Photochemistry of 4-(2'-aminoethyl)quinolones: enantioselective synthesis of tetracyclic tetrahydro-1aH-pyrido[4',3':2,3]- cyclobuta[1,2-c] quinoline-2,11(3H,8H)-diones by intra- and intermolecular [2 + 2]-photocycloaddition reactions in solution.
Enantioselective [2 + 2]-photocycloaddition reactions on 4-(2'-aminoethyl)quinolones in solution were studied using the enantiomerically pure complexing agent 1 as source of chirality. The intermolecular reactions of fully N-protected substrates 5a-5c with different 2-alkyl-substituted acrylates 12-15 represent the first systematic study on the diastereoselectivity of their intermolecular [2 + 2]-photocycloadditions to unsymmetrically 1,1-disubstituted olefins (75-91% yield, d.r. = 58/42-95/5). N-Benzylic-protected photoproducts exo-16a/b-19a/b could easily be converted into lactams 20a/b-23a/b by a sequence of Boc deprotection and thermal lactamization (74-98% yield). Identical products 20a-22a were directly accessible by the intramolecular [2 + 2]-photocycloaddition of acrylic acid amides 2-4 (41-61% yield). The suitability of both pathways for an enantioselective reaction variant was proven (70-92% ee). Thus, tetracyclic lactams possessing the carbon framework C were obtained with good yields and enantioselectivities of up to 92% ee in intramolecular reactions. Comparative investigation of both routes showed that quinolone dimerization was the single most decisive factor preventing a complete chirality transfer. Functional group manipulations were successfully conducted with the primary photoproduct exo-17a. Finally, a new and unexpected type of benzylic hydrogen abstraction-radical cyclization reaction was discovered for substrate 5a, which explains the photochemical instability of substrates 2-5 under short wavelength irradiation (lambda = 300 nm).
Selig
Philipp
P
Lehrstuhl für Organische Chemie I, Technische Universität München, D-85747 Garching, Germany.
Bach
Thorsten
T
D000475:Alkenes / Q000737:chemistry; D003500:Cyclization; D003503:Cyclobutanes / Q000737:chemistry*; D007769:Lactams / Q000138:chemical synthesis* / Q000737:chemistry / Q000528:radiation effects; D008968:Molecular Conformation; D015394:Molecular Structure; D010777:Photochemistry; D011725:Pyridines / Q000737:chemistry*; D011804:Quinolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000528:radiation effects; D015363:Quinolones / Q000737:chemistry* / Q000528:radiation effects; D013237:Stereoisomerism; D014466:Ultraviolet Rays
D000475:Alkenes; D003503:Cyclobutanes; D007769:Lactams; D011725:Pyridines; D011804:Quinolines; D015363:Quinolones; C037219:quinoline; C023666:pyridine