A methodology involving a "transition metal-free" intramolecular biaryl-coupling of o-halo-N-arylbenzylamines has been developed in the presence of potassium tert-butoxide and an organic molecule as catalyst. The reaction appears to proceed through KO(t)Bu-promoted intramolecular homolytic aromatic substitution (HAS). Interestingly, this biaryl coupling also works in the presence of potassium tert-butoxide as sole promoter. On extending our approach further, we found that N-acyl 2-bromo-N-arylbenzylamines undergo a one-pot N-deprotection/biaryl coupling followed by oxidation, thus offering an expeditious route to the phenanthridine and benzo[c]phenanthridine skeletons. The strategy has been applied to a concise synthesis of Amaryllidaceae alkaloids viz. oxoassoanine (1b), anhydrolycorinone (1d), 5,6-dihydrobicolorine (2d), trispheridine (2b), and benzo[c]phenanthridines alkaloids dihydronitidine (3b), dihydrochelerythidine (3d), dihydroavicine (3f), nornitidine (3h), and norchelerythrine (3j).
Echitamine (1)a nd akuammiline (2)a re representative members of afascinating class of monoterpenoid indole alkaloids.W er eport the syntheses of 2 and its congener deacetylakuammiline (3). The azabicyclo[3.3.1]nonane motif was assembled through silver-catalyzed internal alkyne cyclization, and one-pot C À Obond cleavage/C À Nbond formation furnished the pentacyclic scaffold. Compound 3 then served as ac ommon intermediate for preparing as eries of structurally diverse and synthetically challenging congeners including 1.A position-selective Polonovski-Potier reaction followed by formal N-4 migration built the core of N-demethylechitamine (4)a nd 1.A na lternative route featuring Meisenheimer rearrangement gave 4 as well. Oxidation of the alcohol within 3 gave rhazimal (5), whichu nderwent tandem indolenine hydrolysis,h emiaminalization, and hemiketalization to form rhazicine (6). As equence of N,O-ketalization and reductive amination secured the chemoselectivity of N-methylation, leading to pseudoakuammigine (7).
An intramolecular-dehydrogenative-coupling (IDC) using "transition-metal-free" oxidation conditions has been achieved to synthesize a variety of 2-oxindoles bearing an all-carbon quaternary stereogenic center at the benzylic position. The methodology involves a one-pot C-alkylation of β-N-arylamido esters (3, 6) with alkyl halides using potassium tert-butoxide concomitant with a dehydrogenative coupling. A radical-mediated pathway has been tentatively proposed for the oxidative process.
We report a catalytic stereoconvergent construction of vicinal all-carbon quaternary centers via double stereoablative enantioselective alkylation of a mixture having racemic and meso diastereomers of esters to afford exceptional levels of diastereo- (up to 17 : 1) and enantioselectivity (up to >99% ee). The strategy offers an efficient and general approach to dimeric cyclotryptamine alkaloids sharing a labile C(3a)-C(3a') σ-bond in the hexahydropyrroloindoline core.
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