Angewandte
Chemie
Scheme 4. Synthesis of SPT inhibitors, viridiofungin A and NA 808. Reaction conditions: a) AgPF6/(S)-4/DBU=1:1:1 (3 mol%), toluene, À208C,
24 h, 71%, syn/anti=13:1, 98% ee (syn); b) LiAlH4 (6 equiv), THF, reflux, 1 h, 82%; c) TBDPSCl (2.2 equiv), Imidazole (6.0 equiv), DMF, RT, 2 h,
81%; d) MeOTf (1.2 equiv), NaHCO3 (2 equiv), diethyl ether, RT, 16 h; e) DBU (4 equiv), diethyl ether, RT, 1 h, 95% (2 steps); f) DDQ (2.0 equiv),
CH2Cl2/H2O (20:1), RT, 1.5 h, 95%; g) 12 (5.2 equiv), Cp2Zr(H)Cl (5.5 equiv), MeMgBr (10.3 equiv), CuI (0.4 equiv), THF, À258C, 36 h, 75%;
h) PPTS (1 mol%), CH2Cl2/2,2-DMP (5:4), RT, 37 h, 74%; i) TBAF (2.2 equiv), AcOH (2.0 equiv), THF, RT, 50 h, 85%; j) (COCl)2 (8 equiv), DMSO
(16 equiv), Et3N (26 equiv), CH2Cl2, À788C, 1 h; k) NaClO2 (10 equiv), NaH2PO4 (7.5 equiv), 2-methylbut-2-ene (70 equiv), tBuOH/H2O (3:1),
08C, 4 h; l) N,N’-diisopropyl-O-tert-butylisourea (10 equiv), CH2Cl2, RT, 48 h, 53% (3 steps); m) AcOH/H2O/THF (4:1:5), RT, 3 h, 91%; n) CrO3
(2.5 equiv), acetone, À78 to 08C, 1 h; o) for 8 (R=H): 16 (3 equiv), HATU (3 equiv), iPr2NEt (3 equiv), DMF, RT, 14 h, 45% (2 steps), for 9
(R=CH2CCH3): 17 (HCl salt) (2 equiv), HATU (2 equiv), iPr2NEt (4 equiv), DMF, RT, 10.5 h, 20% (2 steps); p) for 8: HCO2H, RT, 1 h,
quantitative; q) for 9: anisole (9 equiv), TFA, 08C to RT, 16 h, quantitative. Cp=cyclopentadienyl, DDQ=2,3-dichloro-5,6-dicyano-p-benzoquinone,
2,2-DMP=2,2-dimethoxypropane, DMSO=dimethylsulfoxide, HATU=(7-azabenzotriazol-1-yl)tetramethyluronium hexafluorophosphate,
PPTS=pyridinium p-toluenesulfonate, quant.=quantitative yield, TBAF=tetrabutylammonium fluoride, TBDPS=tert-butyldiphenylsilyl, TFA=tri-
fluoroacetic acid.
acetonide and the TBDPS groups were removed to give diol
13. Oxidation of the primary alcohols to the carboxylic acids
and then esterification to the tert-butyl esters gave 14.
Hydrolysis of both the acetonide and the ketal under acidic
conditions followed by Jones oxidation gave carboxylic acid
15. Amide coupling reaction between l-tyrosine derivatives
16 and 17 and carboxylic acid 15 proceeded smoothly using
HATU and subsequent hydrolysis of the tert-butyl esters
using HCO2H or TFA/anisole furnished 8 and 9, respectively.
In summary, we have developed a direct catalytic
asymmetric aldol reaction between a-sulfanyl lactones 1 and
aldehydes that is promoted by a chiral Ag/DBU binary
catalyst. Chemoselective activation of a-sulfanyl lactones 1 in
the presence of aldehyde, made possible through specific
coordination of the sulfur atom to the Ag cation, resulted in
the preferential enolization of 1 and gave the desired aldol
products 3 with high stereoselectivity. The efficient and
stereospecific displacement of the sulfide functionality of the
product 3ae facilitated a rapid access to a densely function-
alized tertiary alcohol in optically active form, which was
subsequently used as an intermediate in an enantioselective
synthesis of viridiofungin A (8) and NA 808 (9).
580; b) Modern Aldol Reactions (Ed.: R. Mahrwald), Wiley-
VCH, Berlin, 2004; c) S. Mukherjee, J. W. Yang, S. Hoffmann, B.
[2] For a selection of early examples of direct catalytic asymmetric
aldol reactions, see: a) Y. M. A. Yamada, N. Yoshikawa, H.
[3] For direct catalytic asymmetric aldol (-type) reactions using
aldol donors at the carboxylic acid oxidation state without
electron-withdrawing a substituents, see: for alkylnitriles, see:
3757; for the use of activated amides, see: b) S. Saito, S.
unsaturated esters, see: c) A. Yamaguchi, S. Matsunaga, M.
see: d) M. Iwata, R. Yazaki, Y. Suzuki, N. Kumagai, M.
Yazaki, I.-H. Chen, D. Sureshkumar, N. Kumagai, M. Shibasaki,
132, 6286; for an example of a direct catalytic asymmetric aldol
reaction of thiazolidinethiones where the use of a stoichiometric
amount of silylating reagent was essential, see: g) D. A. Evans,
[4] There are numerous examples of direct aldol reactions using
aldol donors bearing electron-withdrawing a substituents that
readily undergo enolization under mild basic conditions. For
pioneering work in this area that uses a-isocyanoacetates, see: Y.
Received: January 18, 2012
Published online: March 13, 2012
Keywords: aldol reaction · asymmetric catalysis · silver ·
.
SPT inhibitor · sulfanyl lactone
[1] For reviews of direct catalytic asymmetric aldol reactions, see:
Angew. Chem. Int. Ed. 2012, 51, 4218 –4222
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
4221