The Carbon Zip Reaction: A Method for Expanding Carbocycles

Abstract

SummaryA general method for enlargement of carbocyclic rings by the so called zip reaction is given. The Michael adducts of 2-nitrocycloalkanones with 3-0x0-4-pentenoates in the presence of tetrabutylammonium fluoride give in high yield compounds with the ring enlarged by four C-atoms. By this method 7-, 8-, and 12-membered cycloalkanones were converted respectively to 11-, 12-, and 16-membered functionalized carbocycles (see Scheme 2 and 3).In the last few years a large number of natural products with medium and large rings, mainly ketonic or lactonic, have been identified. The pharmacological importance of these compounds has resulted in much synthetic work (cJ: [l]). In order to develop a general pathway for their synthesis we have tried to use the zip reaction [2] to enlarge normal and medium rings [3]. We now describe a method to produce medium and large ring ketonic of lactonic compounds by incorporation of four C-atoms in one step.The cyclohexyl Michael adduct 2, prepared from 1 and methyl vinyl ketone, added to t-BuOK (2 mol-equiv.) in THF at -80" yielded cyclooctyl compound 3 (85%) (see Scheme I) which produced a strong dark violet color with ferric chloride. The 'H-NMR. spectrum of this product contains a m at 4.68-4.27 (H-C(4)), a d at 3.01 (H-C(3), a s at 2.02 (CH3CO) and a s at 16.93 ppm (enolic OH). A broad absorption at 1760-1590 cm-', characteristic of an enolic 1,3-diketone was observed in the IR. spectrum. In the I3C-NMR. spectra, the s at 96.3 ppm (C(2)) in the spectrum of 2 was lost in the spectrum of 3, while new signals appeared at 104.7 ppm (C(2), s, enol form) and 86.7 (d, C(4)). These observations are consistent with cleavage of the C(l),C(2)-bond in 2. The carbonyl resonances were also shifted from 205.8 and 200.3 ppm in 2 to 193.9 and 193.3 ppm in 3. The physical data indicate that 3 exists in the enol form [4].Several unrecognizable products were obtained when the cycloheptyl adduct 5, prepared from 4, or the cyclooctyl adduct 10, prepared from 9, were treated in a manner similar to 2. However, addition of a THF solution of t-BuOK to 5 in THF (ix., the reverse of the preceding experiment) afforded two main products with positive ferric chloride tests on TLC. The cyclononyl compound 6 (44%) gave a violet color with ferric chloride, while the cycloundecyl compound 7 (35%) gave a

A New Approach to Erythrinanes through Pummerer-Type Cyclization

“…26a was unambiguously determined by NOE experiments, which showed a 4% signal enhancement at axial proton 3-H when 1-H was irradiated. After extensive experimentation, it was found that replacement of DBU by nBu 4 NF [28] gave adducts 26a and 26b as a 1:1 mixture of isomers in a combined yield of 68%, in a more reproducible manner. The stereochemical outcome of the key Michael addition has been demonstrated to be the result of kinetic control since separated isomers were recovered unchanged when re-exposed to the reaction conditions (Scheme 3).…”

Synthese von N‐(4‐Aminobutyl)‐16‐aza‐19‐nonadecanlactam und N‐(4‐Aminobutyl)‐17‐aza‐20‐icosanlactam (Desoxoinandenin)

“…Im ersten Schritt wird ein geeignet substituiertes [6] 13-bzw. 12-gliedriges Cycloalkanon-Derivat durch Ringerweiterung urn vier Glieder zum 17-bzw.…”

“…Nach Zugabe von 20 ml H 2 0 wurde rnit CH2C12 extrahiert, der Extrakt getrocknet, eingedampft und der Ruckstand chromatographiert (CH,CI,/MeOH 98:2): 1,16 g (55%) 7, farbloses 0 1 . IR: 1625IR: , 1600IR: , 1545IR: , 1330IR: , 1155IR: , 1090 ,6;143,3;143,l;142,8;137,O;136,6;135,9;135,7;135,l;130,2;130,l;129,7;129,5;129,l;128,9;128,8;46,2;45,9;45,8;44,7;433;43,l;42,6;42,3;36,O;33,9;33,8;…”

Nitrocompounds as useful reagents for the synthesis of dicarbonyl derivatives

“…This procedure represents one of the most exploited methods to prepare such difunctionalized derivatives that find a number of applications in the synthesis of important target molecules. The Michael addition of nitroalkanes to electron-poor olefins can be realized using basic promoters such as DBU, 27 TMG, 28 triphenylphospine, 29 fluoride salts 30 and hydroxide (alkoxide) anions. [31][32][33][34] Besides these procedures that work in homogeneous conditions a number of methods using basic catalysts that operate in heterogeneous systems can be employed profitably to carry out a conjugate addition.…”