Reductive coupling McMurry olefination

Reductive coupling of carbonyl compounds to yield olefins is achieved with titanium (0), which is freshly prepared by reduction of titanium(III) salts with LiAIH4 or with potassium. The removal of two carbonyl oxygen atoms is driven by T1O2 formation- Yields are often excellent even with sensitive or highly hindered olefins. (J.E. McMurry, 1974, 1976A,B). 

The synthetic method leading to Nb-alkylidenes and Nb-alkylidynes was particularly successful, due to a quite remarkable difference in the reaction rate of 29 with ketones or aldehydes, vs the subsequent reaction of the alkylidene with ketones and aldehydes (see Scheme 37). The former reaction takes a few minutes at -40°C, while the latter one occurs in hours at room temperature.88 The reaction between 178 and benzaldehyde led to triphenylethylene and the niobyl derivative 184. Due to the difference in reaction rates between a and b in Scheme 37, it was found that the sequential addition of two different ketones or aldehydes to a THF solution of 29 produced a nonsymmetric olefin in a stepwise McMurry-type reaction.84 This is exemplified in the coupling shown in reaction c (Scheme 37). The proposed reaction pathway does not involve the intermediacy of a pinacolato ligand and therefore differs from the mechanism of the McMurry reaction and related reductive couplings at activated metal sites.89... 

McMurry, J. E., and M. P. Fleming. 1974. A new method for the reductive coupling of carbonyls to olefins Synthesis of /3-carotene. J. American Chemical Society 96 4708-9. 

The twofold extrusion of nitrogen and sulfur and selenium and sulfur from 1-thia- and l-selena-3,4-diazolines(77), readily available from the reaction of diazoalkanes with thio- and selenaketones, respectively, as well as from the reductive coupling of carbonyl compounds such as 78, is the preferred method for preparation of olefins of type I and II (98,99). Examples of the extrusion method, developed by Barton (100), and the McMurry reaction (101) are given in Scheme 1. 

McMurry-Fleming olefin synthesis. Two laboratories ° have reported the synthesis of the crowded alkene tetraisopropylethylene by reductive coupling of 2,4-dimethyl-3-pentanone yields are 6% and 12%. The NMR indicates that the isopropyl groups of this alkene are not equivalent. 

A useful relative of the acyloin condensation is the McMurry olefination reaction. l in this reaction, ketones or aldehydes are treated with Ti(0) (TiCls + LiAlH4 TiCls + K TiCl3 + Li)2i5 to give alkenes.2 6 Reductive coupling is possible with a wide variety of ketones and aldehydes. i 3,217 Retinal (276), for example, was coupled with this reagent to give P-carotene (277) in 85% yield. ... 

McMurry olefin synthesis. Lenoir has published a variation of the McMurry reaction for reductive coupling of ketones (6, 589). The actual reagent presumably is also TiCl2, but is produced by reduction of TiCU in THF or dioxane with zinc. This reagent in the presence of pyridine converts ketones into tetrasubstituted alkenes. The reaction is most satisfactory with symmetrical ketones mixtures of (E)- and (Z)-isomers obtain from unsymmetrical ketones, with the latter predominating. Strongly hindered ketones are reduced by the reagent to the secondary alcohol. 

Reductive coupling of carbonyl compounds to olefins. Reductive coupling of carbonyls to olefins with a low-valent titanium reagent prepared from TiCla and LiAlHi (6, 589) tends to give erratic yields. McMurry and Fleming find that use of Ti(0) gives reproducible results. Yields are somewhat higher with metal prepared with potassium, but lithium is easier to handle. 1,2-Diols are also reduced to olefins. ... 

McMurry and Fleming have described the preparation of a slurry of active titanium powder, from TiCl3 and potassium metal in anhydrous THF under nitrogen, which can be used in the reduction of diols to give olefins and in the reductive coupling of alkanones to olefins. Thus, cyclohexanone gave an 85 % yield of (48) as also did... 

A titanium(Il) species formed from titanium trichloride and lithium aluminum hydride is a useful reagent for the reductive coupling of carbonyl compounds to olefins (McMurry, 1974 McMurry and Fleming, 1974). Both aliphatic and aromatic ketones can be converted to tetrasubstituted olefins in excellent yields. Reductive dimerization of retinal (CCLXXFV) affords j6-carotene (CCLXXV) in 85% yield. The course of the reaction can be accounted for by assuming pinacol formation followed by loss of titanium dioxide. 

Another well-known transformation of carbonyl derivatives is their conversion to pinacols (1,2-diols) via an initial one-electron reduction with highly active metals (such as sodium, magnesium, aluminum, samarium iodide, cerium(III)/ I2, yttrium, low-valent titanium reagents (McMurry coupling), etc.), amines, and electron-rich olefins and aromatics as one-electron donors (D).43 Ketyl formation is rapidly followed by dimerization44 (equation 22). 

The olefin metathesis of 3-hydroxy-4-vinyl-l,2,5-thiadiazole 112 and a McMurry coupling reaction (Ti3+ under reductive conditions) of the aldehyde 114 were both unsuccessful <2004TL5441>. An alternative approach via a Wittig reaction was successful. With the use of the mild heterogenous oxidant 4-acetylamino-2,2,6,6-tetramethyl-piperidine-l-oxoammonium perfluoroborate (Bobbitt s reagent), the alcohol 113 was converted into the aldehyde 114. The phosphonium salt 115 also obtained from the alcohol 113 was treated with the aldehyde 114 to give the symmetrical alkene 116 (Scheme 16) <2004TL5441>. 

In 1973 Mukaiyama, Tyrlik, and McMurry discovered a remarkably simple reaction that couples aldehydes or keto compounds reductively to olefins [1, 2]. This methodology following eq. (1) differs from that of Section 3.2.10 in that no extra methylene or alkylidene transfer reagent is required. The stereochemistry of the product depends on the nature of the substituents R and whether an open-chain or a cyclic olefin results. 

A titanium(O) colloid, prepared by the reduction of TiCU with KBEtsH, has been used in the synthesis of indoles [260]. Nanostructured titanium clusters, produced electrochemically by using a titanium sacrificial anode as the metal source and Bu4NBr in THF as the electrolyte and stabilizer, were found to induce olefin-forming McMurry-type coupling of oxoamides, aromatic aldehydes, and ketones [261]. 

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