Synthesis of new chiral alkenyl Fischer carbene complexes

New chiral group 6 Fischer alkoxycarbene complexes 1 and 2 have been synthesized by condensation of enantiopure aldehydes 6 and 7 , respectively, with methylcarbene complexes 5 . The corresponding aminocarbene complexes 3 and 4 were accessible from 1 and 2 by methoxy-pyrrolidine exchange. The chromium carbene 1b underwent the benzannulation reaction with alkynes affording chiral substituted phenols 11


Introduction
Since their discovery by Fischer 1 et al. in 1964, Fischer carbene complexes have emerged as powerful organometallic reagents in organic synthesis. 2Among the Fischer carbene complexes, α,β-unsaturated carbenes have been demonstrated to be particularly attractive for synthetic purposes because of their polyfunctional and versatile character. 3n the other hand, the development of asymmetric processes based on chiral alkenyl Fischer carbene complexes have received increasing attention. 4Although incorporation of the chiral auxiliary at the ligands, e.g.chiral phosphines 5 and phosphites, 6 appears to be the ideal strategy for asymmetric synthesis, it has not been successfully implemented as a practical protocol.On the contrary, a number of efficient enantioselective syntheses using group 6 metal carbene complexes derived from chiral alcohols, 7 amines, 8 aminoalcohols, 9 oxazolines, 10 etc. have been reported to provide rapid access to optically active open-chain and cyclic molecules. 11Finally, carbene complexes with attached sugars are being studied by the group of K. H. Dötz. 12 Here we report the synthesis of new chiral alkenyl Fischer carbene complexes 1-4 (Figure 1) derived from optically active reagents that are readily available from the natural chiral pool.The presence of the chiral center at the β-position is expected to induce high selectivity, especially in the case of reactions initiated at that position.Moreover, this inductive effect would complement that provided at the carbene carbon by the chiral alkoxy group in carbene complexes derived from chiral alcohols.

Results and Discussion
Alkoxycarbene complexes 1 and 2 were synthesized by condensation of the pentacarbonyl[methoxy(methyl)]carbene complexes 5 and aldehydes 6 and 7 (Figure 2).Aldehydes 6 and 7 were readily prepared from commercially available 1,2:5,6-diisopropylidene-D-mannitol 13 and (S)-malic acid 14 , respectively, following well known procedures.The condensation of enolizable aldehydes with α-deprotonated carbene complexes is more problematic than with non-enolizable ones 15 and usually requires a Lewis acid. 16Moreover, the rapid polymerization of aldehydes 6,7 prevents the use of Lewis acids.The synthesis of the alkoxyalkenylcarbene complexes 1,2 was actually achieved by diazabicycloundecane (DBU) deprotonation of the carbenes 5, followed by stirring at 0°C with freshly distilled aldehydes 6 or 7.The diastereomeric mixtures of 8 and 9, respectively, thus obtained were not isolated but reacted with methanesulfonyl chloride and triethylamine to induce the α,β-elimination and to provide the desired carbene complexes 1a,b and 2 (Scheme 1).In order to determine the reactivity of the new Fischer carbene complexes, the alkoxy-amine exchange and the relevant Dötz benzoannulation 17 reactions were studied.First, the alkenyl(methoxy)carbene complexes 1a and 2 smoothly reacted with pyrrolidine to afford new chiral aminocarbene complexes of chromium and tungsten 3 and 4, respectively, in good yields (Scheme 2).It was satisfying to find that the chromium carbenes are as reactive as conventional analogs toward alkynes, being appropriate chiral organometallic reagents for the benzannulation reaction.Thus, heating the carbene complex 1b with alkynes 10a,b at 60°C resulted in the regioselective formation of the chiral substituted phenols 11a,b in acceptable yields (Scheme 3).Apart from their importance as optically active materials, interesting applications, for instance as tripod-type ligands, 18 can be envisioned for these cycloadducts due to the presence of various differentiable hydroxy functionalities.

Conclusions
We have described a convenient synthesis of a new type or chiral pentacarbonylalkenylalkoxy and amino Fischer carbene complexes from easily accessible reagents.The new complexes appear to be reactive through either the carbene carbon or the β-carbon positions.Further applications of these complexes in enantioselective synthesis are being performed in our laboratory and will be reported in the near future.

Experimental Section
General Procedures.All reactions and purifications, except 11, were carried out under an atmosphere of dry N 2 .TLC was performed on aluminium-backed plated coated with silica gel 60 with F 254 indicator (Merck).Flash column chromatography was carried out, under nitrogen atmosphere, on silica gel 60 and solvents used for the chromatographic purification of the carbene complexes was previously deoxygenated and saturated with N 2 . 1 H ( 13 C)-NMR spectra were recorded at 200 (50) or 300 (75) MHz on Brucker instruments.High-resolution mass spectra (HRMS) were performed on a Finnigan MAT 95 spectrometer.All commercially available reagents were used without purification unless otherwise indicated.

General procedure for the synthesis of the aminocarbenes 3, 4
A solution of alkoxycarbenes 1,2 (2 mmol) in 20 ml of dry diethyl ether was cooled to -30°C and pyrrolidine (2,2 mmol, 160 mg) was added.The mixture was removed from the cooling bath and stirred at room temperature for 30 minutes.Removal of the solvent under vacuo (10 -2 torr.) and chromatographic purification yielded the aminocarbene complexes 3,4 as yellow oils.