Ketones McMurry coupling

A McMurry coupling of (176, X = O Y = /5H) provides ( )-9,ll-dehydroesterone methyl ether [1670-49-1] (177) in 56% yield. 9,11-Dehydroestrone methyl ether (177) can be converted to estrone methyl ether by stereoselective reduction of the C —double bond with triethyi silane in triduoroacetic acid. In turn, estrone methyl ether can be converted to estradiol methyl ether by sodium borohydride reduction of the C17 ketone (199,200). 

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... 

The intramolecular McMurry coupling between the C=0 group of an amide and the C=0 double bond of a ketone leads to the formation of a heterocycle with an enamine-like substructure. The most important heterocycle of this type is the indole skeleton ... 

Fig. 14.50. Crossed McMurry reactions ketone/ester coupling (top) and ketone/amide coupling (bottom).

McMurry coupling, Tebbe reagent, Petasis reagent and Takeda reagent) and catalytic alke-nation of aldehydes and ketones plus the related reactions in each case. 

Stuhr-Hansen has reported on a microwave-induced high yielding synthesis of alkenes by McMurry coupling of aldehydes and ketones. With microwave heating, the corresponding alkenes have been produced much faster with higher yields (>80%) as compared to conventional heating. 

The McMurry coupling is most useful for the intramolecular reduction of aldehydes and ketones to form cycloalkenes with ring size varying from 3 to 36. The medium and large rings are usually formed with the -configuration . 

A one-pot synthesis of phenanthrenes from ortho-alkoxy a re ne aldehydes and ketones has been accomplished using TiCl3-Li-THF [103]. The 2,2 dialkoxystil-benes, resulting from a classical McMurry coupling [80], are subjected to a reductive dealkoxylation and under the reaction conditions applied [103] form the intramolecular CC coupling products in moderate overall yields (25-38%). 

McMurry coupling of the appropriate ketones gave the alkenes which are converted into amines by treatment with dimethylamine at 60 °C. The McMurry coupling reaction gives a mixture of (Z) and ( )-isomers that can be separated by semipreparative HPLC. 

Alkenes can be obtained from aldehydes or ketones on reductive dimerization by treatment with a reagent prepared from titanium(III) chloride and zinc-copper couple (or L1A1H4), or with a species of active titanium metal formed by reduction of titanium(III) chloride with potassium or lithium metal. This McMurry coupling reaction is of wide application, but in intermolecular reactions generally affords a mixture of the E- and Z-alkenes (2.99). 

Furstner indole synthesis is not necessarily performed in a two-step fashion, instead it can be efficiently carried out via an instant method. Under such conditions, TiCb is added to form a complex with oxoamide substrates before the addition of an excess amount of zinc once TiCb is reduced to an active oxidation state, it immediately mediates the alkylidenation of two adjacent carbonyl functionalities. Furthermore, unlike McMurry Coupling, the Furstner indole synthesis is not restricted to THF or DME, it can also be performed in solvents such as EtOAc, DMF, and CH3CN, although it does not work in toluene and MeOH. What is more, a variety of reducible and acid or base-labile functionalities at other sites of the substrates can sustain the Eiirstner indole synthesis. Eor example, 2-N-o -ketoacylamidophenyl ketone with a more electrophilic a-keto group cyclizes only to a indole derivative. In addition, a pair of phenyl/mesityl or benzyl/t rt-butyl groups at C-2 and C-3 in either possible arrangement does not affect the overall yield of indole derivatives to a noticeable extent. ... 

McMurry coupling of aldehydes and ketones for the formation of heter-ocyles via olefination 12COC2097. 

A combination of alkali metal salts, particularly potassium chloride, with low-valent titanium reagents generated from titanium chlorides with lithium or magnesium in either THF or DME are effective reagents for stereoselective McMurry coupling reactions of aldehydes and ketones to substituted alkenes (Figure 1.11). 

Pinacolization sometimes occurs when undesired, but it is difficult or unsatisfactory when needed. A few attempts to improve this reaction by sonication (Fig. 18) have met with limited success, and a general solution to this problem remains to be found. Aromatic aldehydes and ketones pinacolize when sonicated with low-valent titanium in DME.57 The reaction is highly sensitive to the nature of the solvent. In apolar media, the reduction of titanium trichloride does not occur, and in THF, the McMurry coupling to olefinsHO is preferred. 

The initial idea in the preparation of complex 25 was to use tamoxifen as a vector for the potentially cytotoxic Cp2TiCl2 2 (section 2, this book). Preparation of complex 25, in which the aromatic p ring of tamoxifen is substituted by a Cp2TiCl2 entity, required development of a novel synthesis (Scheme 3.10) [72]. This synthesis starts with a McMurry coupling reaction between propionyl cyclopentadienyl manganese tricarbonyl 21 and the ketone 22, permitting preparation of the complex diphenyl-ethylene 23. This is converted to a cyclopentadienyl 24 via photochemical decomplexation, and immediately recomplexed in the presence of CpTiClj to give 25, which is isolated as the chloride. 

McMurry coupling of a,j5-unsaturated aldehydes and ketones constitutes an easy route to conjugated polyenes (Figure 6.2), which exhibit interesting electronic properties. After yS-carotene [3], a series of minicarotenes such as 11 has been syn-... 

Alkyl and acylsilanes Tetraalkylsilanes are inert to the carbonyl coupling reaction conditions, as shown by the syntheses of 43 and 44 [61, 62]. Despite their dose similarity to sterically hindered ketones, McMurry reactions of acylsilanes are limited to the preparation of the 1,2-disilylated stilbenes 45 (R = H, Br or OMe) silyl enol ethers are also obtained as by-products, resulting from silatropic migration [63], No such coupling of aliphatic acylsilanes has yet been reported. 

Scheme 6.8. Effect of pyridine on the McMurry coupling of a ferrocenyl ketone.

If both carbonyl substrates have sufficiently different redox potentials, a reasonable yield of crossed product is obtained without resorting to using one substrate in excess. This result was unexpected given the relative ease that a bisaromatic ketone should undergo ketyl formation followed by self pinacol coupling and was one of the first results that indicated more than one mechanism may be operative in McMurry couplings. In this case, the diaryl ketone may be reduced selectively to a dianion, which then undergoes nucleophilic addition to the saturated ketone. 

The McMurry reagent reductively couples trifluoroacetophenones to the eorresponding stilbenes [67] (equation 55), and cross-coupling of ketones is also reported [68] (equation 56). 

The intermolecular McMurry reaction is first of all a suitable method for the synthesis of symmetrical alkenes. With a mixture of carbonyl compounds as starting material, the yield is often poor. An exception to this being the coupling of diaryl ketones with other carbonyl compounds, where the mixed coupling product can be obtained in good yield. For example benzophenone and acetone (stoichiometric ratio 1 4) are coupled in 94% yield. ... 

The McMurry procedure is a valuable method for the synthesis of highly substituted, strained alkenes such compounds are difficult to prepare by other methods. Diisopropyl ketone 6 can be coupled to give tetraisopropylethene 7 in 87% yield attempts to prepare tetra-t-butylethene however were not successful. ... 

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