J . O r g . Chem. 1994,59, 7259-7266
7269
Scope and Mechanism of Deprotection of Carboxylic Esters by Bis(tributy1tin) Oxidel Claudio J. Salomon, Ernest0 G. Mata, and Oreste A. Mascaretti* Instituto d e Quimica Organica d e Sintesis (CONICET- U N R ) Facultad d e Ciencias Bioquimicas y Farmackuticas, Casilla d e Correo 991, 2000 Rosario, Argentina Received February 25, 1994 (Revised Manuscript Received September 26, 19943
Methyl and ethyl esters of aliphatic and aromatic carboxylic acids as well as benzyl carboxylates, thiol esters and double esters such as (pivaloy1oxy)methyl carboxylates have been successfully cleaved with bis(tributyltin1 oxide to give the free carboxylic acids in good yields. The reaction is carried out in aprotic solvents under essentially neutral conditions and thus this method can serve as an ideal procedure for the cleavages of esters with other functional groups a n d o r protecting groups acid and/or base sensitive. We demonstrated t h a t the reaction displays a high level of chemoselectivity between methyl and ethyl esters versus tert-butyl esters and y-lactones. Bis(tributyltin) oxide is also a highly efficient reagent for the cleavage of acetates of primary and secondary alcohols and phenols. The limitations we found in the use of this reagent include the lack of cleavage of esters sterically hindered around the carboxyl carbon and the carbinol group (i.e., esters of tertiary alcohols) and in carboxylic esters t h a t contain a fluoroalkyl substituent. A resonable mechanistic explanation is discussed to account for the reaction pathway of the acyloxygen cleavage of (-)-(LR)-menthyl acetate.
Introduction Soft nucleophilic
Developing efficient and mild methods for the selective cleavage of carboxylic esters to afford the carboxylic acids continues to be a significant aspect of experimental organic chemistry. We recently2s3 have developed a simple and effective, non-hydrolytic method for the cleavage of simple carboxylic esters, such as methyl, ethyl, phenacyl, and phenyl esters, as well as for the deprotection of double esters, such as (pivaloy1oxy)methyl esters, by the action of bis(tributy1tin) oxide’ (henceforth abbreviated BBTO). Since a carboxylic ester possesses a hard center (carboxyl carbon) and a soft center (carbinol carbon), using the principles of hard/soft acid base t h e ~ r y , hard ~ , ~ nucleophiles are predicted to show a preference for attack on the carboxy carbon (hard-hard interaction) rather than the carbinol carbon (hard-soft interaction) (Figure 1). In evaluating the various hard nucleophiles which are available, “naked” fluoride anion6 is one choice. Similarly, pertinent internal bifunctional systems conin Advance ACS Abstracts, November 1, 1994. (1)The naming of organotin compounds follows the trivial system by using “tin” as a suffix, as in: Pereyre, M.; Quintard, J. P.; Rahm, A.Tin in Organic Synthesis; Butterworths: London, 1987;p 3. (2)Mata, E.G.;Mascaretti, 0. A. Tetrahedron Lett. 1988,29,6893. (3)Salomon, C.J.;Mata, E. G.; Mascaretti, 0. A. Tetrahedron Lett. 1991,32,4239. (4)(a)Pearson, R. G. J.Am. Chem SOC.1963,85,3533. (b) Hudson, R.F.Coordination Chemistry Reviews 1966,89.(c) Saville, B. Angew. Chem., Znt. Ed. Engl. 1967,6,928.(d) Pearson, R.G.; Songstad, J. J. Am. Chem. SOC.1967,89,1827. (e) Pearson, R. G.; Songstad, J. J.Org. Chem. 1967,32,2899.(0 Parr, R. G.; Pearson, R. G. J.Am. Chem. SOC.1983,105,7512.(g) Pearson R.G. J. Am. Chem. SOC.1988,110, 7684.(h)Pearson, R. G. J. Org. Chem. 1989,54,1423.(i) Pearson, R. G. Acc. Chem. Res. 1993,26,250. ( 5 ) For a review see: (a) Pearson, R. G. Hard and Soft Acids and Bases; Dowden, Hutchinson, & Ross Inc.: Stroudsberg, 1973.(b)Ho, T. L. Hard and Soft Acids and Bases Principle in Organic Chemistry; Academic Press: New York, 1977.(c) Ho, T. L. Chem. Rev. 1976,75, 1. ( 6 )The only unsolvated (“naked”)fluoride anions that have proven reliable are tetramethylammonium fluoride, phosphazenium fluoride, fluoride, see: (a) Masand N,N,N-trimethyl-1-adamantylammonium caretti, 0. A. Aldrichimica Acta 1993,26, 47. (b) Harmon, K. M.; Southworth, B. A.; Wilson, K. E.; Keefer, P. K. J. Org. Chem. 1993, 58,7294. e Abstract published
reagents r
PhS’ PhSeHTe’ X
I’ (Me3Sil) SHR I AIBr, SR2I AIBr3 Br- (MgBr,)
Bra (catechol Hard electrophilic center
boron bromide)
Figure 1.
sisting of a hard acid and a hard nucleophile should attack the carboxylic ester at the carboxy center rather than at the carbinol center and, therefore, accomplish acyl-oxygen cleavage without affecting the stereochemistry of a chiral center at the carbinol carbon. On the other hand, the alternative approach of cleaving esters via nucleophilic attack at the carbinol carbon under non-hydrolytic conditions in non-hydroxylic solvents can be employed. Thiophenoxide, alkanethiolate, trithio-carbonate, ethanedithiolate, sulfide, phenyl selenide, hydrogen selenide, and telluride anions are representative of the soft nuclephile class. Besides, the most widely used combination systems, consisting of a hard acid and a soft nucleophile, are: trimethylsilyl iodide, aluminium halide-ethanethiol, aluminium halidedialkyl sulfide, aluminium triiodide, magnesium bromide, magnesium iodide, and catechol boron bromide. In a recent review7 we provided an update on methods for (7)Salomon, C.J.;Mata, E. G.; Mascaretti, 0.A. Tetrahedron 1993, 49,3691.
QQ22-3263/94l1959-7259$Q4.5Q/Q 0 1994 American Chemical Society
J. Org. Chem., Vol. 59,No. 24, 1994
7260
Salomon et al. Table 1. Selected Methyl and Ethyl Carboxylic Esters
Chart 1
wC02R PhJ/o2R
B rH3C y H c8o 2 R 1 R=CH3 2 R=H
3 R=CH3 4 R=H
7 R=CH3 8 R=H
9 R=CH3 10 R = H
A23
0
OR
O
5 RzCH2CH3 6 R=H
11 R = C H 3 12 R = H
HsC2-S H&-
St C O 2 R
(->C02R
x 13 R = CHzCH3 14 R = H
15 R = CH2CH3 16 R = H
17 R=CH2CH3 18 R = H
21 R = C H 3 22 R = H
23 R = C H 3 24 R = H
0
19 R=CH3 20 R = H
chemical deprotection of carboxylic esters. One cannot expect a single reagent to fullfill all the requirements for the cleavage of esters of different kinds. Currently a wide range of other non-hydrolytic methods are also available; among which hydrogenolysis, catalytic transfer hydrogenation, and nucleophilic substitution of allylic systems activated with Pd", are the most widely used.7 Whatever strategy is chosen for the nucleophilic cleavage of carboxylic esters, the mechanistic implications have to be considered along with the steric hindrance around the carbinol and carboxy carbons and the chemical properties and drawbacks of each reagent. In 19882 and 19913we reported preliminary details of our studies on the applicability of BBTO, a combination of a hard acid and a hard nucleophile, for the cleavage of a variety of carboxylic esters. In this paper we provide additional insight into (a) the selectivity of BBTO in the presence3 of a variety of functional groups, and (b) the scope and limitations of this method relative to other ester acyloxygen and alkyl-oxygen cleavage processes in the literature.
Results and Discussion I. Cleavage of Simple Alkyl Esters. To test the generality of the procedure for the cleavage of primary alkyl carboxylic esters, we have carried out the reaction on a variety of methyl and ethyl esters of aliphatic and aromatic carboxylic acids containing representative functional groups (Chart 1). The results are summarized in Table 1. Note that the procedure seems to be generally applicable for the conversion of primary alkyl carboxylic esters into carboxylic acids in good yields and the reagent BBTO is tolerant of a large range of functional groups including lactones, alkenes, cyclic ketals, acyclic and cyclic dithioketals, and vinyl bromides. It is particularly noteworthy that treatment of methyl (6')-(+)-5-oxo-tetrahydro-2-furoate (23)with BBTO in
entry
starting ester
1 2 3 4 5 6 7 8 9 10 11 12
1 3 5 7 9 11 13 15 17 19 21 23
yieldC productu
condnsb
(%I
2 4
toluene, reflux, 48 h benzene, 80 "C, 24 h toluene, reflux, 48 h toluene, 80 "C, 10 h benzene, 80 "C, 13 h toluene, 80 "C, 10 h toluene, 80 "C, 10 h toluene, 80 "C, 10 h toluene, 80 "C, 10 h toluene, 80 "C, 10 h benzene, 80 "C, 24 h acetonitrile, 60 "C, 24 h
60 90 42 70 95 48 70 52 52 80 85 55
6 8 10 12 14 16 18 20 22 24
All products gave satisfactory lH and 13CNMR spectral data. See the Experimental Section for procedures. Yields are based on pure isolated material.
acetonitrile at 60 "C for 24 h led to the (S)-(+)-~-OXOtetrahydro-2-hroic acid (24). A similar chemoselectivity was reported by Yamamoto and co-workers for the hydrolysis of methyl (R)-5-oxo-tetrahydro-2,3 dimethyl2-furoate with lithium hydroxide.8 The optical purities of acids 2, 12, and 24 were completely retained. An advantage of the BBTO-induced cleavage of esters over the traditional saponification is that the ester is not exposed to strong base. Methyl and ethyl esters are commonly encountered in organic synthesis because the particular advantage of these types of esters lies in their simple and easy preparation? Recently, methyl and ethyl as well as other alkyl carboxylates have been prepared in good to excellent yields by reaction of tributyltin carboxylates, obtained by heating an equimolecular mixture of carboxylic acid and BBTO in refluxing benzene, with alkyl halides in the presence of CsF.l0 The significance of the synthetic versatility of BBTO lies in the fact that it is possible to mask carboxylic acids temporarily as methyl or ethyl esters in the course of a multistep synthesis of polyfunctional molecules and then selectively deprotect these esters in the presence of diverse functional groups under mild conditions. Another aspect of this method is that the reaction is carried out under essentially neutral conditions and thus can serve as an ideal procedure for the cleavage of esters of acid and/or base sensitive compounds. II. Cleavage of Sterically Hindered Esters around the Carboxyl Carbon and Carbinol Carbon. In the present study, we have examined the viability of the BBTO cleavage reaction with sterically hindered methyl esters around the carboxyl carbon. Also, to achieve a n understanding of the effects of steric hindrance on the carboxyl versus the alcohol; we selected acetates of primary, secondary and tertiary alcohols (Chart 2). Examination of Table 2 shows that BBTO did not cleave the methyl esters of pivalic acid (25))0-methylpodocarpic acid (27) and 1-adamantanecarboxylic acid (28). Furthermore, when methyl l-adamantaneacetate (30)was treated with BBTO under similar conditions, the reaction was not complete, giving only 25% of 1-adamantaneacetic acid (31). By contrast, the phenylselenide induced cleavage a t the carbinol center of the hindered methyl esters (8) Yamamoto, Y.; Maruyama, IC;Komatsu, T.; Ito, W. J . Org. Chem. 1986,51,886. (9) Greene, T. W.; Wuts, P. G . M. Protective Groups in Organic Synthesis; J. Wiley & Sons: New York, 1991. (10)Sato, T.; Otera, J.; Nozaki, H. J. Org. Chem. 1992,57,2166
J. Org. Chem., Vol. 59, No. 24, 1994 7261
Deprotection of Carboxylic Esters by BBTO
Chart 2
Table 4. Selective Cleavage of Methyl and Ethyl Esters in the Presence of tert-ButylEsters
OCH3
I
e n t w starting ester product
A
B
22 23 a
C02CH3 25 R=CH3 26 R = H
27
*U
@ 32 33 34 35 36 37
R=C02CH3 R=H R = CH2C02CH3 R=CH2C02H
28 29 30 31
jhoR m
R = CH2CH20COCH3 R=CH2CH20H R = CH2OCOCH3 R=CH20H R=OCOCH3 R=OH
42 R=CH3
"
"
0
R
CH(CH~)~
38 R = COCH3 39 R = H
40 R = COCH, 41 R = H
44 R=CHzCHs 45 R = H
43 R = H
Table 2. Methyl Carboxylic Esters Sterically Hindered around the Carboxyl Carbon entry
starting ester
13 14
26 27
26
B
no reaction
tolueneiDMF, 80 "C,96 h
15 16
28 30
29 31
B B
a
product
condnsb
yield" (%)
5 10 25
Isolated yields. B: toluene, reflux, 72 h.
Table 3. Acetates of Primary, Secondary, and Tertiary Alcohols entry starting ester product 17 18 19 20 21 a
32 34 36 38 40
33 36 37 39 41
condnsb
E E E toluene, 110 "C, 24 h
E
yielda (%) 97 97 15 70 13
Isolated yields. E: acetonitrile, 90 "C, 96 h.
25 and 27 afforded the corresponding carboxylic acids in excellent yields.ll The results in Table 3 indicate t h a t the cleavage of acetate of primary alcohol 32 and primary neopentyl34 were accomplished almost quantitatively. Whereas, when this reaction was used to cleave the tertiary 1-adamantyl acetate (36), the yield was considerably lower (15%) than that obtained from 1-adamantylethyl and adamantylmethyl acetates. A comparison of the results obtained with acetates of secondary alcohols 38 and 40 also reveals the role of the steric hindrance. (11) Liotta, D.; Sunay, U.; Santiesteban, H.; Markiewicz, W. J.Org. Chem. 1981,46, 2605.
42
44
43 45
condns
yield" (%)
toluene, 80 "C,24 h toluene, 104 "C, 3 h
70 47
Isolated yields.
A comparison of the results obtained in Tables 2 and 3 reveals the difference in reactivity of 30 compared with 34 and leads to the conclusion t h a t steric hindrance a t the carboxyl inhibits the reaction more than steric a t the carbinol center. I t was apparent that this difference in reactivity could be exploited for the chemoselective deprotection of primary alkyl esters in the presence of tertiary alkyl esters. The results of this strategy are summarized in Table 4. The chemoselectivity of BBTO towards carboxylic diesters was found to be excellent. The reagent selectively cleaved the methyl ester of tert-butyl methyl succinate (42) and the ethyl ester of tert-butyl ethyl malonate (441, in the presence of the tert-butyl ester group in 70% and 47%12 isolated yield. None of the methyl succinate half ester or succinic acid and ethyl malonate half ester or malonic acid was seen within the limits of detection by lH NMR (
