Synthetic studies on the lithiated toluamide-imine cycloaddition route to (.+-.)-corydalic acid methyl ester

A study on the metalation of fluorinated phenyl benzyl ethers

“…1 Snieckus synthesized ochratoxine (a metabolite of Aspergillus ochraceus and Penicillium viridicatum) from 4-chlorophenol using a series of directed ortho lithiations. 2 The other examples involve the ortho lithiation of 1,2-methylenedioxybenzoic acid to obtain corydalic acid methyl ester, 3 ortho lithiation of 2-chloropyridine in the synthesis of the antibiotic atpenin B, 4 benzylic metalation of p-xylene in the synthesis of ibuprofen 5 and (−)-sparteine assisted enantioselective lithiation of carbamate derivative of n-dodecanol. 6 In all mentioned examples the key step relies upon ortho or benzylic lithiation (Fig.…”

Atroposelectivity in the electrophilic substitution reactions of laterally lithiated and silylated tertiary amides

“…The aqueous phase was extracted with dichloromethane (3 × 20 ml), the combined organic extracts were washed with water (30 ml), dried over magnesium sulfate, filtered and the solvent was evaporated. Purification by flash chromatography 58 [3% ethyl acetate in light petroleum] gave the silane 33 (101 mg, 72%) as a colourless oil; R f [5% EtOAc-petrol] 0.32; ν max (film)/cm Ϫ1 1631; δ H (300 MHz; CDCl 3 ) 6.84 (1H, s, Ar), 6.79 (1H, s, Ar), 3.71 (1H, sept, J = 6.7, NCH), 3.51 (1H, sept, J = 6.7, NCH), 2.74-2.43 (4H, m, o-CH A H B CH 3 and p-CH 2 CH 3 ), 2.15 (1H, q, J = 7.4, ArCHCH 3 ), 1.63 (3H, d, J = 6.7, NCHCH 3 ), 1.60 (3H, d, J = 6.7, NCHCH 3 ), 1.36 (3H, d, J = 7.4, ArCHCH 3 ), 1.26 (6H, t, J = 7.6, 2 × ArCH 2 CH 3 ), 1.14 (3H, d, J = 6.6, NCHCH 3 ), 1.08 (3H, d, J = 6.6, NCHCH 3 ), 0.00 (9H, s, Si(CH 3 ) 3 ); δ C (75 MHz; CDCl 3 ) 170.2 (s, CO), 143.1 (s, Ar), 142.1 (s, Ar), 139.4 (s, Ar), 133.5 (s, Ar), 123.6 (d, Ar), 122.8 (d, Ar), 49.9 (d, NCH), 45.5 (d, NCH), 28.8 (t, ArCH 2 ), 25.8 (d, ArCH), 25.1 (t, ArCH 2 ), 20.9 (q, 2 × NCHC H 3 ), 20.3 (q, NCHC H 3 ), 20.2 (q, NCHC H 3 ), 16.3 (q, ArCHC H 3 ), 15.4 (q, CH 2 C H 3 ), 15.1 (q, CH 2 C H 3 ), 2.6 (q, Si(CH 3 ) 3 ); m/z (CI) 364 (19%), 362 (100), 361 (18), 332 (19), 189 (33), 90 (17), 73 (65) (Found: M ϩ , 361.2796. C 22 H 39 NOSi requires M, 361.2801).…”

“…16 For example, lateral lithiation of amide 1 gives organolithium 2 which generates only a single diastereoisomer of the amine 3 (an intermediate in a synthesis of corydalic acid methyl ester) on addition to an imine (Scheme 1). 17 Similar reactions lead to enantiomerically enriched products in the presence of sparteine. 18 Also in the enantiomerically pure series, lateral lithiation of 4 gives organolithium 5 which is configurationally labile at the lithium-bearing centre but which reacts enantioselectively in the presence of (Ϫ)-sparteine and produces laterally functionalised products 6 in up to 92% ee (Scheme 2).…”

“…The anti relative stereochemistry of the stereogenic centres of 22a is in keeping with precedent (see, for example, Scheme 1). 17 By analogy (see also compound 45a below), we therefore assign the stereochemistry shown to the other imine 23a and the other stannanes 25. The stereochemistry of the silylated compound 18a was assigned by its stereospecific Fleming-Tamao oxidation 37, 38 to the known 31 alcohol 31 (Scheme 7); by analogy we assign the stereochemistry shown to the pair of silylated diastereoisomers 17.…”

1H NMR and X-ray conformational analyses of (+)-corydalic acid methyl ester, a 6,7-secoberbine alkaloid

“…The geometry of 1 was shown to be methyl (6R-trans)-6-(6,7,8,9tetrahydro-6,8-dimethyl-1,3-dioxolo[4,5-h]isoquinolin-7-yl)-1,3-benzodioxole-5-acetate, which is consistent with that elucidated by chemical correlation and synthetic methods. 1,4- 10 The absolute configuration at C(13) and C(14) of 1 is set to the same configuration revealed 12 from a derivative from 1. The ring B of 1 adopts a half-chair conformation as shown in Fig.…”