Tert-Alkyl esters

Fig. 6. 23. AflLl mechanism of the acidic cleavage of tert-alkyl esters.

Tert. alkyl esters. Barium ferf-butyl phosphite stirred and treated with bromine in water in the presence of Ba-hydroxide and Ba-carbonate at pH 8-9 at 20°, and the product isolated after 18hrs. barium ferf-butyl phosphate. Y 78%. F. e. s. E. Cherbuliez et al., Helv. 47, 1659 (1964). 

In peptide syntheses, where partial racemization of the chiral a-carbon centers is a serious problem, the application of 1-hydroxy-1 H-benzotriazole ( HBT") and DCC has been very successful in increasing yields and decreasing racemization (W. Kdnig, 1970 G.C. Windridge, 1971 H.R. Bosshard, 1973), l-(Acyloxy)-lif-benzotriazoles or l-acyl-17f-benzo-triazole 3-oxides are formed as reactive intermediates. If carboxylic or phosphoric esters are to be formed from the acids and alcohols using DCC, 4-(pyrrolidin-l -yl)pyridine ( PPY A. Hassner, 1978 K.M. Patel, 1979) and HBT are efficient catalysts even with tert-alkyl, choles-teryl, aryl, and other unreactive alcohols as well as with highly bulky or labile acids. 

One of the interesting application of 12 (R= allyl, X=Br) will be the synthesis of cyclic amino acid, (S)-pipecolic acid, as its tert-butyl ester 271251 Monoalkylation of the O Donnell imine 23 with l-chloro-4-iodobutane afforded the alkylated product 26 with 99 % ee. The conversion of 26 to the tert-butyl ester of pipecolic acid 27 was achieved in high yield by the sequence imine reduction, cyclization, and hydrogenolytic removal, as shown in Scheme 8. 

The use of chiral auxiliaries has been developed into elegant three-step sequences to achieve high ee s (Figure 2). In the general scheme a ketone is derivatized with a chiral amine. Low temperature lithiation and alkylation followed by hydrolysis produces the alkylated ketone in moderate to excellent ee s. The auxiliaries most often used are (S)-valine tert-butyl ester (Koga), l-amino-2-methoxymethylpyrrolidine (Enders) and (S)-2-amino-1-... 

Preparation of 0-Allyl-N-(9)-anthracenylmethylcinchonidinium Bromide as a Phase Transfer Catalyst for the Enantioselective Alkylation of Glycine Benzophenone Imine tert-Butyl Ester. 

Enantioselective Alkylation of Glycine Benzophenone Imine tert-Butyl Ester. 

Jew, Park and coworkers performed systematic investigations to develop a more efficient system for the asymmetric synthesis of a-alkylalanines by chiral phase-transfer catalysis [31]. Eventually, sterically more demanding 2-naphthyl aldi-mine tert-butyl ester 14 was identified as a suitable substrate, and its alkylation in the presence of stronger base rubidium hydroxide (RbOH) and 0(9)-allyl-N-2, 3, 4 -trifluorobenzyldihydrocinchonidinium bromide (6a) at lower reaction temperature led to the highest enantioselectivity (Scheme 2.11). 

The group of Jew and Park successfully utilized dihydrocinchonidine-derived 6f as an efficient catalyst for the asymmetric alkylation of o-biphenyl-2-oxazoline- and o-biphenyl-2-thiazoline-4-carboxylic acid tert-butyl esters (16a and 16b) under mild solid-liquid phase-transfer conditions (Scheme 2.13) [32,33]. These reactions are... 

Having optimized the catalytic enantioselective phase-transfer alkylation system, the group explored the scope and limitations. A variety of electrophiles were reacted with the benzophenone imine glycine tert-butyl ester 1 catalyzed by 5 mol% of the selected chiral dimeric PTCs, benzene-linked-l,3-dimeric PTC 37, 2 -F-benzene-linked-1,3-dimeric PTC 41, and naphthalene-linked-2,7-dimeric PTC 39, at reaction temperatures of 0°C or — 20 °C (Scheme 4.8). 

In 1999, in consideration of the readily structural modifications and fine-tuning of catalysts to attain sufficient reactivity and selectivity, Maruoka and coworkers designed and prepared the structurally rigid, chiral spiro ammonium salts of type 1 derived from commercially available (S)- or (R)-1,1 -bi-2-naphthol as a new C2-symmetric chiral phase-transfer catalyst, and successfully applied this to the highly efficient, catalytic enantioselective alkylation of N-(diphenylmethylene)glycine tert-butyl ester under mild phase-transfer conditions (Scheme 5.1) [7]. 

The salient feature of le as a chiral phase-transfer catalyst is its ability to catalyze the asymmetric alkylation of glycine methyl and ethyl ester derivatives 4 and 5 with excellent enantioselectivities. Since methyl and ethyl esters are certainly more susceptible towards nucleophilic additions than tert-butyl ester, the synthetic advantage of this process is clear, and highlighted by the facile transformation of the alkylation products (Scheme 5.3) [8],... 

With bis(3,4,5-trifluorophenyl)-substituted catalyst (S)-16A, the substituent effect of R was examined by changing the number of straight alkyl chains (Figure 5.1). In the asymmetric benzylation of N-(diphenylmethylene)glycine tert-butyl ester 2, use of (CH3(CH2) ,1)2NH (n > 4) gave a uniformly high asymmetric induction. 

The chiral phase-transfer catalysis of le was further applied to the facile synthesis of L-Dopa ester and its analogue, which usually have been prepared by either asymmetric hydrogenation of eneamides or enzymatic processes, and tested as potential drugs for the treatment of Parkinson s disease. Phase-transfer-catalyzed alkylation of 2 with the requisite benzyl bromide 35a in toluene-50% KOH aqueous solution proceeded smoothly at 0 °C under the influence of (R,R)-le to furnish fully protected L-Dopa tert-butyl ester this was subsequently hydrolyzed to afford the corresponding amino ester 36a in 81% yield with 98% ee. Debenzylation of 36a under... 

A biphenyl and ct-methylnaphthylamine-derived chiral quaternary ammonium salt 23d, which was shown by Lygo to be effective for the asymmetric alkylation of Schiffs base 20, was also effective in the Michael reaction (Scheme 7.12) [43]. Notably, the enantioselectivity was highly dependent on the reaction conditions and substrates used. The Michael reaction of imine esters such as benzhydryl and benzyl esters with a,p-unsaturated ketones under solid-liquid phase-transfer catalysis conditions afforded the Michael adduct in up to 94% ee and 91% ee, respectively, while the tert-butyl ester showed moderate enantioselectivity (Scheme 7.12). Interestingly, in contrast to earlier reports, acrylate [42] and acrylamides failed to undergo the Michael reaction under these optimized conditions. 

---