Titanium-induced intramolecular

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. 

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... 

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. 

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... 

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

Lewis acid mediated intramolecular C-C bond formations represent another major class of reactions adaptable to seven-membered ring synthesis. A superb example of this class is found in the work of Majetich, which features a titanium-induced cyclization reaction employed in the synthesis of several natural products, including bar-batusol (Eq. 4)7 Although technically this closure has a nucleophilic... 

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. ... 

Although terminal acetylenes themselves do not form stable titanium—acetylene complexes upon reaction with 1, the reaction with terminal alkynes having a keto group at the 5- or y-position induces an intramolecular cyclization, apparently via the above titanium-acetylene complex to afford the four- and five-membered cycloalkanols, as shown in Eq. 9.6 [28]. 

The facile generation of this species involves transfer of a methyl group from silicon to boron and O—Si bond formation in the coordination sphere of the titanium atom and is due to the fact that the Si— CH3 bond is comparatively reactive and easily accessible. Attack of the Lewis base THF at the most Lewis acidic center of this compound (the Ti atom) induces an intramolecular nucleophilic attack of the CH2SiMe3 group on the oxygen-bound Si atom, which... 

When Pschorr reported more than a century ago on the first intramolecular homolytic aromatic substitution [25], he showed that biaryls could be readily prepared by intramolecular homolytic aromatic substitution using reactive aryl radicals and arenes as radical acceptors. The aryl radicals were generated by treatment of arene-diazonium salts with copper(l) ions. Today, this reaction and related processes are referred to as Pschorr reactions. It was later found that radical biaryl synthesis could be conducted without copper salts by photochemical or thermal generation of the aryl radical from the corresponding diazonium salt [26], Moreover, the reduction of aryl diazonium salts offers another route to generate reactive aryl radicals. Hence, electrochemistry [27], titanium(lll) ions [28], Fe(II)-salts [29], tet-rathiafulvalene [30] and iodide [31] have each been used successfully for the reduction of diazonium salts to generate the corresponding aryl radicals [32]. As an example, the iodide-induced cycUzation of diazonium salt 6 to phenanthrene derivative 7 is presented in Scheme 13.3 [31]. For further information on the... 

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