Ruthenium-Catalyzed [2 + 2] Cycloadditions between Norbornene and Propargylic Alcohols or Their Derivatives

Abstract

Diastereoselective ruthenium-catalyzed [2 + 2] cycloadditions of norbornene and propargylic alcohols or their derivatives were investigated. The cycloadditions were found to be highly stereoselective, giving exo cycloadducts in moderate to excellent yields with diastereoselectivities up to 92:8. When a chiral propargylic alcohol was used in the cycloaddition, up to 80% ee of the [2 + 2] cycloadducts was observed after oxidation of the alcohol. ■ INTRODUCTIONThe development of ruthenium-catalyzed chemical processes has become an emerging field over the past decade. 1−4 With their wide range of oxidation states (from −2 to +8) and several coordination geometries, ruthenium catalysts can form a variety of intermediates such as (π-allyl)ruthenium, 5 ruthenium− carbene, 6 and ruthenacycle species. 7 Among various ruthenium complexes, CpRu(COD)Cl and Cp*Ru(COD)Cl have been found to be the catalysts of choice in many reactions such as [2 + 2 + 2] cycloadditions, 8−10 conjugate additions, 11 bis-Diels− Alder cycloadditions, 12 Alder-ene reactions, 13,14 cross-benzannulations, 15 and many others. 1,2 We and other groups have been largely involved in the preparation of cyclobutene rings via ruthenium-catalyzed [2 + 2] cycloadditions. 16−28 Although asymmetric versions of transition-metal-catalyzed cycloaddition reactions such as [4 + 2], 29 [2 + 2 + 1], 30,31 [2 + 2 + 2], 32,33 and [4 + 2 + 2] 34 have been recognized, to the best of our knowledge, very few studies on the asymmetric transition-metalcatalyzed [2 + 2] cycloadditions between an alkene and an alkyne have been reported in the literature. We have demonstrated the first examples of asymmetric induction studies in rutheniumcatalyzed [2 + 2] cycloadditions between symmetrical bicyclic alkenes and alkynes bearing a chiral sultam auxiliary, achieving excellent levels of asymmetric induction after recovery of the chiral auxiliary (eq 1). 35 More recently, rhodium-catalyzed enantioselective [2 + 2] cycloadditions of alkynyl esters and norbornene derivatives have been reported, demonstrating excellent enantioselectivity using a chiral rhodium catalyst (eq 2). 36 In our preliminary communication 19 we reported a diastereoselective ruthenium-catalyzed [2 + 2] cycloaddition between bicyclic alkenes and chiral alkynes 2a−f (Table 1). In this full paper, we have identified the previously undetermined structures of the major diastereomers, and have expanded our investigation to the effects of propargylic and acetylenic substituents on the diastereoselectivity of cycloaddition (Tables 2 and 3). The use of homopropargylic alcohols as the alkyne partner in the Rucatalyzed cycloaddition has also been demonstrated (Table 4).

Synthesis of Homoverrucosanoid-Derived Esters and Evaluation as MDR Modulators

“…The diene 5a was made available in four steps and on gram scale starting from commercially available 1,2-cyclohexanediol . Initially, we selected the known alkyne dienophiles 6 , , 7 , 8 , and 9 , featuring constitutionally differentiated end groups for exploratory studies of the chemo- and site-selectivity of the envisioned (4 + 2)-cycloaddition (Scheme ).…”

“…The ratio of C1 epimers was determined by integration of the 1 H NMR signals at 1.31 ppm (major epimer) and 1.29 ppm (minor epimer): R f 0.29 (cyclohexane− ethyl acetate 2:1); 1 H NMR (CDCl 3 , 600 MHz) δ 1.29 (d, J = 6.6 Hz, 3H minor ), 1.31 (d, J = 6.6 Hz, 3H major ), 1.33 (s, 3H major +3H minor ), 1.39 (s, 3H minor ), 1.40 (s, 3H major ), 1.78−1.94 (m, OH major +OH minor ), 2.45− 2.52 (m, 1H major +1H minor ), 2.53−2.62 (m, 1H major +1H minor ), 4.38 (q, J = 6.6 Hz, 1H major ), 4.39 (q, J = 6. 6 ), 66.7 (CH major ), 67.0 (CH minor ), 78.15 (CH major ), 78.20 (CH minor ), 85.15 (CH minor ), 85.20 (CH major ), 109.8 (C minor ), 109.9 (C major ), 123.4 (CH minor ), 123.6 (CH major ), 150.3 (C major ), 150.5 (C minor ); IR ν 3420, 2980, 2930, 1370, 1205, 1155, 1035, 865 cm −1 ; HRMS (ESI) m/z could not be detected. A copy of the HRMS spectrum is provided as part of the Supporting Information.…”

Ruthenium-Catalyzed Asymmetric [2 + 2] Cycloadditions between Chiral Acyl Camphorsultam-Substituted Alkynes and Bicyclic Alkenes

“…The identical protection-reduction sequence was applied to the racemic ester adduct 8q , producing the same alcohol. The high level of asymmetric induction observed in this instance could arise from a stabilizing intramolecular hydrogen-bonding interaction between the alcohol oxygen of alkyne 12s and the chloride of the Cp*RuCl(cod) catalyst, which has been investigated in cycloaddition studies involving propargylic alcohols. , …”

Synthesis and Diels–Alder Reactivity of Substituted [4]Dendralenes

“…Pent-2-yne-1,4-diol (22). 39 The title compound 22 was prepared following the procedure reported by Takahashi and Matsumoto. 40 (E)-Diethyl-3-ethylidene-4-methylenehexanedioate ( 23) and (Z)-Diethyl-3-ethylidene-4-methylenehexanedioate (24).…”