Reductive Coupling of Terpenic Allylic Halides Catalyzed by Cp₂TiCl:  A Short and Efficient Asymmetric Synthesis of Onocerane Triterpenes

Abstract

[reaction: see text] Titanocene chloride catalyzes the regioselective alpha,alpha'-homocoupling of terpenic allylic halides. This process has been employed in the short and effective synthesis of terpenoids such as beta-onoceradiene (1), beta-onocerin (2), and squalene (3). Evidence is presented for eta1-allyltitanium species being involved in the coupling.

Ti/Pd Bimetallic Systems for the Efficient Allylation of Carbonyl Compounds and Homocoupling Reactions

“…[12b] 11; [22] 13-16; [45][46][47][48] 18; [49] 19; [50] 22; [51] 25; [52] 24, 26; [53] 27; [54] 30-33; [55][56][57] 36.…”

“…Other, more convenient, Würtz-type protocols have been developed that use different metals (such as Cu, [20] Sm, [21] Ti, [22] Fe [23] or Ni), [24] but, in all cases, allylic halides are required as starting materials. The use of allylic esters in Würtz-type reactions is rather unusual.…”

“…[30] This regioselectivity is in accordance with previously described results for the dimerisation of geranyl bromide and geranyl acetate. [22,25] It is worth noting that the E or Z stereochemistry of the double bond in the allylic substrate was mainly retained when ethyl carbonates of trisubstituted alkenes were used (Table 1, entries 1, 2 and 6). This stereospecificity in palladium-mediated coupling reactions of allylic carbonates is known [31] and suggests that the dimerisation process is faster than isomerisation of the h 3 -allylpalladium complex or the subsequent allyl radical.…”

“…This fact is remarkable when taken into account that homodimers are obtained in the titanoceneA C H T U N G T R E N N U N G (III)-mediated reactions of allylic halides, even in the presence of high amounts of water. [22] Formation of the a regioisomer as the major product is inconsistent with protonolysis of the allyltitanium(IV) complex, which would take place preferentially at the g-position.…”

Role of cluster size and substrate in the gas phase CC bond coupling reactions of allyl halides mediated by Agn+ and Agn−1H+ cluster cations

“…One of the most widely studied classes of C C bond coupling reactions are metal mediated reductive coupling of organohalides, the so called "Wurtz" reaction [7]. For example, reductive coupling of allylhalides has been examined with a range of metal species [8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23] including gas phase iron cations [24] and metal surfaces [25][26][27]. Both silver surfaces [28,29] and silver nano-particles [30] are effective at mediating carbon carbon bond coupling of allyl halides to give 1,5-hexadiene.…”