Switching from the Myers reaction to a new thermal cyclization mode in enyne-allenes

A McMurry Route to the Dienediyne Portion of Models of the Neocarzinostatin Chromophore

“…Flash chromatography (pentane/diethyl ether, 3:1q1:1) on deactivated silica gel (pretreated with 25% aq. NH 3 ) afforded the title compound (18.8 mg, 76% (14) ,9-diene-2,7-diyn-4-one (33): At 0°C alcohol 32 (18.8 mg, 0.0831 mmol) was added to a stirred mixture of the Dess-Martin periodinane (88.1 mg, 0.208 mmol, 2.5 equiv. ), molecular sieves (4 Å ), and NaHCO 3 (one spatular tip-full, each) in CH 2 Cl 2 (3 ml …”

“…Flash chromatography (petroleum ether Ǟ petroleum ether/tert-butyl methyl ether, 10:1 Ǟ 1:1) of the residue afforded the title compound (10.5 g, 99%) as a colorless oil. (28) was prepared in a similar manner as 29 from 24 (11.1 g, 31.5 mmol) and isolated as a colorless liquid (7.42 g, 84% (14) ,9-diene-2,7-diyn-4-ol (32): At 0°C HF/pyridine complex (0.30 ml, 27 mg, 0.72 mmol, 6 equiv.) was added to the silyl ether 11 (37.2 mg, 0.109 mmol) in THF (5 ml) and the resulting solution stirred for 3.5 h. The reaction mixture was diluted with diethyl ether (5 ml) and hydrolyzed with H 2 O (5 ml).…”

“…Flash chromatography (petroleum ether/tert-butyl methyl ether, 5:1 Ǟ 1:4) of the residue afforded the title compound (462 mg, 98%) as a yellow oil. (14) ,9-diene-2,7-diyne (11): Cl 3 Ti(DME) 2 was prepared by refluxing TiCl 3 (1.39 g, 9.01 mmol, 43 equiv.) in freshly distilled DME (30 ml) for 1.5 d. Zn/Cu couple (2.20 g, 33.8 mmol, 160 equiv.)…”

“…Transannular overlap of their in-plane π orbitals initiates cycloaromatizations giving the styrene-α,meta-biradicals 3 which damage DNA as sketched above. Such cycloaromatizations 5 Ǟ 6 can be differentiated as "neocarzinostatin-type cycloaromatization" from the "Bergman cyclizations" of 3-hexene-1,5-diynes to benzene-1,4-biradicals, [12] the "Saito-Myers cyclizations" of enyneallenes to toluene-α,meta-biradicals [13] or their "Schmittel cyclizations" to pentafulvene-based biradicals, [14] the "Moore cyclizations" of enyneketenes to phenoxyl biradicals, [15] and NicolaouЈs cyclization of diallenylsulfones to thiophene-S,S-dioxide based 1,4 biradicals. [16] The protein-free neocarzinostatin chromophore 1 is exceedingly labile.…”

Straightforward syntheses of biradical-producing bicyclic dienediynes—dienediyne ketones cycloaromatize ia the Saito–Myers and not ia the neocarzinostatin pathway

“…In 1989, Saito and Myers and their respective coworkers recognized that 6-heptyne-1,2,4-trienes (from now on " enyneallenes Ï, 3) can also cycloaromatize (" SaitoÈMyers cyclization Ï, Scheme 1).4 They thereby form short-lived toluene-a,meta biradicals 4, which abstract hydrogen atoms from easily oxidizable compounds (1,4-cyclohexadiene, thiols or DNA) to give toluenes 6. SaitoÈMyers cyclizations have since then been encountered in many enyneallenes 3,5 including enynallenyl ketones 3a,b.6h16 Recently, Schmittel et al 17 and Gillmann et al 18 found that some enyneallenes 3 undergo * Fax : ]49-551-392944 ; E-mail : rbrueck=gwdg.de ¤ Fax : ]49-531-3915388 ; E-mail : R. Herges=tu-bs.de a di †erent biradical-producing cyclization reaction, furnishing fulvene-1,3-diyls 5 (" Schmittel cyclization Ï). This increasingly observed19 reaction mode is not a cycloaromatization and in this regard is distinct from Bergman, neocarzinostatin and SaitoÈMyers cyclizations.…”