3321
J. Org. Chem. 1989, 54, 3321-3324
Application of (Chloromethy1)aluminum 2-(2-Propenyl)anilidein the Conversion of y- and &Lactones into Protected Hydroxy Acids Anthony G. M. Barrett,* Barend C. B. Bezuidenhoudt, Dashyant Dhanak, Alan F. Gasiecki, Amy R. Howell, Albert C. Lee, and Mark A. Russell Department of Chemistry, Northwestern University, Evanston, Illinois 60208 Received January 11, 1989
A series of y- and &lactones including several aldonolactones were reacted with (chloromethy1)aluminum 2-(2-propenyl)anilide to produce the Corresponding hydroxy amides. Protection using [ (trimethylsilyl)ethoxy]methyl chloride, (2-methoxyethoxy)methyl chloride, methoxymethyl chloride, tert-butyldimethylsilyl chloride, or tert-butyldiphenylsilyl chloride followed by ozonolysis gave the protected N - ( y -or 6-hydroxyacy1)indole derivatives. Mild saponification gave indole and the acetal- or silyl-protected hydroxy acid.
Introduction Recently, we needed a method to convert a y-lactone into a protected a-hydroxy carboxylic acid chloride or related reactive acylating reagent. Unfortunately this apparently trivial process is often difficult to carry out.'V2 For example, the attempted derivatization of y- or 6-hydroxy acids frequently results in relactonization rather than hydroxyl protection. In contrast y- or &hydroxy amides are much more reluctant to lactonize due to the reduced electrophilicity of the amide carbonyl. Thus, we sought to develop an experimentally simple and general procedure to prepare protected hydroxy carboxylic acids via amide intermediates. It is clear in such an approach that, subsequent to hydroxyl derivatization, the amide carbonyl should be activated to facilitate hydrolysis. Barton and co-workers3have demonstrated that carboxylic acids may be protected as acylhydrazines or -hydrazones. Deprotection was affected via oxidation and hydrolysis of the resultant more electrophilic acyl diazonium salt or an equivalent species. Additionally, Barton showed that acylpyrazolines, -imidazolines, -indolines, etc., were more readily hydrolyzed following oxidation of the nitrogen substituent to produce the corresponding heteroaromatic ring system. Although the acylhydrazine and hydrazone protection strategy was applied in cephalosporin synthesis, the "latent" heteroaromatic protective groups were not applied to demanding synthetic problems. Herein we report experimental details4 on the use of 2-(2-propenyl)anilides as latent equivalents for acylindoles and thereby as carboxylic acid protecting group^.^ Results and Discussion The saccharinic acid lactone l6was converted via isopropylide formation, sodium borohydride reduction, and periodate cleavage into the erythrose derivative 2a. Oxidation of lactol 2a (95%) using N-iodosuccinimide and tetrabutylammonium iodide' gave the corresponding lactone 2b (87%). &Lactone 4b (42%) was prepared from (1)For example, see: Ozinskas, A. J.; Rosenthal, G. A. J. Org. Chem. 1986,51,5047. Evans, B. E.; Rittle, K. E.; Homnick, C. F.; Springer, J. P.; Hirshfield, J.; Verber, D. F. J. Org. Chen. 1985,50, 4615. Nyberg, 1957,79, 1222. D. D.; Christensen, B. E. J. Am. Chem. SOC. (2) For the direct synthesis of a simple y-[(tert-butyldiphenylsilyl)oxy]
carboxylic acid from the corresponding y-lactone, see: Labadie, J. W.; Tueting, D.; Stille, J. K. J. Org. Chem. 1983,48,4634. (3)Baptista, M. J. V. 0.;Barrett, A. G. M.; Barton, D. H. R.; Girijavallabhan, M.; Jennings, R. C.; Kelly, J.; Papadimitriou, V. J.; Turner, J. V.; Usher, N. A. J. Chem. SOC.,Perkin Trans. 1 1977,1477. (4)Barrett, A. G.M.; Dhanak, D. Tetrahedron Lett. 1987,28,3327. (5)For a discussion of carboxylic acid protection via amides, see: Greene, T. W. Protectiue Groups in Organic Synthesis; J. Wiley and Sons: New York, 1981;pp 187-192. (6)Whistler, R. L.;BeMiller, J. N. In Methods in Carbohydrate Chemistry; Whistler, R. L., Wolfrom, M. L., Eds.; Academic Press: New York, 1963;Vol. 2, p 484. (7)Hanessian, S.; Wong, D. H.; Therien, M. Synthesis 1981, 394.
L-rhamna16via 0-methylation: hydroxymercuration,'O and DMSO-acetic anhydride oxidation.'l The other lactones 6,12 7,138,149,15 10,l6and 111' were all prepared by using established procedures. y-Butyrolactone reacted smoothly with 2-(2-propenyl)anilineand dimethylaluminum chloride
3 a R1=R4=H, R3=0Re
2 a X,Y=H,OH
1
b X,Y,=O
X
R2=Me
b R1=CH201e R2=R3=H, R4=0Me
Ofle
I
ne0
Y
4 a X,Y=H,OH
5 a X,Y=H,OH
b X,Y=O
b X,Y=O
6
8
7
PhCH2
b
;
h
"
O
b
0
H' PhCH20
9
O X 0 10
11
(8) Iselin, V. B.; Reichstein, T. Helu. Chim. Acta 1944,27,1146. (9)Hirst, E. L.;Percival, E.In Methods in Carbohydrate Chemistry; Whistler, R. L., Wolfrom,M. L., Eds.;Academic Press: New York, 1963; Vol. 2,p 145. (10)Brown, H. C.;Geoghegan, P., Jr. J. Am. Chem. SOC. 1967,89, 1522. (11)Sowa, W.; Thomas, G. H. S. Can. J. Chem. 1966,44,836. (12)Nemoto, H.; Nagai, M.; Fukumoto, K.; Kametani, T. J. Org. Chem. 1985,50,2764. (13)Attwood, S. V.; Barrett, A. G. M. J. Chem. SOC., Perkin Trans. 1 1984,1315. (14)Barrett, A. G. M.; Broughton, H. B.; Attwood, S. V.; Gunatilaka, A. A. L.J. Org. Chem. 1986,51,495. (15)Rabinsohn, Y.; Fletcher, H. G., Jr. J. Org. Chem. 1967,32,3452. (16)Hough, L.;Jones, J. K. N.; Mitchell, D. L. Can. J. Chem. 1958, 36, 1720. (17)Morgenlie, S. Carbohydr. Res. 1975,41,77.
0022-3263/89/1954-3321$01.50/00 1989 American Chemical Society
3322 J. Org. Chem., Vol. 54, No. 14, 1989
Barrett et al.
Table I. Conversion of y- a n d &Lactones into Protected yand &Hydroxy Carboxylic Acids
entry 1 2
amide (%) 12a (80)
protected amide (%) 12b (100) 12c (84Ib 13b (86) 13c (78)b 14a (62)b 15b (76) 16b (95) 17b (99) 18a (5l)* 19a (88)b 20b (98) 21a 22a ( 4 2 ) b
a 13a (99)
3
a
4
5
a
I
15a (82) 16a (79)
8
17a (83)
9
a a 20a (79)
6
10 11 12 13
a
a
indole (%) 12d (69) 12e (93) a 13d (61)
14b (57) a a 17c 18b 19b a 21b 22b
(95) (68) (79) (69) (42)
carboxylic acid 12f (68)c 12g 13e 13f 14c 15c 16c 17d 18c 19c 20c 21c 22c
(54)
(67)c (75) (88) (62)c (63)' (58) (81) (87)
in dichloromethane18 solution t o produce the corresponding anilide 12a (80%). T h i s material was protected as t h e 2-[(trimethylsilyl)ethoxy]methyl (SEM)Ig e t h e r 12b (100%). Subsequent ozonolysis of 12b with a dimethyl sulfide workupz0 readily gave t h e N-acylindolezl 12d. We anticipated, on t h e basis of t h e known chemistry of acylindoles,2zt h a t saponification of 12d should be facile. T h u s reaction of 12d with potassium tert-butoxide in wet diethyl ether according t o t h e excellent Gassman procedurez3 gave t h e target carboxylic acid 12f in respectable overall yield from t h e amide 12b (68%).
R
o
d
x
RO
b R=Me3SiCH2CH20CH2, c R='BuPh2Si, X=NHRr d R=ne3SiCH2CH20CHz,
e R='BuPh2Si,
X=NHRr
X=l-indolyl
X-1-indolyl
R = n e 3 S i C H z C H z 0 C H 2 , X=OH g R='BuPh2Si, X=OH
f
Ax
1 3 a R=H, X=NHRr b R='Buile2SI, X=NHAr c R='BuPh2Si,
X=NHPr
d R='BuPhpSi,
X=l-indolyI
e R*'Bunc2Si,
X-OH
f R='BuPh2Si,
X=OH
0 x .
o.
(76) (82)
"Intermediate not isolated. bYield based on starting y- or 6lactone. Yield based on protected amide.
1 2 a R=H, X=NHRr
verted into t h e corresponding protected 2-(2-propenyl)anilides, acylindoles, a n d protected y- or &hydroxy acids (Table I). I n entries 9 a n d 10 t h e acyl indoles 18b a n d 19b were hydrolyzed using lithium hydroxide in aqueous THF at reflux. The use of the Gassman hydrolysis resulted in partial C-2 epimerization in these systems. I n entries 12 and 13 methanolic potassium hydroxide was used in the hydrolysis step. P-Elimination was a major problem on reacting 21b with potassium tert-butoxide in wet diethyl ether.
X OSiPh2'Bu
0
OSiPh2'8u
19 a X=NHAr
18 a X=NHRr b X.1-indolyl c X=OH
b X=1-indolyl c X=OH
S i Ph
ne
cox
Bu
cox
OR 20 a R-H, X-NHRr b R=CH20fle, X=NHRr c R = C H 2 0 N e , X=OH
21 a X = N H R r b X=l-indolyl c X=OH
iPhetBu
ne&
ne0
cox
22 a X=NHRr b X=l-indolyl c
X=OH
\\
Y
In s t r u c t u r e s 1 2 - 2 0 N H R r =
15 a R - H , X = N H R r b R = ' B u M e 2 S i , X=NHRr c R='BuneZSi, x=on
1 4 a X=NHRr b X=indolyl c X=OH
17 a R=H,
16 a R=H, X=NHRr
X=NHRr
b R=neOCH2CH20CHz,
X=NHRr
b R=SIPh2'Bu,
c R=lleOCH2CH20CH2,
X=OH
c R=SiPh2'Bu,
X=NHRr X-1-indolyl
d R=SiPh2'Bu,
X=OH
Using comparable reactions, y-butyrolactone, 6-valerolactone, a n d t h e lactones 2b, 4b, 5b, a n d 6-1 1 were con(18) Basha, A.; Lipton, M.; Weinreb, s. M. Tetrahedron Lett. 1977, 4171. (19) Lipshultz, B. H.; Pegram, J. J. Tetrahedron Lett. 1980,21,3343. (20) Pappas, J. J.; Keaveney, W. P.; Gancher, E.; Berger, M. Tetrahedron Lett. 1966, 4273. (21) For a succinct review of indole synthesis, see: Brown, R. T.; Joule, J. A. In Comprehensiue Organic Chemistry; Barton, D. H. R., Ollis, W. D., Eds.; Pergamon Press: Oxford, 1979; Vol. 4, pp 458-463. (22) For studies on the hydrolysis of n-acylindoles, see ref 21 pp 433-438. Linda, P.; Stener, A.; Cipiciani, A.; Savelli, G. J . Heterocycl. Chem. 1983, 20, 247. (23) Gassman,P. G.; Hodgson, P. K. G.;Balchunis, R. J. J. Am. Chem. SOC.1976, 98, 1275.
It is clear from t h e results in Table I t h a t t h e method is mild, efficient, and general. Both diverse acetal and silyl protecting groups are retained in t h e reaction a n d undesirable relactonization completely suppressed. T h e method is especially useful for t h e synthesis of functionalized aldonic acids needed for redox g l y c o ~ i d a t i o n . ~ ~ Experimental Section General P r o c e d u r e s . All reactions were carried out under dry N2 at room temperature unless otherwise stated. Low reaction temperatures are recorded as bath temperatures. Melting points were determined on a Reichert hot stage apparatus and are uncorrected. Optical rotations were all recorded at room temperature. Microanalyses were determined at Galbraith Laboratories, Knoxville, TN, or by G. D. Searle and Co., Skokie, IL. Column chromatography was carried out on E. Merck silica gel 60,230-400 mesh ASTM, analytical thin-layer chromatography (TLC) was performed on E. Merck precoated silica gel 60 F254 plates. Hexanes refer to the redistilled ACS reagent with boiling range 35-60 "C. The following solvents were purified by distillation: CH2C12(from CaH,, N2),EtPO (from Ph2CO-Na, N2), THF (from Ph,CO-Na, N2),DMF (from CaH2,N,) and 'Pr,NEt (from CaH2, N2). Organic extracts were dried over Na2S04or MgSO,, filtered, and rotary evaporated at 150 "C; involatile oils (24) Barrett, A. G. M.; Bezuidenhoudt, B. C. B.; Gasiecki, A. F.; Howell, A. R.; Russell, M. A. J. Am. Chem. SOC.1989, 111, 1392.
Conversion of Lactones to Protected Hydroxy Acids were further evaporated at
