J. Org. Chem. 1994,59,67-73
67
Stereoselective Synthesis of 3(2H)-Dihydrofuranonesby Addition of Lithiated Methoxyallene to Chiral Aldehydes Stephan Hormuthf and Hans-Ulrich Reissig'J Znstitut fGr Organische Chemie der Technischen Hochschule Darmstadt, Petersenstrasse 22, 0-64287 Darmstadt, Germany, and Znstitut fGr Organische Chemie und Farbenchemie der Technischen Universitst Dresden, Mommsenstrasse 13,D-01062 Dresden, Germany Received August 17, 19930
Lithiated methoxyallene 2 adds to chiral aldehydes such as 2-phenylpropanal and NJV-dibenzylated a-amino aldehydes 4-8 to give products 9-14 in good yields and with excellent anti-selectivity. The stereochemical outcome of these reactions can be explained by the Felkin-Anh model in a straightforward manner. The crude reaction products can either be transformed to enones by derivatives 19-24 by treatment hydrolysis with acid or be converted into 2,5-dihydro-3-methoxyfuran with potassium tert-butoxide in DMSO. The latter can be hydrolyzedto give 3(2H)-dihydrofuranones 25-29. The diastereoselectivityof the initial addition step is transferred to the dihydrofuranderivative without a major change in the isomer ratio. Compounds derived from a-amino aldehydes 5,6, and 8are assumed to be enantiomericallypure. Sodiumborohydridereductions of and Grignard additions to 3(2H)-dihydrofuranones 27a and 28a demonstrate that these chiral ketones react in a highly diastereoselectivemanner. In summary, this paper shows that lithiated methoxyallene 2 can serve as a very useful equivalent for a,&unsaturated acyl anions and l,&dipolar synthons in asymmetric synthesis. The conversion of a-amino acids into other classes of enantiomerically pure compounds is an important tool for synthetic chemists.' N-Protected a-amino aldehydes2 are extremelysuitable intermediates for this purpose, and many nucleophiles have been added with excellent stereocontroPto provide aminoalcoholsand other compounds of general imp~rtance.~ Lithiated methoxyallene5is a very promisingnucleophile because the products of its addition to aldehydes or to ketones can be converted into a variety of interesting compound classes such as enone@ or dihydrofuran derivative^.^ However, additions of this organometallicspeciesto chiral aldehydeshave rarely been studied? and there has been no systematic investigation t Institut fOr Organische Chemie der Technischen Hochechule Darmstadt. 8 Institut fiir Organische Chemie und Farbenchemie der Technischen Universitllt Dresden. Abstract published in Advance ACS Abstracts, December 1,1993. (1) (a)Reetz, M. T. Angew. Chem. 1991,103,1559. Angew. Chem.Int. Ed. Engl. 1991, 30, 1531. (b) Coppola, G. M.; Schuster, H. F. In Asymmetric Synthesie: Construction of Chiral MOleCUk?S Using Amino Acids; Wiley New York, 1987. (c) Martens, J. Top. Curr. Chem. 1984, 125,165. (d) Williams, R. M. In Synthesis of Optically Actiue a-Amino Acids; Baldwin, J., Magnue, P. D., Eds., Organic Chemistry Series, Pergamon Press: Oxford, 1989; Vol. 7. (2) For review on the preparation and the w e of a-amino and a-alkoxy aldehydes see: (a)Fisher, C. E.; Muchoweki,J. M. Org. Prep. Proced. Int. 1990,22,399. (b) Jurczak, J.; Golebiowski,A. Chem. Reu. 1989,89,149. ( 3 ) (a) Reetz, M. T.; Drewee, M. W.; Schmitz, A. Angew. Chem. 1987, 99,1186. Angew. Chem. Znt.Ed. Engl. 1987,26,1141. (b) Reetz, M. T.; Jaeger, R.; Drewlies, R.; Habel, M. Angew. Chem. 1991,103,76. Angew. Chem. Znt. Ed. Engl. 1991,30, 103. (4) (a) Lednicer, D. A.; Mitscher, L. A. The Organic Chemistry of Drug Synthesis; Wiley: New York, 1975. (b) Nakaniehi, K.; Goto, T.; Natori, S.; Nozoe, S. Natural Products Chemietry; Oxford University Preee: Oxford, 1983, Vol. 3. (c) Kennedy, F. J.; White, A. C. Bioactiue Carbohydrates; Ellis Horwood: Chicheater, 1983. (5) (a) Hoff, S.; Brandama, L.; Arena, J. F. Recl. Trou. Chim. Pays-Boa 1968,87,916. (b) Weiberth, F. J.; Hall, S. S. J. Org. Chem. 1985,60,6308. (c) For a recent review of the chemistry of alkoxyallenes see: Zimmer, R. Synthesis 1993,165. (d) For a detailed discussion of structure and reactivity of 2 based on ab initio calculations and NMR studies see: Schleyer, P. v. R.; Lambert, C.; Wllrthwein, E. U. J. Org. Chem. 1993,68,
6377. (6) Hoff, 5.;Brandama, L.; Arens, J. F. Recl. Trau. Chim. Pays-Ea8 1968.87.1179.
(7) Hoff, S.; Brandsma, L.; Arena, J. F. Recl. Trau. Chim. Pays-Bos
1969,88,609.
-7ST
"MPh 0
Me
+*
h*
Me
HO
HO
Me
9b
90
(86 : 14)
diastereomers to 81:19 (84% yield). The antksyn ratio of 86:14 demonstrates that lithiated methoxyallenedisplays reasonable diastereofacial selectivity comparable to that of other (a,&unsaturated) acyl anion equivalents.1o Lithi(8) (a) Goldstein, S. W.; Overman, L. E.; Rabinowitz, M. H. J. Org. Chem. 1992, 67, 1179. (b) Shiehido, K.; Takaha~hi,K.;W o , Y.; Fukumoto, K. Heterocycles 1989,27,495. (c) Gange, D.; Magnw, P. J. Am. Chem. Soc. 1978, 100, 7746. (d) For further applicationr, of alkoxyalleneein asymmetric synthesis see: W e t , P. R.; VatAle, J.-M.; God, J. Synlett 1993,105. Amold,T.; Oreche1,B.; Reieaig,H.-U. Angew. Chem. 1992,104,1084. Angew. Chem. Int. Ed. Engl. 1992,31,1033. (9) For a preliminary communication see: Hormuth, S.; Reiiig, H.-U. Synlett 1991, 179.
0022-326319411959-0067$04.50/0 0 1994 American Chemical Society
Hormuth and Reissig
68 J. Org. Chem., Vol. 59, No. 1, 1994
Scheme 2
Scheme 1 H
NBn2
HO
HO Aldehyde
Adducts
e lanti) R = H
Yield b lsynl
B
4
10
Me
6
lldllb
CHZPh
8
12d12b
= 8 9 : 11
quant.
13d13b
= 86 : 14
90%
14d14b
= 8 0 : 20
77%
C H ~ O S I Z B U M ~7 ~
CH2iPr
lldllb
8
90% = 95: 5
94%
imidazole
110
[gives syn)
1I d 192 : 81
ated methoxyallene (2) also added smoothly to readily availableNJV-dibenzyl-protecteda-amino aldehydes4-8% (Scheme 1). Adducts 10-14 were formed in excellentcrude yields, but they could not be purified by distillation or chromatography without extensive decomposition. There fore, the diastereomer ratios were determined by NMR spectroscopy at the crude stage, and the full characterization and purification were carried out on subsequent products (videinfra). Alanine-derivedadducts1 la/b were also converted into the dimethyl-tert-butylsilylatedll compounds, which are stable to chromatography. The configuration of major diastereomer l l a was deduced unambiguously by X-ray analysis of cyclization product 27a,13and, hence, for all additions of 2 to aldehydes 3-8, the formation of anti-configurated compounds can be assumed. These results are rationalized by applying the Felkin-Anh model." According to Reetz, N-dibenzylated a-amino aldehydes are attacked by organolithium compounds without chelate formation.'* Thus, conformerA,with the dibenzylaminogroup in the position of the largest substituent, governs the additions of 2 and, hence, leads to anti-adducts (Scheme 2). The trend that larger groups R on the amino aldehydes lead to slightly decreased diastereoselectivity is also in accordance with this explanationsince,as the sizeof R increases,conformer B competes with conformer A, which is still preferred, and the formation of alarger amount of minor diastereomer b is observed. In order to reverse the diastereoselectivity of the additions of 2, we used N-Boc-protectedamino aldehydes's (10) (a)H W , S . ;Marachner,C. Chem.Ber. 1989,122,1329. (b)H e , S.; Marechner,C.; Peters, K.;v. Schnering, H.-G. Chem. Ber. 1989,122, 2131 and refs cited therein. (c) Barett, A. G. M.; Lebolg, S. A. J. Org. Chem. 1990,66,6818. (d) Braun, M.; Mahler, H. Synlett 1990,587 and refs cited therein. (e) See a l m Senjupta, S.;Snieckus, V. J. Org. Chem. 1990,56,5680 and refs cited therein. (0For a comprehensive lint of acyl anions nee: Umpolung ~ y n t h o Haw, ~ ; T.A., Ed.;Wiley: New York, 1987. (11) Corey, E. J.; Venkatewarlu, A. J. Am. Chem. SOC. 1972,94,6190. (12) Amino aldehyde 7 was employed as ita racemate, consequently, compounds 18 and 28, derived from 7, were also racemates. (13) Hormuth,S.;~~,H.-U.;Foro,S.;Lindner,H.J.Z.K~tallogr. 19911, in p m . (14) (a) Chbreet, M.; Felkin, H.; Prudent, N. Tetrahedron Lett. 1968, 2199. (b) Anh, N. T. Top. Curr. Chem. 1980, 88, 145. (c) See &o: Frenking, G.; K(lhler, K.F.; Reeta, M. T.Tetrahedron 1998,49, 3971.
as electrophiles. However, the expected products were formed in very low yields (
