J. Org. Chem. 1994,59, 7930-7933
7930
Stereoselective Synthesis of /3-Oxygenated a-Hydroxyphosphonatesby Lewis Acid-Mediated Stereoselective Hydrophosphonylation of a-Benzyloxy Aldehydes. An Application to the Synthesis of Phosphonic Acid Analogs of Oxyamino Acids Tsutomu Yokomatsu, Yoshinori Yoshida, and Shiroshi Shibuya" Tokyo College of Pharmacy, 1432-1Horinouchi, Hachioji, Tokyo 192-03,Japan Received J u n e 13, 1994
The synthesis of chiral a-substituted phosphonic acids has been an important area of research, particularly in connection with the search for the biologically active surrogates for the corresponding carboxylic acids and phosphoric acid esters.l a-Hydroxyphosphonic acid derivatives are gaining in interest in medicinal chemistry, since they are potentially useful inhibitor of enzymes such as protease,2 EPSP ~ y n t h a s eand , ~ thyrosin-specific protein k i n a ~ e In . ~ contrast to extensive studies for the stereoselective synthesis of a-aminophosphonic acid,6 stereocontrolled syntheses of a-hydroxyphosphonic acid derivatives have only recently begun to receive attention.6 Our interest in this area centers on the development of versatile phosphonic chirons for the synthesis of various a-substituted phosphonic acid derivatives which would be of biological interest. The chiral glycol phosphonate such as 1 would constitute one of the most useful phosphonic chirons for this purpose if both hydroxy groups could subsequently be transformed selectively (Scheme 1). In this paper we disclose Lewis acidmediated stereoselective hydrophosphonylations of a-benzyloxy aldehydes for the synthesis of a,P-dioxygenated phosphonates and their selective conversion to P-oxygenated a-aminophosphonic acids,7phosphonic acid analogs of oxyamino carboxylic acids. We first investigated the stereoselective synthesis of P-(benzyloxy)-a-hydroxyphosphonates 8 , a mono-protected form of glycol 1 (Scheme 2, Table 1). The Lewis acid-mediated hydrophosphonylation of a-benzyloxy al~
~
~~
(1)The Role of Phosphonates in Living Systems; Hilderbrand, R. L. Ed.; CRC Press, Boca Raton: FL, 1983;Handbook of Organophosphorus Chemistry; Engel, R. Ed.; Marcel Dekker, Inc.: New York, 1992. (2)Patel, D. V.; Rielly-Gauvin, K.; Ryono, D. E. Tetrahedron Lett. 1990,31,5587. Idem. Ibid. 1990,31,5591. Stowasser, B.; Budt, K-H.; Jian-Qi, L.; Peyman, A.; Ruppert, D. Ibid. 1992,33,6625. (3)Shikorski, J. A.;Miller, M. J.; Baccolino, D. S.; Cleary, D. G.; Corey. D. G.; Font, J. L.; Gruys, K J.; Han, C. Y.; Lin, K. C.; Pansegrau, P. D.; Ream, J. E.; Schnur, D.; Shan, A; Walker, M. C. Phosphorus Sulfur Silicon 1993,76, 115. (4)Bruke, T. R., Jr.; Li, Z-H.; Bolen, J. B.; Marquez, V. E. J. Med. Chem. 1991,34,1577. (5) Denmark, S.E.; Chatani, N.; Pansare, S. V. Tetrahedron 1992, 48,2129 and references cited therein. (6)(a) Yokomatsu, T.; Shibuya, S. Tetrahedron Asymmetry 1992,3, 377.(b) Anita, V. S.; Davies, A. J.; Kee, T. P. J. Chem. Soc., Chem. Commun. 1992,1771.(c) Yokomatsu, T.; Yamagishi, T.; Shibuya, S. Tetrahedron Asymmetry 1993,4, 1779. (d) Idem. Ibid. 1993,4 , 1783. (e) Liu, Y-F.; Hammerschmidt, F. Tetrahedron Lett. 1993,34,109.(0 Kishi, T.; O'Toole, K. J.; Sime,T. Ibid. 1993,34,2375.( g ) Gordon, N. (h) Sum, V.; Kee, J.; Evans, S. A. J. Org. Chem. 1993,58,5293,5295. T. P. J.Chem. Soc., Perkin Trans. 1 1993,2701.(i) Rath, N. P.; Spilling, C. D. Tetrahedron Lett. 1994,35,227. (7)Hammerschmidt, F.; Vollenkle, H. Liebigs Ann. Chem. 1989,577.
Scheme 1
HO
I
0
0
HO
a-selective functionalization
X
1
functionalization
OH
Scheme 2 En0 R' ACHO
+
t-BuMe2SiOP(OR2)2
2: R1=CH2Ph 3: R1=CHMe2 4: R 1=Me
5: R2-Me 6: R2=Et 7: R2=i-Pr
TiCll / CHpC12/ -78 O Cc
En?
9
R, Py.P(OR2), X s y n - 8 X- ---OH anfi-8 X- -OH
r
L
1
A
dehydes 2-48 with silyl phosphites 5-79 was examined as an extension of our recent investigation on the hydrophosphonylation of a-dibenzylamino aldehydes.1° Table 1summarizes the stereoisomer distributions thus obtained by the use of Tic14 as the Lewis acid. All reactions proceeded with stereoregular diastereo-preference for giving syn-8 via chelate complex A.l1-I3 Of special interest is that the syn-selectivity observed with 2-4 depends on the steric bulkiness of the alkyl group (R2) in the silyl phosphite 5-7;14 the syn-selectivity increases from 75 to 84% on going from R2 = i-Pr to R2 (8)The aldehydes 2 and 3 were prepared in enantiomerically pure forms from the corresponding L-amino acids according to literature methods and used without purification: Mead, K. T. Tetrahedron Lett. 1987,28,1019.Ireland, R. E.; Thaisrivongs, S.;Dussault, P. H. J.Am. Chem. Soc. 1988,110,5768. (9)Evans, D. A.;Hurst, K M.; Takacs, J. M. J. Am. Chem. Soc. 1978,100,3467. (10)Yokomatsu, T.; Yamagishi, T.; Shibuya, S. Tetrahedron Asymmetry 1993,4,1401. (11)Reetz, M. T. Organotitanium Reagents in Organic Synthesis, Springer-Verlag, Berlin Heidelberg, 1986. (12) The reaction of an aldehyde 4 with silyl phosphite 6 in the absence of T i c 4 in CHzClz at room temperature proceeded very slowly to give the silyoxy adduct i with anti-stereochemistry (36% de). The similar results were reported by Hammerschmidt: Hammerschmidt, F. Liebig Ann. Chem. 1991,469.
(13)During the formation of the phosphorus to carbon bond in these reactions, no racemization of 2 and 3 takes place; optical purities ('98% eel of 8a,b were confirmed by NMR analysis of the corresponding Mosher esters derived from (+I- and (-)-a-methoxy-a-(trifluoromethy1)phenylacetic acids. (14)The effects of bulkiness of the ester alkyl group on the stereochemical outcome are not clearly explained a t present.
0022-3263/94/1959-7930$04.50/00 1994 American Chemical Society
J. Org. Chem., Vol. 59, No. 25, 1994 7931
Notes
Table 1. Lewis Acid-Mediated StereoselectiveHydrophosphonylation of a-BenzyloxyAldehydes with Silyl Phosphites 5-7 entry
aldehyde
phosphite"
product
yield (%)
ratio (syn/unti)b
>98:
