Rotational selectivity in cyclobutene ring openings. Model studies directed toward a synthesis of verrucarin A

Abstract

3.26 g of 26; 95% recovery) showed a resonance (6 3.68) only for methanesulfonyl chloride (26). Treatment of the aqueous phase with benzylthiuronium chloride gave neither benzylthiuronium methanesulfinate nor benzylthiuronium methanesulfonate (absence of methanesulfinic acid (24) and methanesulfonic Attempted Reaction of S-Methyl Methanesulfonothioate (12) with Activated Zinc at 0 "C. The experimental procedure described above for zinc and methanesulfonyl chloride (26) at 0 "C for 1 h was repeated except thiosulfonate 12 was substituted for 26.". After the workup, ' H NMR analysis showed the presence of 12 (92% recovery). Treatment of the aqueous phase with benzylthiuronium chloride did not produce a precipitate (absence of methanesulfinic acid (24) and methanesulfonic Attempted Reaction of S-Methyl Methanesulfonothioate (12) with Anhydrous Zinc Chloride at 0 OC. A 10-mL round-bottomed flask fitted with a serum stopper and containing 0.61 g (4.10 mmol) of anhydrous zinc chloridel8 and a magnetic stirring bar was placed in an ice bath. Dry ether (1 mL) waa added via syringe to the flask. To this solution was added via syringe under nitrogen flow 0.51 g (4.10 mmol) of S-methyl methanesulfonothioate (12) in 2 mL of dry ether. The solution was stirred 1 h at 0 "C, the reaction solution was washed with 15 mL of saturated ammonium chloride salution, and the organic layer was dried (Na2S04). After removal of the solvent in vacuo, 'H NMR showed only the presence of thiosulfonate 12. No compounds were detected in the aqueous layer from the saturated ammonium chloride wash.Attempted Reaction of Methanesulfinyl Chloride (2) with Anhydrous Zinc Chloride at 0 OC. A small amount of anhydrous zinc chloride'* was added to a solution of methanesukinyl chloride (2) in CDC13 in a 5-mm NMR tube. The 'H NMR and I3C NMR spectra were taken as soon as possible after addition. The 'H NMR spectrum was taken again after the solution was kept at 22-24 O C for several hours. All spectra showed the presence of only methanesulfinyl chloride (2). Stability of Methanesulfinyl Chloride (2) in the Absence of Activated Zinc.A solution of 2.96 g (30 mmol) of methanesulfinyl chloride (97.5% 2 and 2.5% 26) in 12 mL of dry ether was syringed into a flame-dried, nitrogen-flushed, 25-mL, round-bottomed flask containing a magnetic stirring bar. After the solution was stirred for 1 h at 0 "C under dry nitrogen, the ether was removed in vacuo. Proton NMR analysis of the residue in CDC13 showed the presence of only methanesulfinyl chloride (2, 97.5%) and 26 (2.5%).The rotational selectivity in the opening of dissymmetric cyclobutenes to the corresponding dienes is described. In the opening of the monoesters of cis-3,4-cyclobutenedicarboxylic acid, an unusual solvent effect on the ring opening is noted. Switching from Me@O to 1,2-dichloroethane leads to a 3:l ratio of the (E,Z)-muconates, favoring the ester on the E double bond. The two isomers can be differentiated by 13C NMR spectroscopy in which the above isomer shows a A6 for the a,a' carbons of only -2....

Oxoanion Binding by Guanidiniocarbonylpyrrole Cations in Water: A Combined DFT and MD Investigation

“…One of these enantiomers was also available by enzymatic oxidation of diol 3a 15. Diesters and monoesters 7 – 8 were prepared from 1 either as racemates1d,8,16,17 or – for (+)‐8 – as the nonracemate 14a,18. In the case of 7c an alternative route from 1,3,5,7‐cyclooctatetraene has been proposed 19.…”

“…This would increase the effective bulk of this substituent, resulting in its preferential outward rotation, in contrast to reactions carried out in CCl 4 or CH 2 ClCH 2 Cl. Influence of secondary orbital interactions was also envisioned 17. Over the years it became evident that numerous results could not be interpreted only in terms of steric effects, and theoretical works on these ring openings by Houk’s group22 showed that orbital interactions within the transition state tend to favor outward rotation in the case of π‐donor groups and inward rotation in the case of π‐acceptor substituents.…”

Stereoselective Construction of (E,Z)‐1,3‐Dienes and Its Application in Natural Product Synthesis

“…An alternative, electrocyclic ring-opening strategy has been illustrated by Trost, where a cis cyclobutene ring opening approach was used for the total synthesis of verrucarin A. [11] Starting from macrocyclic compound 8, a 2:1 mixture of the two E,Z-isomers (9 and 10) was obtained (Scheme 3, eq (a)). Later, Wallace described the electrocyclic ring opening of cis cyclobutenecarbaldehyde 11 (Scheme 3, eq (b)).…”

Synthesis of New unnatural Macrocyclic Trichothecenes: 4‐epiverrucarin A. 47th Communication on verrucarins and roridins

“…I2.13-Epoxy-4a-hydronytrichothec-9-en-15-yl Acetate (23 (13) (14)); 1.73 (s, CH3(16)); 2.03 (m. CH2 (7), CH2(8)); 2.49 (m, H-C(3)); 2.81, 3.10 (AB, J = 4, CH2 (13) …”

“…This result suggests that the macrolidic part possesses a cytotoxic activity independent of the epoxybearing trichothecene moiety. The cytotoxic activities of macrocyclic trichothecene mode1 compounds which do not possess the trichothecene moiety support this hypothesis [23]. However, with the data available at present, it is too early to draw final conclusions for the structural requirements for the biological activity of trichothecene mycotoxins.…”