Nucleophile phenol

While the efficacy of these new, biologically active materials has been attributed (28,29) primarily to the presence of the fluoroalkoxy group, it is important to note that the need for more efficient syntheses of these and related materials still exists. For example, the syntheses of both the above materials involve multi-step, moderate yield processes in which the fluoroalkoxy group is introduced in the initial step of the sequence via reaction of a nucleophilic phenolate derivative with either a fluoroalkene ( ) or a triflate... 

The synthetic utility of ion exchange resins in combinatorial chemistry has been demonstrated by the use of a basic polymeric base PTBD (l,5,7-triazabicydo[4.4.0]dec-5-ene) 26 in a series of O- and N-alkylation experiments (Scheme 7) [15]. For example, deprotonation of the phenol 27 with this polymeric base PTBD 26 gave the ionic polymeric species 28 which contained the more nucleophilic phenolate. Addition of the 2-bromo aryl ketone 29 gave the aryl ether 30 in reasonable yield and in high purity (Scheme 7). The basic polymeric scavenger PTBD 26 removed all the unwanted HBr produced within the reaction mixture (in the form of 31) and advantageously eliminated the need for an aqueous extractive work-up procedure. 

Finally, in the PDO preparation through the Beirut reaction, the reactivity of the phenol is very important to the success of the process. For example, less nucleophilic phenol, like p-formylphenol dioxalane, does not conduct to the desired product [45]. 

In contrast, reaction of electron acceptor-substituted phenols exhibits p = +1.72, indicating the development of negative charge at the phenolic oxygen in the rate-determining step for reaction of relatively acidic, weakly nucleophilic phenols with 110, and the addition of 112f exhibits a large primary deuterium kinetic isotope effect of k /kv = 5.3. This is consistent with the electrophilic addition mechanism of equation 85, in which full or partial protonation at silicon precedes nucleophilic attack. 

The connection of adjacent phenolic units by directional bridges may be mentioned as an additional possibility. The C2-symmetrical lactone 102a is obtained in 36% yield from the tetrachloromethylated calix[4]arene tetrapropyl ether by reaction with salicylic acid. The formation of the Cs-symmetrical isomer is not observed in this case, probably since the most nucleophilic phenolate attacks at opposite rings, due to a pinched cone conformation of the tetrapropyl ether.196 In contrast, the similar cyclization with 3-hydroxymethyl-2-naphthol gave mainly the Cs isomer (Cs/C2 = 95/5). However, the C2 isomer 102b could be isolated and has been resolved by enantioselective HPLC (Chiralpak AD, a = 3.17).145... 

These internal salts are stabilized by hydration. Removal of the water of crystallization causes polymerization. The nucleophilic phenolic anion attacks the a carbon of the sulphonium ion, generating a linear chain... 

The nucleophilic phenolate oxygen atom of 3-27 adds to the carbon of the thioester group then ethylthiolate is eliminated. 

The intermediate, 4-82, can decompose to give a new electrophile, with Problem 4.17 which the nucleophilic phenol then reacts. continued... 

Scheme 3-54). This transformation constitutes a cascade of an intramolecular Heck insertion and subsequent heterocyclization. The initially formed arylpalladium species attacks the bridgehead position of the diene functionality in 238 to foim a JT-allylpalladium complex which is trapped by the internal nucleophilic phenol moiety (cf. Scheme 3-26). Since the starting diene 238 can be prepared in both enantiomeric forms by asymmetric reduction of a ketone, this sequence allows the preparation of both the natural morphine and its unnatural enantiomer. 

An efficient regio- and stereoselective organometalUc method to nucleophilic phenol ortljo-lhnctionahzation promoted by a cyclopentadienyl iridium cation ([Cp Ir] +, where Cp is CsMes) was reported by Amouri and coworkers (equation 47) (the electrophilic phenol Ihnctionalization by means of electron-rich moiety [Os(NH3)5] was mentioned above , see Section n.A.4). 

Allylic alkylations. Highly regiosi nucleophiles (phenolates, sulfonamides, ami also possible with the Rh catalyst modiho seems to play an important role in the di branched allylic ethers thus, reaction with 1 the product yields are low. The best comprot... 

Amino acid residues, except hydrocarbon chains, may provide nucleophilic sites (electron-rich centers) or electrophilic sites (electron-deficient centers) for chemical modifications. Electron-rich centers include sulfur nucleophiles (thiol of Cys and thioether of Thr), nitrogen nucleophiles (e-amino of Lys, imidazole of His and Guanidyl of Arg), oxygen nucleophiles (phenolic of Tyr, carboxyl of Asp and Glu and hydroxyl of Ser and Thr), and carbon nucleophile (a-position of indole ring of Trp), with an increasing nucleophilicity in that order. They provide nucleophilic sites for alkylation (nncleophilic substitution), acylation, addition and oxidation at pH near or above their pK values. Electron-deficient centers include ammonium cation of Lys, guanidiiun cation of Arg and imidazolium cation of His. They provide electrophilic sites for metalation and reduction at pH near or below their pK values. 

Alkoxyisocyanates. Methanol and 4-5 drops of triethylamine added to a soln. of startg. carbodiimide in benzene, heated at 80" for 8-10 h, and worked up after removal of the corresponding amide (Y 86-92%) at 5-10° - product. Y 58%. F.e. and nucleophiles (phenols, thiophenols, imines), also reaction with water and /cr/-butyl-amine, s. M.V. Vovk et al., Zh. Org. Khim. 24, 727-32 (1988) 1,1-acoxyisocyanates s. ibid. 1237-40. 

In the course of these investigations, an interesting dependence on the Pd-ligand was disclosed. In contrast to alcohols such as 310, where the best results were obtained with bisdentate aromatic phosphines, one had to change to monodentate Hgands in the case of the less nucleophilic phenols [99]. 

Much less work has been devoted to optimizing polyester formation. However, diols also react with aromatic diiodides and CO to form polyesters of modest molecular weight (equation 7). Longer reaction times are needed for the much less nucleophilic phenol (compared to the aniline derivatives), which allows more time for chain-limiting side reactions to occur (20). 

---