Ketones intramolecular coupling

The reductive coupling of aldehydes or ketones with 01, -unsaturated carboxylic esters by > 2 mol samarium(II) iodide (J.A. Soderquist, 1991) provides a convenient route to y-lactones (K. Otsubo, 1986). Intramolecular coupling of this type may produce trans-2-hy-droxycycloalkaneacetic esters with high stereoselectivity, if the educt is an ( )-isomer (E.J. Enholm, 1989 A, B). 

The 1,5- and 1,6-dialdehydes 22 and 24 undergo the annulative pinacol coupling to give the cyclic vzc-diols 23 and 25, respectively (Scheme 13) [29]. The vanadium-catalyzed intramolecular coupling reaction of 1,5-diketone 26 also proceeds with excellent selectivity (Scheme 14) although the intermolecular coupling of ketones such as acetophenone results in low diastereoselectivity under these conditions [21]. 

Several examples of transition metal catalysis for the synthesis of piperidines appeared this year. Palladium catalyzed intramolecular urethane cyclization onto an unactivated allylic alcohol was described as the key step in the stereoselective synthesis of the azasugar 1-deoxymannojirimycin . A new synthetic entry into the 2-azabicyclo[3.3.1]nonane framework was accomplished through a palladium mediated intramolecular coupling of amine tethered vinyl halides and ketone enolates in moderate yields . A palladium catalyzed decarboxylative carbonylation of 5-vinyl... 

In contrast to the high regioselectivity and good yields of electroreductive intramolecular coupling reactions of ketones with multiple bonds shown in Schemes 34 to 37, the yields of interm olecular coupling reactions have been very low until recently. However, by using carbon fiber electrodes, intermolecular coupling reactions have... 

Reductive cross-dimerization has been established with ketones and 0-meth-oximes upon reduction in isopropanol with a Sn cathode as a convenient route to yS-amino alcohols, diastereoselectivities of up to 85 15 were obtained. A chiral ligand was obtained this way from the coupling of (-) - menthone with O-methyl acetaldoxime. Similarly, ketones could be coupled to hydrazones and nitrones. Also, intramolecular couplings were achieved with good yields and diastereoselectivity (Fig. 56) [308]. 

Fig. 57 Stereoselective intramolecular coupling of ketones to cyclic diols [313, 310].

The McMurry coupling can be applied to intramolecular coupling of keto esters. Because the reactivity between ketone and ester groups is so different, the reaction usually requires individualized optimization, especially in the case of large rings. A combination of TiCls and LiAlH4 in the presence of triethylamine in DME is employed for the... 

Intermolecular reactions between 0-benzyl oximes and ketones (or aldehydes) are limited to those with formaldehyde O-benzyl oxime. However, intramolecular coupling proceeds with carbonyl-tethered oxime ethers (Equation (69)). 

In the related intramolecular version, an alkyne, Me2Zn and an a,/3-unsaturated ketone were coupled in the presence of a catalytic amount of №( ) and Me3SiCl to afford / -alkenylketones. The use of a chiral ligand such as 110 led to the development of an enantioselective version and ee s up to 81% could be obtained (equation 45)66. 

Cyclization of hydroxy acids 0-24 Cyclization of halo acids 0-89 Intramolecular coupling 2-43 Cleavage of cyclic a-cyano ketones 5-4 Internal addition of alcohols to a ke-tene function... 

It is reported that the palladium-catalysed intramolecular aromatization of 1,1 -dichloro-9/T-fluoren-9-yIidene (15) may lead to the formation of fullerene fragments.89 The amiulation reaction, under palladium catalysis, between iodoanflines and ketones may yield indole derivatives.90 There have also been studies of the palladium-catalysed carbonylation of o-iodophenols with allenes which may lead to l-benzopyran-4-one derivatives,91 of the intramolecular coupling of phenols with aryl halides,92 and of the intramolecular Heck aiylation of cyclic enamides.93... 

The intramolecular coupling of an aldehyde and alkene at —78 °C, promoted by Sml2, in the presence of a ketone, has led to a tandem coupling-addition process. This reaction has proved to be synthetically very useful for the preparation of poly-oxygenated compounds (equation 139)523. This reductive coupling process may also be promoted in dry methanol,... 

In 1986, Belotti, Pete and Portella reported that intramolecular ketone/olefin coupling could be achieved via photoinduced electron transfer (irradiation of an aliphatic ketone in HMPA)78. Several examples of this chemistry are highlighted below (Scheme 26). Intramolecular additions to C=C and allenes were also reported with yields in the range 70-80% however, additions to C=N were unsuccessful. 

Analogous intramolecular chelation-controlled ketone/olefin couplings with Sml2, in which Sm+3 was complexed in a cyclic manner to the ketyl anion and a /1-carbonyl of an ester or amide functionalilty, were reported as early as 1987 (Scheme 31)86. The cyclized samarium intermediate 49 could be further reacted with added electrophiles such... 

Sml2 -promoted, intramolecular ketone/alkyne couplings were reported in 1990 (equation 32)92. Yields were low (30-50%) for unactivated alkynes (Y = H or CH3), but improved to 50-75% when Y = Si(CH3)3, Ph or CC Et. Also, yields were typically much better for ketones than for aldehydes. 

One typical radical reaction is a coupling reaction. Oxidative decarboxylation coupling reaction of carboxylic acids by electrolysis (Kolbe electrolysis), intramolecular coupling reaction of diesters with Na (acyloin condensation), formation of pinacols from ketones or aldehydes with Na or Mg are well known classical methods [1,2]. Recently, oxidative... 

Irradiation of ketone (182) with a mercury lamp generates biradicals which are formed via n-TT electron transition. The reactive oxygen center of the biradical abstracts a hydrogen atom via 1,6-H shift, and the formed carbon-centered biradical couples intramolecularly to produce 5-membered compound (183) (eq. 3.70) Eq. 3.71 shows the same type of photochemical cyclization through the generation of a biradical, 1,9-H shift, and finally intramolecular coupling of the formed carbon-centered biradical [192-199]. 

Dimerization of ketone enolates. Frazier and Harlow1 have noted that ketone enolates (LDA or KH) couple to 1,4-diketones when oxidized by dry FeCl3 in DMF. Yields range from 25 to 70%. Paquette et al.2 have extended this reaction to intramolecular coupling of a bisenolate to a cyclopropane. Thus addition of a... 

The present radical formation was then applied to intramolecular cyclization. 3-Substituted cyclohexenone derivative 64 which has a (tributylstannyl)methylthio group in the side chain was irradiated (hv > 300 nm) in methanol. The desired spiro compound 65 was, however, obtained in low yield (23%) along with methyl sulfide 66 (60%) and dienone 67 (S%). In contrast, when 64 was irradiated in the presence of a 0.3 molar amount of 1,4-dicyanonaphthalene (DCN) as sensitizer in acetonitrile with 5 molar amounts of water, spiro ketone 65 was produced in 84% yield without a detectable amount of 66 and 67. Thus, by employing the DCN-mediated one-electron oxidation, the intramolecular coupling reaction proceeds smoothly (Scheme 27). 

Intramolecular coupling of carbonyl groups with vinylbromides after an addition-elimination sequence involves two electron-transfer steps. In the first step the ketone is reduced to the ketyl radical anion. After 5-exo-trig radical addition of the vinylbromide group, a primary radical is generated which is subsequently reduced to give an alkyl samarium species which eliminates bromide. This reaction... 

Exploration of the reduction of dicarbonyl compounds has centered on attempts to achieve intramolecular coupling of radical intermediates to give a cyclic 1,2-diol. A mechanistic study of the production of cyclopropanediols, during the reduction of 1,3-dibenzoylpropane in acetonitrile, has been made [110]. It is suggested that the ratedetermining cyclization step is the addition of the radical anion from one ketone function onto the second carbonyl group in the same molecule. 

The inter- and intramolecular coupling of two carbonyl groups of aldehydes or ketones in the presence of a low-valent titanium species produces a C-C bond with two adjacent stereocenters, a 1,2-diol (a pinacol). These may be further elaborated into ketones by the pinacol rearrangement or be deoxygenated to alkenes (McMurry reaction). 

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