Synthesis of hydrophenanthrenes through a ‘green’ Fischer carbene–alkyne coupling process Rongti Li, Lei Zhang, Alejandro Camacho-Davila and James W. Herndon * Department of Chemistry and Biochemistry, New Mexico State University, MSC 3C, Las Cruces, NM 88003, USA Received 11 May 2005; accepted 31 May 2005 Available online 15 June 2005 Abstract—Coupling of alkynylbenzoyl systems with c,d-unsaturated Fischer carbene complexes leads to the formation of hydro- phenanthrene derivatives. This reaction is not affected by aqueous systems, which offer a further advantage such that chromium hexacarbonyl sublimes during the reaction process. Chromium carbene–alkyne coupling processes can thus be performed in envi- ronmentally friendly solvents with substoichiometric net consumption of chromium hexacarbonyl. Ó 2005 Elsevier Ltd. All rights reserved. A novel two-component stitching of the hydrophen- anthrene ring system via the reaction of alkynylbenz- aldehyde derivatives with c,d-unsaturated carbene com- plexes has recently been developed in this laboratory (e.g., conversion of 1a+2b to 5b in Scheme 1). 1 The reac- tion proceeds with a high degree of diastereo-selectivity when chiral c,d-unsaturated carbene complexes (e.g., 2b) were employed to afford a single compound (e.g., 5b) in good yield. The analogous reaction using simple bute- nylcarbene complex 2a is considerably less efficient than the more highly substituted examples presented in Refs. 1a–c, 2 and afforded a low yield of a mixture of com- plexed and uncomplexed derivatives after silica gel chro- matography. As part of a general effort to prepare hydrophenanthrene natural products (including mor- phine alkaloids and abietanes) using the reaction in Scheme 1, the coupling of highly oxygenated alkynyl- benzoyl derivatives (e.g., 1c, Scheme 2) with simple c,d-unsaturated carbene complexes was tested. The most satisfactory yield optimization experiment involved the deliberate addition of water to the reaction mixture. 3 When the coupling of alkynylbenzaldehyde 1c and car- bene complex 2a was conducted in 19:1 dioxane–water, the yield of hydrophenanthrene 5c was higher than in any other experiment and chromium hexacarbonyl was deposited onto the condenser. Since carbene complex 2a was originally prepared from chromium hexacarbonyl (see Scheme 3), the net effect is that the overall transformation is substoichiometric in chromium. In this letter, these two effects will be ex- plored in more depth. The ultimate goal is to devise a system where chromium carbene complexes couple with an alkyne in a process that employs cheap and environ- mentally friendly solvents with minimal net consumption of chromium. 4 Although alkylation of chromium carbene complex stabilized anions, 5 synthesis 0040-4039/$ - see front matter Ó 2005 Elsevier Ltd. All rights reserved. doi:10.1016/j.tetlet.2005.05.126 Keywords: Carbene complexes; Alkynes; Isobenzofurans; Diels–Alder reaction; Aqueous reactions. * Corresponding author. Tel.: +1 505 6462487; fax: +1 505 6462649; e-mail: jherndon@nmsu.edu Scheme 1. Tetrahedron Letters 46 (2005) 5117–5120 Tetrahedron Letters