Selectivity, 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. 

Ferrate salts have been used under phase-transfer catalytic conditions for the oxidation of alcohols. Selective oxidation of allylic and benzylic alcohols to the corresponding aldehydes occurs under mild conditions [4],... 

As the precursor for the B unit, the selectively benzylated -fucal derivative 75- could be obtained crystalline from L-fucal by applying a phase-transfer-catalyzed process T64). By a Ferrier reaction of di-O-acetyl-L-rhamnal and a subsequent retro enol ether formation trough hydride attack at C-3 (71.) the -amicetal 72 was obtained (64) this reaction was concurrently also es-cribed by others (72). 

When benzyl 6-0-trityl-a-D-mannopyranoside was allowed to react with allyl bromide under phase-transfer catalysis, the 3-allyl and 2-allyl ethers and the starting material were obtained in yields of 36%, 23%, and 24%, respectively [152]. The absence of the protective group at C-4 might be responsible for this difference in selectivity. 

The anionic form of 5-chloropyrimidin-2( 1 H)-one, particularly under phase-transfer conditions, was selectively methylated and benzylated at... 

Saturated and a, -unsaturated esters (cf. II, 176). The reagent is alkylated under phase-transfer conditions selectively at the y-positi in by primary or secondary alkyl iodides and by benzylic or allylic bromides. The products are convertible into saturated and unsaturated esters. 

With only minor modifications it is possible to prepare a selective oxidant for benzylic alcdiols benzyltiiethylammonium chlorochromate under phase transfer conditions exhibits such a preference. The preparation of benzyltiiethylammonium chlorochromate had been reported previously, but was initi ly assigned as the dichromate. It was demonstrated that this reagent (chromate or dichromate) shows good selectivity for benzylic and allylic alcohols, but unfortunately it was necessary to peifcwm the oxidation in HMPT. 

Another methodology applied to the monosubstitution of diols is the use of copper complexation of dianions. The dianion is first formed by reaction of a diol with two equivalents of NaH. The copper complex is then formed by addition of a copper salt. Reaction of the copper complex with various electrophiles (alkyl halides, acyl chlorides) then gives the selectively protected products. As with the phase-transfer technique, very little disubstitution is observed. However, as illustrated in Scheme 3.16, the regioselectivity is reversed (i.e., 4,6-diols give mainly 4-substitution and 2,3-diols give mainly 3-substitution). Using this technique, both alkylations (benzylation, allylation) and acylations (acetylation, benzoylation, pivaloylation) have been carried out. As usual, the degree of selectivity depends on reaction conditions and structural factors [44]. 

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. 

Catalyst I, containing the small tetrapropyl ammonium ion, was insoluble in the reaction medium during the epoxidation, so both the conversion and selectivity were low, only 60.6% and 60.2%, respectively. Catalyst A is a reaction-controlled phase-transfer catalyst with high catalytic activity and selectivity. Although catalyst 11 also has good catalytic performance, it was totally soluble in the reaction system during and after the epoxidation, because it contains a big octadecyl benzyl methyl ammonium ion. This makes catalyst recovery difficult. 

The first example of a fully recyclable fluorous chiral metal-free catalyst was reported by Maruoka and coworkers, who described the enantioselective alkylation of a protected glycine derivative (Scheme 5.17) with various benzyl- and alkyl bromides, in the presence of the quaternary ammonium bromide 62 as a phase-transfer catalyst [77]. Reactions were performed in a 50% aqueous KOH/toluene biphasic system in which 62 was poorly soluble. Nevertheless, the alkylated products were obtained in good yields (from 81 to 93%), with enantioselectivity ranging from 87 to 93% ee. Catalyst 62 was recovered by extraction with FC-72, followed by evaporation of the solvent, and could be used at least three times without any loss of activity and selectivity. 

Solid-liquid phase transfer without solvent was reported for a prochiral acceptor reaction. In the presence of M-(p-methoxyphenylmethyl)ephedrinium salt, aminomalonate underwent addition to 13 giving (S)-39 in 76% ee [33,34,35]. The selectivity was higher in the absence of solvent than in toluene or chloroform. Introduction of the electron-donating group at the M-benzyl arene moiety enhanced the selectivity. A Jt-Jt interaction between 13 and the aromatic ring of the catalyst was suggested, since the enantiomeric excesses correlated with the Hammett s factor. 

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