Science of Synthesis

Adolfsson, H., Science of Synthesis, (2008) 37, 234.

As stated in Section ‌37.2.1.1.1.2‌, the use of early transition-metal complexes in combination with aqueous hydrogen peroxide as the terminal oxidant is often problematic due to the inherent oxophilicity of such metals. However, Katsuki has reported a significant breakthrough in the field of titanium-catalyzed asymmetric epoxidation of non-functionalized alkenes.[‌28‌–‌30‌] The successful catalysts used in this system are based on a combination of titanium and reduced salen-type ligands (also known as salenan and salan, respectively). The oxidation of terminal alkenes, such as vinylbenzene and oct-1-ene, using catalyst ‌3‌ results in good yields (90 and 70%, respectively) and excellent stereocontrol (93 and 87% ee, respectively) of the formed epoxides (‌Scheme 6‌). Most strikingly, only 1 mol% of the catalyst and 1.05 equivalents of 30% aqueous hydrogen peroxide are required in the epoxidations. When this catalytic system is employed for the epoxidation of 1,2-dihydronaphthalene, the corresponding epoxide is obtained in 99% yield and 99% ee. The dimeric μ-oxo bridged catalyst ‌3‌ with its half-reduced salen ligands has a rather elaborate structure and a somewhat complicated preparation procedure. Nevertheless, its stability is remarkable because the homochiral complex keeps its dimeric structure in methanol for more than 24 hours. For a comparison, the corresponding salen-type complex, which is completely inactive as an epoxidation catalyst under these conditions, dissociates immediately into monomeric titanium–salen species in methanol. The difference in catalytic activity observed between catalyst ‌3‌ and the corresponding titanium–salen complex is believed to be due to the presence of intramolecular hydrogen bonding between the amine N—H bond and a peroxo group on the metal, which activates the complex for the oxygen transfer to the substrate. A synthetically less challenging and more flexible analogue of catalyst ‌3‌ has also been evaluated as an epoxidation catalyst in the presence of aqueous hydrogen peroxide. Complex ‌4‌ (Ar1 = Ph) can be easily prepared directly from titanium(IV) isopropoxide and the salan ligand; it is, however, less active and selective than catalyst ‌3‌. A structural modification of the initial salan ligand used in the study, however, has led to the development of catalysts that are able to form epoxides with a high degree of stereocontrol. As shown in ‌Scheme 7‌, catalysts based on complex ‌4‌ (Ar1 = 2-MeOC6H4) and ‌4‌ (Ar1 = 2-F3CC6H4) are able to epoxidize a range of alkenes in good yields and with excellent selectivity. As in the case of the corresponding manganese–salen systems, Z-substituted alkenes are the preferred substrates. The epoxidation reaction is reported to be stereospecific because no trans-epoxides are formed when starting from Z-alkenes.

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‌Meeeee 8‌ Meeeeeeeee Meeeeeee-Meeeeeeee Meeeeeeeeee[‌88‌–‌88‌]

‌Meeeeeeeeee 8‌

M8	M8	Meeeeeee	Meeeeeeeee	ee (%)	Meeee (%)	Mee
Me	M	8	8 eee% eeeeeeee, MM8Me8, 88 e	88	88	[‌88‌]
		‌8‌ (Me8 = Me)	8 eee% eeeeeeee, 88 e	88	88	[‌88‌]
		‌8‌ (Me8 = 8-MeMM8M8)e	8 e	88	88	[‌88‌]
		‌8‌ (Me8 = 8-M8MM8M8)e	8 e	88	88	[‌88‌]
		8	8 eee% eeeeeeee, MeMMe, 88 e	88	88	[‌88‌]
		‌8‌ (Me8 = Me)	8 eee% eeeeeeee, 88 e	88	88	[‌88‌]
		‌8‌ (Me8 = 8-MeMM8M8)e	8 e	88	88	[‌88‌]
		‌8‌ (Me8 = 8-M8MM8M8)e	8 e	88	88	[‌88‌]
M≡MMe	Me	8	8 eee% eeeeeeee, MeMMe, 88 e	88	88	[‌88‌]
		‌8‌ (Me8 = Me)	8 eee% eeeeeeee, 88 e	88	88	[‌88‌]
		‌8‌ (Me8 = 8-MeMM8M8)e	8 e	88	88	[‌88‌]
		‌8‌ (Me8 = 8-M8MM8M8)e	8 e	88	88	[‌88‌]
(MM8)8Me	M	8	8 eee% eeeeeeee, MM8Me8, 88 e	88	88	[‌88‌]
		‌8‌ (Me8 = Me)	8 eee% eeeeeeee, 88 e	88	88	[‌88‌]

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Meeeeeeeee Meeeeeee ‌8‌; Meeeeee Meeeeeeee Meeee Meeeeeee ‌8‌:[‌88‌]

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References