Tandem Enyne Metathesis-Diels−Alder Reaction for Construction of Natural Product Frameworks (original) (raw)
ChemInform, 2008
To a -10 °C suspension of Me 3 SI (3 mmol, 612 mg) in THF (3 ml) was added n-BuLi (3 mmol, 1.9 mL of 1.6 M hexane solution). After 15 min, diendioate 1 (1.0 mmol) in THF (3 mL) was introduced and the reaction mixture was slowly allowed to warm to room temperature. After 1 h, the reaction mixture was cooled on ice-water bath and methyl iodide (0.32 mL, 5 mmol) or allyl bromide/ benzyl bromide (3 mmol) was added and stirred at ambient temperature for 15 h. The reaction mixture was diluted with water and extracted with diethyl ether. The combined extracts were washed with brine, dried over magnesium sulfate, filtered and concentrated under vacuum.
Russ. J. Org. Chem. 2010, 46, 1192-1206 (Zhurnal Organicheskoi Khimii, 2010, 46, 1191-1204)
Partly hydrogenated 2-[5-methyl(bromo, nitro)furan-2-yl]-substituted furo [3,2-c]quinolines, pyrano-[3,2-c]quinolines, and 4-ethoxyquinolines were synthesized by the imino Diels-Alder (Povarov) reaction. Cycloadditions of these compounds with maleic, citraconic, and dibromomaleic anhydrides, as well as with acryloyl, methacryloyl, and cinnamoyl chlorides led to the formation of substituted epoxyisoindolo[2,1-a]quinolines and -quinolinecarboxylic acids. Oxidation of the double C=C bond in the adducts, esterification of the carboxy group, and aromatization of the 7-oxabicycloheptene fragment were accomplished. s (3H, COMe), 2.97 d.d.q (1H, 3a-H, J 3a, 4 = 3.2, J 3a, 9b = 7.6, J 3a, 3 = 8.2 Hz), 3.74 d.t -H, 2 J = 3 J = 8.6 Hz), 3.82 q (1H, 2-H, 2 J = 8.4, 3 J = 4.4 Hz), 4.44 br.s (NH), 4.81 d (1H, 4-H, J 3a, 4 = 3.2 Hz), 5.22 d (1H, 9b-H, J 3a, 9b = 7.6 Hz), 6.30 d.d (1H, 3′-H, 4 J = 0.8, 3 J = 3.2 Hz), 6.38 d.d (1H, 4′-H, J 5′, 4′ = 1.8, J 4′, 3′ = 3.2 Hz), 6.59 d (1H, 6-H, J 6, 7 = 8.5 Hz), 7.40 d.d (1H, 5′-H, J 5′, 4′ = 1.8, J 5′, 3′ = 0.8 Hz), 7.74 d.d (1H, 7-H, J 7, 9 = 2.0, J 6, 7 = 8.5 Hz), 7.97 d (1H, 9-H, J 7, 9 = 2.0 Hz). Mass spectrum, m/z (I rel , %): 283 (100) [M] + , 268 (22), 254 (13), 238 (90), 210 (9), 198 (6), 172 (15), 167 (5), 103 (5), 81 (6), 43 (7). Found, %: C 72.31; H 6.21; N 4.78. C 17 H 17 NO 3 . Calculated, %: C 72.07; H 6.05; N 4.94. M 283.12. 1-H), 2.05 m (1H, 1-H), 2.34 d.d.d (1H, exo-10-H, J 9a, exo-10 = 3.9, J exo-10, 11 = 4.8, 2 J = 12.1 Hz), 2.76 d.d (1H, 9a-H, J 9a, exo-10 = 3.9, J 9a, endo-10 = 9.2 Hz), 3.21 m (1H, 13c-H), 3.89-4.03 m (2H, 2-H), 4.47 d (1H, 13b-H, J 13b, 13c = 3.4 Hz), 5.17 d.d (1H, 11-H, J exo-10, 11 = 4.8, J 11, 12 = 1.5 Hz), 5.37 d (1H, 3a-H, J 3a, 13c = 8.2 Hz), 6.47 d.d (1H, 12-H, J 11, 12 = 1.5, J 12, 13 = 5.8 Hz), 6.57 d (1H, 13-H, J 12, 13 = 5.8 Hz), 6.98 d.d (1H, 6-H, J 5, 6 = 7.7, J 4, 6 = 1.5 Hz), 7.21 t (1H, 5-H, J 4, 5 = J 5, 6 = 7.7 Hz), 7.22 d.d (1H, 4-H, J 4, 5 = 7.7, J 4, 6 = 1.5 Hz), 9.45 s (OH); cis isomer: 1.77 d.d (1H, endo-10-H, J 9a, endo-10 = 9.2, 2 J = 11.6 Hz), 1.90 m (1H, 1-H), 2.13 m (1H, 1-H), 2.17 d.d.d (1H, exo-10-H, J 9a, exo-10 = 3.9, J exo-10, 11 = 4.4, 2 J = 11.6 Hz), 2.55 d.d (1H, 9a-H, J 9a, exo-10 = 3.9, J 9a, endo-10 = 9.2 Hz), 3.15 m (1H, 13c-H), 3.89-4.03 m (2H, 2-H), 4.52 d (1H, 13b-H, J 13b, 13c = 2.9 Hz), 5.14 d.d (1H, 11-H, J exo-10, 11 = 4.4, J 11, 12 = 1.5 Hz), 5.35 d (1H, 3a-H, J 3a,13c = 8.2 Hz), 6.53 d.d (1H, 12-H, J 11, 12 = 1.5, J 12, 13 = 5.8 Hz), 6.58 d (1H, 13-H, J 12, 13 = 5.8 Hz), 7.00 d.d (1H, 6-H, J 5, 6 = 7.7, J 4, 6 = 1.5 Hz), 7.29 t (1H, 5-H, J 4, 5 = J 5, 6 = 7.7 Hz), 7.36 d.d (1H, 4-H, J 4, 5 = 7.7, J 4, 6 = 1.5 Hz), 9.45 s (OH). Mass spectrum, m/z (I rel , %): 311 (31) [M] + , ,13b,13c-hexahydro-3aH-furo[3,2-c]isoindolo[2,1-a]quinolin-9(9aH)-one (VIIId) (mixture of trans and cis isomers at a ratio of 1 : 1. Yield 87%, mp 157-158°C (from hexane-ethyl acetate), R f 0.62, 0.91 (hexane-ethyl acetate, 1 : 1). IR spectrum: ν 1691 cm -1 (C=O). 1 H NMR spectrum (CDCl 3 ), δ, ppm: trans isomer: 1.69 s (3H, Me), 1.80 d.d (1H, endo-10-H, J 9a, endo-10 = 9.0, 2 J = 11.8 Hz), 1.86 m (1H, 1-H), 2.07 d.d (1H, exo-10-H, J 9a, exo-10 = 3.5, 2 J = 11.8 Hz), 2.65 m (1H, 1-H), 2.89 m (1H, 13c-H), 3.72 d.d (1H, 9a-H, J 9a, exo-10 = 3.5, J 9a, endo-10 = 9.0 Hz), 3.86-3.95 m (2H, 2-H), 4.42 d (1H, 13b-H, J 13b, 13c = 2.7 Hz), 5.36 d (1H, 3a-H, J 3a,13c = 8.2 Hz), 6.33 d ( 1H, J 12, 13 = 5.7 Hz), 6.54 d (1H, J 12, 13 = 5.7 Hz), 7.17 d.t (1H, J 4, 5 = J 5, 6 = 7.7, J 5, 7 = 1.1 Hz), 7.32 d.d (1H, J 5, 6 = 7.7, J 6, 7 = 8.1 Hz), 7.42 br.d (1H, J 4, 5 = 7.7 Hz), 8.03 d.d (1H, J 5, = 1.1, J 6, 7 = 8.1 Hz); cis isomer: 1.64 s (3H, Me), 1.71 d.d (1H, endo-10-H, J 9a, endo-10 = 8.7, 2 J = 11.8 Hz), 1.86 m (1H, 1-H), 1.99 d.d (1H, exo-10-H, J 9a, exo-10 = 3.6, 2 J = 11.8 Hz), 2.70 m (1H, 1-H), 3.11 m (1H, 13c-H), 3.66 d.d (1H, 9a-H, J 9a, exo-10 = 3.6, J 9a, endo-10 = 8.7 Hz), 3.84 m (2H, 2-H), 4.70 d (1H, 13b-H, J 13b, 13c = 2.5 Hz), 5.24 d (1H, 3a-H, J 3a, 13c = 7.2 Hz), 6.30 d (1H, 13-H, J 12, 13 = 5.7 Hz), 6.44 d (1H, 12-H, J 12, 13 = 5.7 Hz), 7.11 d.t (1H, 5-H, J 4, 5 = J 5, 6 = 7.7, J 5, 7 = 1.1 Hz), 7.24 d.d (1H, 6-H, J 5, 6 = 7.7, J 6, 7 = 8.4 Hz), 7.48 br.d (1H, 4-H, J 4, 5 = 7.7 Hz), 8.66 d.d (1H, 7-H, J 5, 7 = 1.1, J 6, 7 = 8.4 Hz). Mass spectrum, m/z (I rel , %): 309 (18) [M] + ,
Ethylaluminum dichloride catalyzed ene reactions of aldehydes with nonnucleophilic alkenes
The Journal of Organic Chemistry, 1983
sufficiently reliable to provide an additional method that should be used increasingly in conjunction with existing general procedures to assign the configuration of compounds similar to those described here. Experimental Section The compounds used in this study were prepared by literature methods. Optically active samples of the alcohols were prepared by resolution (3), reduction of the corresponding ketone using Cryptococcus macerans, or by enantioselective hydrolysis of the corresponding acetates using Rhizopus nigricam. The 'H NMR spectra (220 MHz) of the optically active samples were identical with authentic racemic materials. Specific rotations were determined by using a Perkin-Elmer 241MC polarimeter. The HPLC measurements were made by using an apparatus constructed from an Altex injector, an Altex pump Model llOA, a Gilson variable-wavelength detector, and a chiral 'Pirkle" column (Hi-Chrom reversible column) purchased from the Regis Chemical Co., Morton Grove, IL 60053. The column is (R)-N-(3,5-di-nitrobenzoy1)phenylglycine ionically bonded to a y-aminopropyl-silanized silica The alcohols were converted to the corresponding acetates by acetic anhydride/pyridine by using standard techniques. Registry No. la (X = H; isomer l), 1517-69-7; la (X = H; isomer 2), 1445-91-6; la (X = Ac; isomer l), 16197-92-5; la (X = Ac; isomer 2), 16197-93-6; lb (X = H; isomer l), 1565-74-8; lb (X = H; isomer 2), 613-87-6; lb (X = Ac; isomer l), 84275-44-5; lb (X = Ac; isomer 2), 83860-48-4; IC (X = H; isomer l), 22144-60-1; IC (X = H; isomer 2), 22135-49-5; lo (X = Ac; isomer I), 84194-64-9; IC (X = Ac; isomer 2), 84194-65-0; Id (X = H; isomer l), 14898-86-3; Id (X = H; isomer 2), 34857-28-8; Id (X = Ac; isomer l), 84194-66-1; Id (X = Ac; isomer 2), 84194-67-2; le (X = H; isomer l), 23439-91-0; le (X = H; isomer 2), 24867-90-1; le (X = Ac; isomer l), 23439-90-9; le (X = Ac; isomer 2), 84194-68-3; If (X = H; isomer l), 10531-50-7; If (X = H; isomer 2), 340-06-7; If (X = Ac), 84194-69-4; lg (X = H; isomer l), 20698-91-3; lg (X = H; isomer 2), 21210-43-5; l g (X = Ac), 947-94-4; lh (X = H; isomer l), 41822-67-7; lh (X = H; isomer 2), 5773-56-8 lh (X = Ac; isomer l), 84194-70-7; li (X = H isomer l), 5928-66-5; li (X = H; isomer 2), 5928-67-6; li (X = Ac; isomer l), 84275-456; li (X = Ac; isomer 2), 84275-46-7; lj (X = H; isomer l), 84275-47-8; lj (X = H; isomer 2), 66768-23-8; l j (X = Ac; isomer l), 84194-72-9; l j (X = Ac; isomer 2), 84194-73-0; l k (X = H), 4187-87-5; lk (X = Ac), 16169-88-3; 2a (X = H; isomer l), 42070-92-8; 2a (X = H; isomer 2), 51154-54-2; 2a (X = Ac; isomer l), 84194-74-1; 2a (X = Ac; isomer 2), 84194-75-2; 2b (X = H), (X = Ac), 945-89-1; 2d (X = H; isomer l), 1517-71-1; 2d (X = H; isomer 2), 2516-69-0; 2d (X = Ac; isomer l), 84194-76-3; 2d (X = Ac; isomer 2), 84194-77-4; 3 (X = H; isomer l), 13448-81-2; 3 (X = H; isomer 21, 13448-80-1; 3 (X = Ac), 55012-78-7; 4 (X = H; isomer l), 42177-25-3; 4 (X = H; isomer 2), 15914-84-8; 4 (X = Ac; isomer l), 16197-94-7; 4 (X = Ac; isomer 2), 16197-95-8; 5 (X = H; isomer l), 52193-85-8; 5 (X = H; isomer 2), 27544-18-9; 5 (X = Ac; isomer l), 84194-78-5; 5 (X = Ac; isomer 2), 8419479-6; 6 (X = H; isomer l), 84194-80-9; 6 (X = H; isomer 2), 84194-81-0; 6 (X = Ac; isomer l), 84194-82-1; 6 (X = Ac; isomer 2), 8419483-2; 8 (X = Ac; isomer l), 84194-84-3; 8 (X = Ac; isomer 2), 84194-85-4; 9a (X = H), 6351-10-6; 9a (X = Ac), 26452-982; 9b (X = H; isomer l), 84275-489; 9b (X = H; isomer 2), 57089-40-4; 9b/9c (X = Ac), 58540-44-6; 9c (X = H), 17496-18-3; 9d (X = H; isomer 11, 24867-97-8; 9d (X = H; isomer 2), 57018-62-9; 9d (X = Ac), 9g/9h (X = H), 67864-28-2; 9g/9h (X = Ac), 84194-87-6; 10a (X = H), 529-33-9; 10a (X = Ac), 21503-12-8; 10b (X = H; isomer l), 38157-18-5; lob (X = H; isomer 2), 65941-81-3; 10b/10c (X = Ac), 84194-88-7; 1Oc (X = H), 32281-70-2; 10d (X = H; isomer l), 24867-99-0; 10d (X = H; isomer 2), 84275-49-0; 10d (X = Ac), 84194-89-8; 1Oe (X = H; isomer l), 84275-50-3; 1Oe (X = H; isomer 2), 84275-51-4; lb/lOf (X = Ac), 84194-90-1; 10f (X = H; isomer l), 79465-07-9; 10f (X = H; isomer 2), 84275-52-5; log (X = H; isomer I), 84194-91-2; lOg (X = H; isomer 2), 84194-92-3; 10g/10h (X = Ac), 84194-93-4; 10h (X = H; isomer l), 84194-94-5; 10h (X = H; isomer 2), 84194-95-6; 11 (X 5: H), 84194-96-7; 11 (X = 13 (X = H; isomer l), 79465-08-0; 13 (X = H isomer 2), 27549-85-5; 13 (X = Ac; isomer l), 84275-53-6; 13 (X = Ac; isomer 2), 6531-13-1; 2b (X = Ac), 19759-27-4; 2~ (X = H), 3319-15-1; 2~ 7 (x = HI, 420864-4; 7 (x = AC), 22426-24-0; 8 (x = H), 2309-47-9; 54553-64-9; 9e/9f (X = H), 5400-80-6; %/9f (X = Ac), 84194-86-5; Ac), 84194-97-8; 12 (X = H), 7508-20-5; 12 (X = Ac), 84194-98-9; 65915-66-4.