Intramolecular Dotz reaction

The intramolecular DOtz reaction, in which the alkyne is tethered to the carbene, improves synthetic efficiency and regiocontrol, although internal alkynes work better than terminal alkynes [30], Such cycloadditions provided the kqr to a synthesis of the antibiotic deoxy-frenolicin [Eq. (12)] [31] and played a role in work aimed toward the synthesis of the ben-zofuran angelicin, in which a 3-furylcarbene complex aimulates toward C2 of the furan, avoiding forming an isobenzofuran structure [Eq. (13)] [32]. 

Fischer-type chromium carbene complexes with 1-ethoxycyclopropylalkynyl substituents at the carbene carbon, e.g. 25, on reaction with dimethylamine and subsequent conversion of the resulting vinylcarbene with alkynes surprisingly did not give phenol derivatives, as would be expected from the known Dotz reaction, but gave cyclopenta[ )]pyrans, e.g. 26. The reaction is interpreted as a double alkyne-insertion/CO-insertion sequence with formation of a trienylketene intermediate, which undergoes intramolecular hetero-Diels-Alder cycloaddition and dimethylamine elimination. ... 

Substitution of CO by phosphines 145 The Dotz reaction 149 Rearrangement reactions with loss of CO 151 Photochemical reactions 153 Reactions at the carbene carbon 158 General features 158 Amine nucleophiles 159 Phospine and phosphite nucleophiles 167 Alcohols and alkoxide ion nucleophiles 171 Thiol and thiolate ion nucleophiles 179 Intramolecular nucleophilic reactions 191 Hydroxide ion and water as nucleophiles 194 Insertion reactions initiated by nucleophilic attack Acid-base reactions at the a-carbon 207 General features and methods 207 Kinetic and thermodynamic acidities 209 Effect of structure on pKa values 210 Intrinsic rate constants for proton transfer 219 Thermodynamic acidities in organic solvents 223 Hydrolysis of ionizable carbene complexes 228 Acknowledgments 232 References 233... 

The Dotz reaction may employ heteroaryl substituted carbenes. The fiuyl carbene 8.58 gave thebenzofuran 8.59 (Scheme 8.19). The reaction may also be intramolecular, taking advantage of the acylation of the ate complex 8.60 to introduce the alkyne (Scheme 8.20). ... 

The Dotz benzannulation reaction, based on the alkyne cycloaddition to chromium carbene complexes, is the most important application of Fischer carbene complexes. Among the various Fischer carbene complexes, alkoxy and aminocarbene complexes of chromium undergo a novel inter- and intramolecular tandem alkyne insertion/ carbene annotation sequence to give 9H-carbazoles and nf/-benzo[fl]carbazoles. 

The two syntheses of 11-deoxydaunomycinone are summarized in Schemes 38 and 39 as they are illustrative of the viability of carbene complexes as intermediates in organic synthesis. The synthesis by Dotz and Popall begins with the chelated o-methoxyphenyl carbene complex (275) and the alkyne (276). A single regioisomer of the phenol (277) was obtained in 76% yield in the benzannulation. After protection of the phenol and carbon homologation of the ketone to the acid, an intramolecular Frie-del-Crafts reaction gave the tetracyclic dione (279) in 45% overall yield from (277). This represents a formal synthesis of 11-deoxydaunomycinone (269) since it has been reported that (279) can be converted to (269) by the procedures of Sih and Johnson. ... 

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