Alkenes McMurry coupling

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>. 

Macrolactone synthesis 6,51, 71, 72, 94, 124,131,163,187,195 McMurry coupling 43 Medium ring synthesis 43,45,75, 77 Metathesis, Alkene (see Grubbs) Metathesis, Alkyne (see alkyne metathesis) Michael addition Intramolecular 166,166, 167,201 Intermolecular 57,84, 153, 166,204... 

Fig. 17.55. Reductive coupling of a dicarbonyl compound to afford diastereomeric glycols or diastereomeric alkenes (McMurry reaction).

A prototype example is the famous McMurry coupling of carbonyl compounds to alkenes (Scheme 1) [4]. The very high stability of the accumulating titanium oxides constitutes the thermodynamic sink which drives the conversion but demands the use of stoichiometric or excess amounts of the low-valent titanium reagent [Ti]. Only recently has it been possible to elaborate a procedure that for the first time enables us to perform intramolecular carbonyl coupling reactions catalyzed by titanium species [5]. 

Scheme I. The McMurry coupling of carbonyl compounds to alkenes.

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 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). 

The mechanism of the McMurry coupling is not entirely clear, but it is composed of two distinct steps 1) pinacol formation and 2) deox genation to the alkene. Extensive research showed that the low-valent titanium is most likely a mixture of Ti " and Ti ° , and the ratio of these species depends on the method of preparation (solvent, temperature, reducing agent, J ecent findings suggest that the reaction possibly involves the formation of a carbene or a metal carbenoid. The nature of the intermediates is strongly dependent on the structure of the carbonyl substrate and the reaction conditions, which is why the reaction is tricky and yields are difficult to reproduce in the laboratory. 

Table 2 Preparation of Sterically Hindered Alkenes by the McMurry Coupling Reaction...

The reductive coupling of two carbonyl compounds using reduced Ti reagents is called McMurry coupling. The products may be 1,2-diols or alkenes. 

McMurry couplings. Both alkenes and v/c-diols are prepared from carbonyl... 

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. 

This is called a McMurry coupling - use the correct name. Elimination of the bromide could result in an alkene as a competitive side reaction. 

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). 

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). 

The McMurry coupling reaction generally leads to three alkenes, two symmetrical products and one asymmetrical. However, depending on the reaction conditions, especially changes in temperature and medium, other secondary compounds are also formed, in particular, the transposition product and pinacol [129]. These two new species were synthesized and studied by orienting the reaction more specifically in their favor. The IC50 values of these compounds are collected in Table 42.7. 

Phospholes The only example of McMurry coupling of a carbonyl substrate bearing a phosphorus functional group is provided by the synthesis of the 1,2-bis(2-phospholyl)alkenes 42 (R = Me, Ph) [60] (Figure 6.8). 

Alkenes may be generated via the intra- or intermolecular reductive coupling of carbonyl compounds in a titanium-mediated process known as the McMurry coupling. ... 

In addition to the numerous examples of the McMurry couplings described above, the following examples illustrate the power of the transformation in the synthesis of a broad range of natural products and non-natural molecules. Of particular note in the following examples is the impressive functional group tolerance of the McMurry conditions. In general, alcohols, tosyl alcohols, alkyl ethers, silyl ethers, alkyl silanes, vinyl silanes, amines, sulfides, and alkenes are inert to McMurry conditions. Acteals, halides, alkynes, nitriles, and carboxylic acids are semi-compatible. 

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