Alcohols heteroatomic nucleophiles

Regio- and diastereoselective rhodium-catalyzed tandem allylic alkylation of 71 with stabilized carbon and heteroatom nucleophiles 72 followed by the PK annulation by the same catalyst was described by Evans and co-workers. Alkylation of an optically active allylic alcohol carbonate 71 proceeds in a regio- and stereospecific manner successfully at 30 °C by 7r-acidic Rh(i) catalysts (Equation (41)). The resultant product then undergoes the PKR with the aid of the pre-existing catalyst under GO pressure at elevated temperature. ... 

Because of their high reactivity, these complex salts react rapidly and regiospecifically, at low temperature, with a number of carbon and heteroatomic nucleophiles, including thiols, amines, and alcohols. Finally, exposure of the double bond takes place under particularly mild conditions so that isomerization of the (3,Y-unsaturated carbonyl system may be avoided. The present scope of reactions with these vinyl cation synthons is summarized in [able I. 

The 1,2-diX relationship presents a different series of opportunities in which we use the second functionality to make the right carbon atom electrophilic. The amino, thio- and alkoxy- alcohols 33 to 35 all fit the pattern 36 and can be disconnected to the usual heteroatom nucleophile and the synthon 37. 

For compounds with a 1,2-relationship 5 we used an epoxide 6 at the alcohol oxidation level in combination with a heteroatom nucleophile. Disconnecting the corresponding C-C bond 7, we use the same epoxide and a carbon nucleophile such as RLi or RMgBr. 

Only three heteroatom nucleophiles add to a significant extent to carbonyl compounds without being followed by secondary reactions such as SN1 reactions (Section 9.2) or El reactions (Section 9.3) H20, alcohols, and, should the substitution pattern be suitable, the carbonyl compound itself. 

Investigation of the reaction of 3,3-disubstituted 1,2-dioxetanes with various heteroatom nucleophiles establishes the SN2 reactivity of these strained peroxides [134]. As reported in Sch. 80 for dioxetane 141, the sterically exposed oxygen of the peroxide bond becomes the site of nucleophilic attack to produce an anionic or zwitterionic adduct 142. Different reaction channels become available for the intermediate which depend on the chemical nature of the nucleophile. So epoxy alcohol 143, p-hydroxy hydroxylamine 144, diol 145, cyclic carbonate 146, and cyclic sulfite 147 can be obtained (Sch. 80) [134],... 

Nucleophilic attack on ( -alkene)Fp+ cations may be effected by heteroatom nucleophiles including amines, azide ion, cyanate ion (through N), alcohols, and thiols (Scheme 39). Carbon-based nucleophiles, such as the anions of active methylene compounds (malonic esters, /3-keto esters, cyanoac-etate), enamines, cyanide, cuprates, Grignard reagents, and ( l -allyl)Fe(Cp)(CO)2 complexes react similarly. In addition, several hydride sources, most notably NaBHsCN, deliver hydride ion to Fp(jj -alkene)+ complexes. Subjecting complexes of type (79) to Nal or NaBr in acetone, however, does not give nncleophilic attack, but instead results rehably in the displacement of the alkene from the iron residue. Cyclohexanone enolates or silyl enol ethers also may be added, and the iron alkyl complexes thus produced can give Robinson annulation-type products (Scheme 40). Vinyl ether-cationic Fp complexes as the electrophiles are nseful as vinyl cation equivalents. ... 

The reactivity of acychc (pentadienyl)iron cations with carbon and heteroatom nucleophiles has been examined. Nucleophilic attack may occur on either the cisoid or transoid conformation of the ligand. In general, it has been found that attack by weak nucleophiles (water, alcohols, weakly basic... 

Several heteroatom nucleophiles, for example, amines, alcohols, thiols, carboxylates, and dialkylphosphines, undergo Michael addition reactions with alkene- and alkyne-substituted carbene complexes. Reaction of alkyne-substituted chromium carbenes with urea affords products derived from Michael... 

Intermolecular Nucleophilic Substitution with Heteroatom Nucleophiles. A patent issued in 1965 claims substitution for fluoride on fluorobenzene-Cr(CO)3 in dimethyl sulfoxide (DMSO) by a long list of nucleophiles including alkoxides (from simple alcohols, cholesterol, ethylene glycol, pinacol, and dihydroxyacetone), carboxylates, amines, and carbanions (from triphenyhnethane, indene, cyclohexanone, acetone, cyclopentadiene, phenylacetylene, acetic acid, and propiolic acid). In the reaction of methoxide with halobenzene-Cr(CO)3, the fluorobenzene complex is ca. 2000 times more reactive than the chlorobenzene complex. The difference is taken as evidence for a rate-limiting attack on the arene ligand followed by fast loss of halide the concentration of the cyclohexadienyl anion complex does not build up. In the reaction of fluorobenzene-Cr(CO)3 with amine nucleophiles, the coordinated aniline product appears rapidly at 25 °C, and a carefiil mechanistic study suggests that the loss of halide is now rate limiting. 

In one case a spirocyclobutyl-substituted vinyl oxirane has been converted to an a-ethylidenecyclo-pentanone (91TL3395). Vinyl oxiranes are coupled with organostannanes in the presence of (CH3CN)2PdCl2 to furnish allylic alcohols in good yields (88JA4039,89T979). Heteroatom nucleophile... 

The nucleophilic addition on substituted ketenes is a well-known method to generate a prochiral enolate that can be further protonated by a chiral source of proton. Metallic nucleophiles are used under anhydrous conditions therefore, the optically pure source of proton must be added then (often in a stoichiometric amount) to control the protonation. In the case of a protic nucleophile, an alcohol, a thiol, or an amine, the chiral inductor is usually present at the beginning of the reaction since it also catalyzes the addition of the heteroatomic nucleophile before mediating the enantioselective protonation (Scheme 7.5). The use of a chiral tertiary amine as catalyst generates a zwitterionic intermediate B by nucleophilic addition on ketene A, followed by a rapid diastereoselective protonation of the enolate to acylammonium C, and then the release of the catalyst via its substitution by the nucleophile ends this reaction sequence. 

Various organotin compounds with tin-heteroatom bonds are synthesized by the reactions of halostannanes with the corresponding heteroatom nucleophiles. For example, trialkyltin alkoxides and trialkyltin amides are prepared by the treatments of halostannanes with sodium alkoxides (eq (139)) [134] and lithium amides (eq (140)) [135], respectively. Tin alkoxides are also formed by the reaction of alcohols with tin amides (eq (141)) [136]. 

The metal-bound carbonyl ligand is readily subjected to the attack of not only carbanions but heteroatom nucleophiles such as alcohols and amines to form ligands useful for formation of compounds containing ester and amide functionalities. The ease with which the nucleophilic attack takes place at metal-coordinated alkenes and alkynes provides a basis for oxidation of these molecules in the presence of a transition metal complex catalyst [3,4a], as exemplified by the Wacker type alkene oxidation by the use of a Pd catalyst. Metal catalyzed addition of alcohols or amines to alkenes and alkynes also involve the analogous nucleophilic attack [4b-e]. The attack of carbanions and heteroatom nucleophiles... 

Electron-withdrawing groups at C-2 have been successful in activating indoles for nucleophilic substitution chemistry. For example, loss of phenylsulfinate with the intramolecular addition of heteroatom nucleophiles to the C-3 position of indole has been demonstrated as early as 1977 [39]. This example involved the intramolecular attack of an alcohol onto C-3 of 77 with the concomitant loss of phenylsulfinate to produce a pyrido[4, 3 5,6]oxepino[3,2-b]indole 78. 

Catalytic reactions of allylic electrophiles with carbon or heteroatom nucleophiles to form the products of formal S 2 or S 2 substitutions (Equation 20.1) are called "catalytic allylic substitution reactions." Tliese reactions have become classic processes catalyzed by transition metal complexes and are often conducted in an asymmetric fashion. The aUylic electrophile is typically an allylic chloride, acetate, carbonate, or other t)q e of ester derived from an allylic alcohol. The nucleophile is most commonly a so-called soft nucleophile, such as the anion of a p-dicarbonyl compound, or it is a heteroatom nucleophile, such as an amine or the anion of an imide. The reactions with carbon nucleophiles are often called allylic alkylations. 

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