Reactivity phase-transfer benzylation

Table 5.1 Effect of catalyst structure, solvent and aqueous base on the reactivity and selectivity of phase-transfer benzylation of 2. 

The phase-transfer benzylation of 2 with the catalyst (S)-12a having [1-naphthyl group on the 3,3 -position of the flexible biphenyl moiety proceeded smoothly at 0 °C to afford the corresponding alkylation product (R)-3 in 85% yield with 87% ee after 18 h. The origin of the observed chiral efficiency could be ascribed to the considerable difference in catalytic activity between the rapidly equilibrated, diaste-reomerichomo- and heterochiral catalysts namely, homochiral (S,S)-12a is primarily responsible for the efficient asymmetric phase-transfer catalysis to produce 3 with high enantiomeric excess, whereas the heterochiral (R,S)-12a displays low reactivity and stereoselectivity. 

It has also been found that the 3-OH group is the least reactive of the hydroxyl groups in lactose under many reaction conditions (Scheme 3.33). Accordingly, direct benzoylation of lactose yielded the 3-OH derivative in 24% crystalline yield [7], tin activated benzoylation of TMSE (3-lactoside gave 85% of the 3-OH lactoside [57] and phase-transfer benzylation of benzyl lactoside produced 26% of the corresponding 3-OH compound [39]. 

Palladium complexes also catalyze the carbonylation of halides. Aryl (see 13-13), vinylic, benzylic, and allylic halides (especially iodides) can be converted to carboxylic esters with CO, an alcohol or alkoxide, and a palladium complex. Similar reactivity was reported with vinyl triflates. Use of an amine instead of the alcohol or alkoxide leads to an amide. Reaction with an amine, AJBN, CO, and a tetraalkyltin catalyst also leads to an amide. Similar reaction with an alcohol, under Xe irradiation, leads to the ester. Benzylic and allylic halides were converted to carboxylic acids electrocatalytically, with CO and a cobalt imine complex. Vinylic halides were similarly converted with CO and nickel cyanide, under phase-transfer conditions. ... 

General.—The relatively unreactive diethyl arylmethylphosphonates have been used quite successfully in alkene synthesis with phase-transfer catalysis.100 In a comparative study it was shown that anions derived from /S-ketophosphonamides (109) have very low reactivity whereas those from 0-ketophosphonates (110) react quite well with aldehydes to give frwjj-alkenes.101 Benzyl dimethyl phosphonoacetate (111) can be used to form alkenes, e.g. (112), from which the benzyl group can be removed by hydrogenolysis without disturbing the C=C bond.102 The carbanions (113) can be... 

Scheme 17 illustrates enantioselective synthesis of a-amino acids by phase-transfer-catalyzed alkylation (46). Reaction of a protected glycine derivative and between 1.2 and 5 equiv of a reactive organic halide in a 50% aqueous sodium hydroxide-dichloromethane mixture containing 1-benzylcinchoninium chloride (BCNC) as catalyst gives the optically active alkylation product. Only monoalkylated products are obtained. Allylic, benzylic, methyl, and primary halides can be used as alkylating agents. Similarly, optically active a-methyl amino acid derivatives can be prepared by this method in up to 50% ee. 

Under solid-liquid phase-transfer conditions, amino adds 17 and 25a,b were obtained from reactions using benzyl bromide, allyl bromide and 1-chloromethylnaphthalene, respectively, as the alkylating agents in the presence of 10 mol% of (S)-Nobin. Products 17 and 25a were obtained with >90% yield and 67-68% ee, whilst product 25b was obtained in only 60% yield and with only 18% ee, presumably due to the lower reactivity of the benzylic chloride-based alkylating agent. 

Neighboring group participation is also another important factor for predicting the reactivity of secondary hydroxyl groups, particularly at the C-2 position. Under basic conditions, the C-2 hydroxyl tends to be more acidic than the C-3 hydroxyl and this may be advantageously exploited in certain cases such as partial benzylation under phase-transfer catalysis. The latter reaction conditions also contribute to the relatively good selectivity for substitution at a primary hydroxyl group in preference to a secondary one at either C-3 or C-4. 

Alkylation of tosylmethylisocyanide. Tosylmethylisocyanide (4, 514-516 5, 684-685) can be monoalkylated in high yield (75-95%) by primary alkyl halides (including alkyl chlorides and benzyl bromide) under phase-transfer conditions with either this quaternary salt or the less reactive benzyltriethyl-ammonium chloride. Yields are lower with secondary alkyl halides. With more reactive alkyl hahdes, the reaction is conducted at 0° to avoid dialkylation. 

Similar trends were seen in a study of N1 versus C3 alkylation of indole under phase transfer conditions. These conditions involve a weakly coordinating counterion so that iV-alkylation should be preferred. Benzyl chloride gives a higher N C ratio than benzyl bromide, reflecting the generalization that more reactive alkylating agents will tend to favor C-alkylation <90H(31)447>. 

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