Protic nucleophiles

In order to avoid competitive bimolecular photoreactions such as ketone reduction by hydrogen abstraction, poor hydrogen donating solvents are recommended (acetonitrile, acetic acid, tertiary alcohols). In those cases where ketene trapping is desired, solvents must also be miscible with water or other protic nucleophiles. 

The relations in Scheme V take into account intranuclear and intemuclear resonance activation and the special cases of 2-Le-3-aza (poor) and 4-Le-8-aza (extremely poor) activation as well as the two groups of inductive activation the possibility of an accelerative peri effect in substitutions with protic nucleophiles is indicated by the sign for 4-Le-5-aza compounds. 

In contrast to the situation on flash pyrolysis, methyleneoxophosphoranes generated by thermolysis or photolysis in the presence of protic nucleophiles can be directly trapped to form corresponding derivatives of phosphinic acid (17- 19) however, the possibility of competing insertion of carbenes into the H/X bond of the additives is always present, giving phosphine oxides with X in the a-position (16- 18). Reaction branching at the carbene 16 was first observed on photolysis of 7 in water 13) and prompted detailed investigations on the phosphorylcarbene/ methyleneoxophosphorane rearrangement. 

In complete contrast, the photolysis of (diazomethyl)diphenylphosphine oxide completely avoids the insertion (16- 18). High yields of the corresponding phos-phinic acid derivatives (19d f) are found both in water and methanol and in the presence of morpholine (see Table 1)u,14). In general, methyleneoxophosphoranes show the same reactivity towards protic nucleophiles as other heterocumulenes. 

The regiochemistry of nucleophilic addition to alkene radical cations is a function of the nucleophile and of the reaction conditions. Thus, water adds to the methoxyethene radical cation predominantly at the unsubstituted carbon (Scheme 3) to give the ff-hydroxy-a-methoxyethyl radical. This kinetic adduct is rearranged to the thermodynamic regioisomer under conditions of reversible addition [33]. The addition of alcohols, like that of water, is complicated by the reversible nature of the addition, unless the product dis-tonic radical cation is rapidly deprotonated. This feature of the addition of protic nucleophiles has been studied and discussed by Arnold [5] and Newcomb [84,86] and their coworkers. 

The reaction is believed to begin with the metalation of the substrate via aromatic electrophilic substitution (SEAr) followed by CO insertion and nucleophilic displacement by water or another protic nucleophile such as tri-fluoroacetic acid (TFFA) to give, respectively, the aromatic carboxylic acid or its mixed anhydride derivative, from which the acid is freed by hydrolysis (Scheme 24). 

Main routes to 71-donor-substituted allenylidene complexes include (1) the nucleophilic addition of secondary amines to Fischer-type carbenes [M =C(OR ) C=CR (C0)5] (M = Cr, W) [9], (2) the Lewis-acid induced abstraction of NR2 groups from anionic complexes [M C=CC(NMe2)3](CO)5] (M = Cr, W) [9], and (3) the regioselective addition of protic nucleophiles to metallacumulenylidenes with more extended unsaturated carbon chains, such as butatrienylidenes or penta-tetraenylidenes [10]. In the following sections updated syntheses are presented by Periodic Group. 

Whereas d ruthenium complexes add protic nucleophiles to the C3=C4 of the butatrienylidene ligand to give alkenylallenylidene complexes (see Scheme 3.22), iridium complex 11 adds trifluoroacetic add to the C2=C3 bond to form an alkenylvinylidene complex [2, 3]. The corresponding reaction of 11 with two equivalents of HCl yields, presumably again via an alkenylvinylidene complex, a five-coordinate alkenyl(dichloro) complex with a trigonal-bipyramidal coordination geometry (Scheme 3.29) [3]. 

The isomeric adamantane-spirothiadiazolines (145 and 146) (Scheme 8.34) exhibit different thermal stability [145 Xi/2 = 33 min at 45 °C 146 Xi/2 = 25.6 min at 110 °C (206a)]. Elimination of N2 from 145 generates thiocarbonyl ylide 147 that was trapped not only with the dipolarophiles mentioned above for 140, but also with aldehydes and imines (206a) (147 —> 149). Without a trapping reagent, thiirane 151 was formed from both 145 (at 80 °C) and 146. In the latter case, the extrusion probably proceeds via intermediate 148 and is accompanied by homo-adamantanethione 152 and a trace of methyleneadamantane. When 145 was decomposed at 45°C rather than at 80 °C, dimer 150 was also obtained. The isolation of 150 suggests that ylide 147 is also able to act as a base toward its precursor 145 (213). In fact, 147 can also be trapped with other protic nucleophiles. 

Besides [2,3]-sigmatropic rearrangement and [l,2]-shift reactions, the oxonium ylide may undergo other reactions. The oxonium ylide intermediate can be trapped by a protic nucleophile. Oku and co-workers have developed a method for ring expansion of cyclic ethers through oxonium ylide formation. Bicyclic oxonium ylide... 

Problem 7.29 In terms of transition-state theory, account for the following solvent effects (a) The rate of solvolysis of a 3° RX increases as the polarity of the protic nucleophilic solvent ( SH) increases, e.g. 

A number of protic nucleophiles including water, 2-mercaptoethanoI, bisulfite ion, and hydroxylamine have been shown to form anionic a-adducts by reaction with l,3-dimethyl-5-nitrouracil in aqueous solution.57 These adducts have the general structure 119, which is characterized by strong absorption maxima in the range 320-326 nm (e 1-2 x 104 M 1 cm"1), involving a small bathochromic shift with respect to the substrate (Amax = 308 nm). Also, H-NMR data show a strong upheld shift of the ring proton of the order of 3.3 ppm. 

The reactions between isocyanates and protic nucleophilic reagents are characterized by an intrinsic reversibility under heating. Typical urethanes tend to decompose to isocyanate and alcohol at temperatures T 180— 250°C, depending on the substituents. In the same range of temperature or just below, exchange reactions are also possible between two urethanes ... 

Hydroperoxide 7 through reaction of Zwitterion 3 with protic, nucleophilic molecule like ROH, H20, R-COO, NHR. 

Abstract The dimerization of 1,3-dienes (e.g. butadiene) with the addition of a protic nucleophile (e.g. methanol) yields 2,7-octadienyl ethers in the so-called telomerization reaction. This reaction is most efficiently catalyzed by homogeneous palladium complexes. The field has experienced a renaissance in recent years as many of the platform molecules that can be renewably obtained from biomass are well-suited to act as multifunctional nucleophiles in this reaction. In addition, the process adheres to many of the principles of green chemistry, given that the reaction is 100% atom efficient and produces little waste. The telomerization reaction thus provides a versatile route for the production of valuable bulk and specialty chemicals that are (at least partly) green and renewable. The use of various multifunctional substrates that can be obtained from biomass is covered in this review, as well as mechanistic aspects of the telomerization reaction. 

The highly strained cycloproparenes behave in the same way in the presence of silver salts. For example, the simplest member of this family gave the benzyl ether in a protic, nucleophilic solvent within a few minutes, while in an anhydrous and nonnucleophilic solvent, such as chloroform, dimerization occurred (Scheme 3.16).30... 

However, when bound to a higher metal oxidation state center, with a limited tt-electron donor ability, the nitriles display v (N C) higher than in the free state and can be activated toward nucleophilic attack, as observed for the reactions of cfr-[ReCLi(NCMe)2] (formed by spontaneous reduction of ReCls in NCMe) with oximes, HON=CRR, amino-alkylated adenines, or alcohols, which behave as protic nucleophiles (reaction 2) to yield, for example, in the flrst case, the imine complexes cA-[ReCl4 NH=C(Me)ON=CRR 2]. 

Isocyanides, when bound to weak tt-donor metal centers, can also undergo addition of protic nucleophiles (HNu) to form aminocarbene M=C(Nu)NHR species. Hence, a parallelism of behavior is observed for nitriles and isocyanides. In both ligands, either the electrophilic or the nucleophilic addition occurs at the unsaturated atom at the jS-position that exhibits a higher reactivity than the metal coordinated terminal atom. 

To use the reaction leading to the triaminocyclopropenium ion from tetrachlorocyclopropene, which is considered to be the simplest way, seems inappropriate because the reaction of tetrachlorocyclopropene (4) with protic nucleophiles such as alcohol and water yields the ring-opened products ) as shown in Eqs. (1) and (2). 

Although addition of a nucleophile to a tt radical cation seems to be a straightforward process, several mechanistic scenarios [284] (e.g. the disproportionation, complexation, and half-regeneration pathways) that depend on the reactants need to be considered [285]. It has, moreover, been stressed that for protic nucleophiles such as alcohols and water, deprotonation of the primary adduct is important [286]. As a consequence, the rational design of bond-forming reactions requires deeper understanding of mechanistic matters. 

The second method (Route B Eq. 23) took advantage of the fact that a-lactones add protic nucleophiles at the a-carbon. Thus, hydrogen peroxide adds to a-lactones to give the desired a-hydroperoxy acids (13) in essentially quantitative yields. However, the big limitation in this route is the availability of the elusive a-lactones. Sterically hindered a-lactones that are sufficiently stable at low temperatures for preparative purposes can be made by ozonization of the respective ketenes, e.g. di-t( f-butylketene. The unstable ones, which necessarily must be prepared insitu, are now quite readily available through photodecarboxylation of malonyl peroxides. Again, the synthesis of a-hydroperoxy acids via a-lactones takes place under perfectly neutral conditions ... 

Tilborg and coworkers " recently reported an extensive study concerning the electrosynthesis of cyclopropanone adducts from either a,a -dibromo ketones or from a,a -dibromo- and a,a -dichloro-carbonyl protected ketones. With the non-protected ketones the reductions were carried out in MeCN in the presence of various nucleophiles (Table 2). It was found that the yields of cyclopropanone adducts decrease when the dihaloketone becomes less substituted, due to a competing side reaction in which a bromide is displaced by the nucleophile. Furthermore, in the presence of excess of added protic nucleophile the yields of the cyclic products decrease due to a competing protonation of the anionic intermediate. 

Addition of Na2S to the methylidene complex 307 gives rise to a trinu-clear sulfonium salt (308) (108). The action of a protic nucleophile, like H2S, on the prochiral phosphinoketene ligand in 309 (R = Me, Ph) leads to five-membered chiral metallaheterocycles (310), which are organometallic derivates of y-thiolactones (197). 

Photochemical ring opening of linearly conjugated cyclohexadienones affords dienylketenes (145), which react in one of the following ways recycli-zation to the original or to a stereoisomeric cyclohexadienone, formation of bicyclo[3.l.0]hexenones (146), or addition of a protic nucleophile to yield substituted hexadienecarboxylic acids (147) (Quinkert et al., 1979). 

The addition of a protic nucleophile to a carbocation is always followed by deprotonation of the nucleophile. 

The 7- and 6-membered metallaphosphaheterocycles (8)22 and (9)23 with bridging azavinylidene moieties, were obtained from a rare nitrile organophosphine coupling in some Mo2 acetonitrile complexes. The formation of (9) involves deprotonation of the phosphine, which behaves as an aprotic nucleophile, but an acidic phosphine can also act as a protic nucleophile (see below). 

Reactions with Protic Nucleophiles 1.34.2.2.1 Formation of C O bonds... 

Typical protic nucleophiles, like water or alcohols (R OH), readily add to nitrile ligands (Table 2), which can also be activated by coordination toward other, less common nucleophilic OH reagents, such as oximes or hydroxylamine, producing imine-type species (Scheme 2 (2)) or, in the case of water, an amidate or derivative. 

Table 2 Reactions of nitrile ligands with protic nucleophiles formation of C—O bond.

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