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

Synthesis of Macrocyclic Lactones by Ring Enlargement Reaction Treatment of 3‐(1‐nitro‐2‐oxocyclohexyl)propanal (1) prepared by Michael addition of 2‐nitrocyclohexanon and acrylaldehyde with methyltri (2‐propoxy)tita‐nium yielded a mixture of 2 and 3 which was converted into 6‐nitro‐9‐decanolide (4).

Synthesis of Bicyclo[3.3.0Joct-l(5)en-2-one from Cyclohexanone SummaryTreatment of 2-nitrocyclohexanone (2) with acrylaldehyde yielded in the presence of tetrabutylammonium fluoride the bicyclic product 5, which was oxidized to the nitro-diketone 3. The conversion of 3 to the title compound 1 was achieved in nearly quantitative yield under unusual conditions: K,CO,/H,O and H,SO,. Compound 3 was also converted to 1 (stepwise and one-pot reaction, respectively) by treatment with 1. NaOCH,, 2. TiCl,, and 3. H,SO, (Scheme).

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Crystal structures have been determined of methyl trans-1 -hydroxy-6-nitro-3-oxobicyclo[4.4.0]decane-2-carboxylate (19), cis-3-methyl-6-nitro-2-oxabicyclo[4.4.O]decan-1-01 (2), cis-7-hydroxy-1 -nitrobicyclo[5.4.0]undecan%one (13), and the medium-ring compounds 2-acetyl-4-nitrocyclooctanone (9), methyl 5-nitro-2-oxocyclooctanecarboxylate (4), 2-acetyl-4-nitrocyclononanone (ll), 2-acetyl-4-nitrocyclodecanone (15), benzyl 5-nitro-2,1 l-dioxocycloundecanecarboxylate (24), methyl 5-nitro-2,12-dioxocyclododecanecarboxylate (21), and 8-nitro-11 -oxo-13-tridecanolide (7), which are intermediates, side products, or end products of the 'Zip' ring-enlargement reaction. The conformations of most of the medium-ring compounds are very similar to equal-sized ring compounds previously determined by other authors. ~ ~In the past, a new method for ring enlargement by the so-called 'Zip' reaction was developed by which a number of new polyaminolactams were synthesized starting from lactams [ 11. The same reaction principle was followed to convert carbocyclic compounds 2,Part of the thesis of K. K. ') Postdoctoral fellow 1980182.