. have developed an efficient method for the preparation of diverse co-formyl-a,p-unsaturated carbonyl compounds 268 and 273 that relied on the Pb(OAc)4-promoted oxidative ring cleavage of cyclic 1,2-diols 267 and 272, respectively, which in turn can be readily obtained by the 1,2-addition of various nucleophiles to a cx -acetoxy-substituted conjugated cycloalkenones 266 and a-acetoxy cyclohexanone 271. The authors also optimized the conditions for the intramolecular MBH reactions of 268 and 273. The utility of this sequence is demonstrated by the syntheses of chromones 270 and the precursor (274) of the compound containing the 6,8-dioxabicyclo[3.2.1]octane ring (Scheme 1.98). ... 

Usually the functional moiety is covalently linked to the conjugated backbone, but it can be sometimes added to ECP as a dopant when it is under an ionic form e.g., sulfonated P-cyclodextrins have been successfiilly incorporated in one step as anionic dopants in PPy by electropolymerization [230]. In some cases, electrochemistry can be combined to chemical reactions to derive functional ECPs functional PANI materials can be obtained from the reduction of the emeraldine form by alkylthiols [255] and the functionality degree on the PANI backbone can be monitored by successive oxidation-reduction cycles various functionalized PANIs can also be synthesized through electrophilic substitution or nucleophilic addition reactions [256]. For example. Figure 18.10 shows the similar electrochemical behaviors of sulfonated PANI made from reduction of emeraldine by sulfite salt followed by reoxidation, compared to thin films deposited from solution of highly sulfonated PANIs. 

The additives of water can serve as mechanistic probes and aid in obtaining true mechanistic understanding in some organocatalytic reactions [123]. The water is nucleophile in palladium-catalyzed oxidative carbo-hydroxylation of allene-substituted conjugated dienes [124]. This is an example of Pd- catalyzed oxidation leading to C -C bond formation in water with subsequent water attack on a (rr-allyl) palladium intermediate. The different effect of the water concentration on the intra- and extra-diol oxygenations of 3,5-di-tert-butylcatechol with O2, catalyzed by FeC in tetrahydrofuran-water indicates that the intermediates for two reactions are different (model for Catechol-2,3-dioxygenases) [125]. 

Notably, cyclic enone could also be employed to form the Michael adducts with high enantioselectivity and diastereo-selectivity as well as excellent yields. These results represent the first examples of a highly enantioselective and diastereo-selective organocatalytic conjugate addition of a tri-substituted carbon nucleophile to a cyclic enone. 

Phosphonyl and phosphinyl nitroso alkenes (607) reacted with cychc conjugated nucleophilic dienes such as cyclopentadiene or cyclohexadiene (608) and silyl-substituted cyclopentadiene (609) to afford [4+2]-hetero Diels-Alder-type 1,2-oxazines cycloadducts (610) and (612) The nitroso alkenes participated as dienophile components and the cyclic olefins acted as the 471-electron (diene) systems. Cycloadducts (611), derived from cyclopentadiene, underwent a new aza-Cope type [3,3]-sigmatropic rearrangement to give 1,2-oxazines (612) (Scheme 150). ... 

The formation of the above anions ("enolate type) depend on equilibria between the carbon compounds, the base, and the solvent. To ensure a substantial concentration of the anionic synthons in solution the pA" of both the conjugated acid of the base and of the solvent must be higher than the pAT -value of the carbon compound. Alkali hydroxides in water (p/T, 16), alkoxides in the corresponding alcohols (pAT, 20), sodium amide in liquid ammonia (pATj 35), dimsyl sodium in dimethyl sulfoxide (pAT, = 35), sodium hydride, lithium amides, or lithium alkyls in ether or hydrocarbon solvents (pAT, > 40) are common combinations used in synthesis. Sometimes the bases (e.g. methoxides, amides, lithium alkyls) react as nucleophiles, in other words they do not abstract a proton, but their anion undergoes addition and substitution reactions with the carbon compound. If such is the case, sterically hindered bases are employed. A few examples are given below (H.O. House, 1972 I. Kuwajima, 1976). 

Epoxide opening with nucleophiles occurs at the less substituted carbon atom of the oxlrane ting. Cataiytic hydrogenolysis yields the more substituted alcohol. The scheme below contains also an example for trons-dibromination of a C—C double bond followed by dehy-drobromination with strong base for overall conversion into a conjugated diene. The bicycKc tetraene then isomerizes spontaneously to the aromatic l,6-oxido[l0]annulene (E. Vogel, 1964). 

When butadiene is treated with PdCU the l-chloromethyl-7r-allylpalladium complex 336 (X = Cl) is formed by the chloropalladation. In the presence of nucleophiles, the substituted 7r-methallylpalladium complex 336 (X = nucleophile) is formed(296-299]. In this way, the nucleophile can be introduced at the terminal carbon of conjugated diene systems. For example, a methoxy group is introduced at the terminal carbon of 3,7-dimethyl-I,3,6-octatriene to give 337 as expected, whereas myrcene (338) is converted into the tr-allyl complex 339 after the cyclization[288]. 

Solvolysis reaction (Section 8 7) Nucleophilic substitution m a medium m which the only nucleophiles present are the solvent and its conjugate base... 

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