Titanium-induced intramolecular coupling

In 1977, McMurry and Kees [152] developed a titanium-induced intramolecular coupling procedure to form cycloalkenes from dicarbonyl compounds. Mechanistically, as shown in Scheme 85, the coupling reaction proceeds by an initial pinacol dimerization of the dicarbonyl 253 to 254, followed by titanium-induced deoxygenation to afford alkene 255. 

Macrocyclization has been achieved through the formation of C=C as a key step using various reactions such as intramolecular Wittig-like reactions [46], titanium-induced intramolecular coupling method [65], and ring-closing metathesis (RCM) reaction developed by Grubbs [66, 67] (Scheme 6.6). 

The first total synthesis of ( )-sarcophytol B (5) from S./i-famesal (92), which was reported by McMurry et al. in 1989, used a low-temperature titanium-induced pinacol coupling reaction of 1,14-dialdehyde as the key step. They concluded that the natural sarcophytol B has the stereochemistry of a trans diol (Scheme 6-5). Li et al. reported on a concise total synthesis of ( )-sarcophytol B (5) from /i./i-famesol (91) by a low-valent titanium-mediated intramolecular McMurry... 

Yue et al. reported on the total synthesis of / -(—)-cembrene A by using the mod-ihed Wittig reaction and titanium-induced intramolecular carbonyl coupling as key steps the overall yield is 29% starting from -geranylacetone (164) and R-(+)-limonene (168) (Scheme 6-15). ... 

An alternative strategy to prepare ( )-cembrene A (59) by this group is described below. The key step here is a titanium-induced intramolecular carbonyl coupling reaction starting from -geranylacetone and geraniol (137) (Scheme 6-16). ... 

Titanium-induced Intramolecular Carbonyl Coupling Reactions... 

Table 9-1 Effect of the ring size on intramolecular, low-valent titanium-induced carbonyl coupling reactions.

This reaction was first reported by Furstner in 1991It is a low-valent titanium-induced or -mediated intramolecular reductive alkylidenation of alkyl (or aryl) 2-N-acylamidophenyl ketones to afford 2,3-disubstituted indoles, also known as titanium-induced intramolecular oxoamide coupling or the zipper reaction. Therefore, this reaction is referred to as the Furstner indole synthesis. 

Titanium (iv) chloride with zinc in pyridine has been found to couple ketones reductively to afford symmetrical tetrasubstituted ethenes. Unsymmetrical alkenes can be synthesized in useful yields by titanium-induced ketone coupling if the less reactive component is used in excess. Cycloalkenes (ring size 4—16) are prepared in good yield by intramolecular coupling of the corresponding alkanedione. ... 

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