Synthesis of 4,5-trans-Substituted Cyclohexenones

Abstract

Dearomatization of anisole chromiumtricarbonyl by sequential regio-and diastereoselective addition of a C-nucleophile and a C-electrophile is problematic because of competitive orthodeprotonation. A solution is offered by carrying out the reaction sequence with the bis ortho silylated complex. Decomplexation and acid work-up affords 4,5-trans-disubstituted cyclohexenones.Partially unsaturated, substituted six-membered ring compounds are useful intermediates in organic synthesis and are often prepared by Diels-Alder reaction. 1 An alternative approach is by arene dearomatization via temporary complexation to the electrophilic chromiumtricarbonyl group, and a one-pot sequential trans-addition of two Cfragments across an arene bond. 2The vicinal stereocontrol and the development of successful diastereoselective and enantioselective variants of this transformation make it attractive for synthesis. 2 However, while widely applicable to complexes of benzene, phenyl oxazolines, and benzaldehyde imines, it appears that application to anisole complexes is problematic linked to reversible nucleophilic addition and competitive lithiation. Both of these processes lead to poor conversion and low yields of products. This communication presents an alternative that overcomes this problem.Chromiumtricarbonyl complexes of both anisole and chiral alkyl phenol ethers have been successfully converted to synthetically useful 5-substituted cyclohexenones via a nucleophile addition-protonation. 2e,3 The metaregioselectivity of nucleophilic addition to 1 has been interpreted on the basis of charge and/or orbital control. 4 However, reversibility of nucleophilic addition to 1 has been demonstrated by double cross-over experiments 5 and meta-regioselectivity in 1 can be correlated to the stability of the anionic cyclohexadienyl intermediate. 6The scarcity of examples 7 of sequential addition of two Cfragments to the anisole complex 1 can be attributed to the reversibility of nucleophilic addition on one hand and to the competition reaction of ortho-lithiation by reactive organolithium compounds on the other (Scheme 1). 8In our hands, reactions of 1 with allyl-, vinyl-, methyl-or phenyllithium as nucleophile and propargyl bromide as electrophile followed by acid work-up gave 2 in low yield (<10%). The reaction of vinylLi with 1 in THF at -78°C was followed by in situ monitoring of the infrared spectra (n CO absorptions) of intermediates in solution. 9 Over a period of two hours, new IR bands at 1930 cm -1 and 1837 cm -1 grew in at the expense of the n CO bands associated with the starting complex (1961, 1879 cm -1 ). Based on comparison of data from the sequential lithiation-electrophile trapping, 4,10 the new bands were assigned to 4. Addition of N,N¢-dimethylpropyleneurea (DMPU) 11 resulted in a very rapid change to a spectrum characteristic of an anionic cyclohexadienyl complex. 12 Addition of TMSpropargyl bromide afforded 5. When the reaction was repeated with DMPU present from the start, 5 was again the sole product isolated (57%).Sche...

A Synthetic and Mechanistic Investigation of the Chromium Tricarbonyl-Mediated Masamune–Bergman Cyclization. Direct Observation of a Ground-State Triplet p-Benzyne Biradical

“…This unsaturated species will reversibly complex enediyne through the alkene moiety in preference to the alkyne (27). The labile THF ligands dissociate to allow complexation of the alkyne termini (28), subsequently decreasing the c−d distance. Direct C1−C6 bond formation occurs to yield the singlet biradical species 29, which is then rapidly quenched by hydrogen atom abstraction through a cage-type mechanism to yield the final product 32.…”

“…Vibrational analyses were carried out to confirm the nature of all stationary points and to calculate the thermal corrections (enthalpy and entropy) for 298 K, 1 bar, gas phase. The following compounds were prepared by published procedures: 2,6-bis(trimethylsilyl)anisole ( 10 ), [Cr(CO) 3 (η 6 -2,6-bis(trimethylsilyl)anisole)] ( 11 ), ( Z )-5-chloropent-4-en-2-yn-1-ol, ( Z )-1,6-bis(trimethylsilyl)hexa-3-en-1,5-diyne 7b , ( Z )-tetradeca-7-en-5,9-diyne ( 19 ), [RuCp*(MeCN) 3 ]PF 6 , and [Cr(CO) 3 (η 6 -C 10 H 8 )] ( 9 ) …”