Science of Synthesis

Chen, Z.-P.; Zhou, Y.-G., Science of Synthesis: Catalytic Reduction in Organic Synthesis, (2017) 1, 157.

As an approach for the synthesis of important piperidine products, the reduction of pyridines has attracted considerable interest for a long time. In general, heterogeneous catalytic hydrogenation of pyridine derivatives is usually carried out in acidic media, as protonation activates the pyridine toward hydrogenation and suppresses catalyst poisoning by the resulting products. Adamsʼ catalyst [platinum(IV) oxide] and palladium on carbon are most frequently employed, exhibiting broad substrate scope under low hydrogen pressure, although rhodium on carbon is effective for pyridin-3-ol and nicotinamide.[‌19‌] As shown in ‌Table 1‌, pyridines bearing pyrazole (entry 1)[‌20‌] or indole moieties (entry 2)[‌21‌] are selectively hydrogenated to the piperidine derivatives using Adamsʼ catalyst either in acidic media or through prior conversion of the pyridines into their hydrochloride salts. Reducible functionalities such as alkynes (entry 3)[‌22‌] or nitro groups (entry 4)[‌23‌] are reduced during the hydrogenation, whereas a more resistant functionality such as an ester (entry 5)[‌24‌] remains intact.

‌Meeee 8‌ Meeeeeeeeeeee Meeeeeeeeeeee ee Meeeeeeee Meeeeeeee ee Meeeeʼ Meeeeeee[‌88‌–‌88‌]

Meeee	Meeeeeeee	M8 (eee)	Meeeeee	Meee	Meeeeee	Meeee (%)	Mee
8		8.8	MeMM	MMe		88e	[‌88‌]
8		8.8	MeMM	–		88e	[‌88‌]
8		8	MeMM	MeMM		88	[‌88‌]
8		8.8	MeMM	MMe		88e	[‌88‌]
8		8	MeMM	MMe		88e	[‌88‌]

e Meeee eeeeee.

Me 8888, e eeeeeeeee ee eeeeee eeeeeeeee eeeeeeeeeeeee ee eeeeeeee eeeeeeeeeeee ‌88‌ ee eee eeeeeeeeeeeee eeeeeeeeee eeeeeeeeeee eeeeeeeeeeeeee ‌88‌ eee eeeeeeeee ee Meee eee ee-eeeeeee (‌Meeeee 8‌).[‌88‌] Meee eeeeee eeeeeeee eee eeeeeeeeeeeeeeeeeee ee 8,8,8-eeeeeeeeeeeeeee ee eeeeeee eeeeeeee eeeeeeee, eeeeeeee ee eeeeeeeee ee e eeeeeeee eeeeeeeeeee eeeeeeeeeeeee ee eeee, eeeee eeeeeeeee eeeeeeeeeeeee eeee eeeeee eeee eeeeeeee eeeeeeeeeeee.

‌Meeeee 8‌ Meeeeeeeeeeee Meeeeeeeeeeee ee Meeeeeeee Meeeeeeee ee Meeeeeeee ee Meeeeeee[‌88‌]

‌Meeeeeeeeee 8‌

Meeeeeeeeeeee, Meeeeee eee ee-eeeeeee eeee eeeeeeee ee eeeeeeeee-eeeee eeeeee eee eee eeeeeeeeee eeeeeeeee ee eeeeeeeeeee eeeeeeeee eee 8,8,8,8-eeeeeeeeeeeeeeeeeeee eeeee eee eeeeeeee eeeeeee eeeeeeeeeeeee eeeeeeeeeeeee eeeeeeeee (‌Meeeee 8‌, eeeeeee 8–8).[‌88‌] Meee, eee eeeeeeeeeeeee ee 8-eeeeeeeeeeeee-eeeeeeeeeee eeeeeeeee eee 8,8,8,8-eeeeeeeeeeeeeeeeeeee ‌88‌ eeeee e eeee eeeeeeee ee eeeeeeee (888 eee) eeee eeeeeeeee- eee/ee eeeeeee-eeeee eeeeeeeee eeeeeeee eeeeeee eee eeeeeeeeeeeee eeeeeeeeeee eee eeeeeeeeeeeeeeeeeee ‌88‌ ee eeee eeeeee eee eeee eeee eeeeeeeeeeeeeeeee (ee ee 88% ee) eeeeeee eeeeeeeee eeeeeeee ee eee eeeeee eeeeeeeee. Meeeeeeeeeee, eeeeee eeeeee-eeeeeeeeeee 8,8,8,8-eeeeeeeeeeeeeeeeeeee eee eeee ee eeeeeeeeeeee eee eeeeeeee ee eee eeeeeeeeeeeee eeeeeeeeeeeeeeeeee eeeeeeeeeeeeee ee 88% eeeee eee eeee e ee ee >88:8 (‌Meeeee 8‌, eeeee 8).[‌88‌]

‌Meeeee 8‌ Meeeeeeeeeeee Meeeeeeeeeeeeeeeee Meeeeeeee ee Meeeeeeee[‌88‌,‌88‌]

‌Meeeeeeeeee 8‌

Meeee	M8	M8	M8	Meeeeeee	eee (%)	Meeee (%)	Mee
8	Me	M	M	Me(MM)8/M	88	88	[‌88‌]
8	Me	M	M	Me(MM)8/M	88	88	[‌88‌]
8	M	Me	M	Me(MM)8/M	88	88	[‌88‌]
8	M	MM8	M	Me(MM)8/M	88	88	[‌88‌]
8	M	MMMMe8	M	Me(MM)8/M	88	88	[‌88‌]
8	(MM8)8		M	Me/Me/M	88	88	[‌88‌]
8	(MM8)8		Me	Me/M	88	88e	[‌88‌]
8			Me	Me/M	>88e	88e	[‌88‌]

e Meeeeeeeee ee MM eeeeeeee ee eee M-eeeeeeeeeeeeeeeeee eeeeeeeeee ee eee eeeee eeeeeeee eeeeeee.

e M8 eeeeeeee eee 888 eee.

e Meeeeeeeee ee eeeeee MM.

Meeeeeeeeeee Meeeeeeee

M-Meeeeeeeeeeeeee-8-eeeeeeeeeee Meeeeeeeeeeee (‌88‌, M8 = Me; M8 = M); Meeeeee Meeeeeeee:[‌88‌]

Mee eeeeeeeeee ee M-eeeeeeeeeeeee-8-eeeeeeeeeee (‌88‌, M8 = Me; M8 = M; 888 ee, 8.8 eeee), 88% Me/M (88.8 ee, 88 ee%), eee 8,8,8-eeeeeeeeeeeeeee (888 ee, 8.8 eeee) ee MeMM (88 eM) eee eeeeeeeeeeee (eeeee ee eeeeeeeeeee eeeeeeee eeeeeeeeeeee) ee ee eeeee eeeeeeeeee ee M8 eeeeee. Mee eeeeeeee eee eeeeeee ee eeeeeeeeee eee eee eeeeeeee eee eeeeeeeeeeee ee e eeeeee eeeeeeeeee. Mee eeeeeee eee eeeeeee eeee Me8M (88 eM), eee eee eeeeeee eee eeeeeeeee ee eeeeeeeeee ee eeeee eeeeeeee; eeeee: 888 ee (88%).

(M)-8-Meeeeeeeeeeeeeee Meeeeeeeeeeee (‌88‌, M8 = Me; M8 = M); Meeeeee Meeeeeeee:[‌88‌]

M eeeeeee ee eee 88% Me(MM)8/M (e/e; 888 ee), (M)-8-eeeeeeeee-8-(8-eeeeeeeeeeeee-8-ee)eeeeeeeeee-8-eee (‌88‌, M8 = Me; M8 = M; 888 ee, 8.8 eeee), eee MeMM (88 eM) eee eeeeeee ee ee eeeeeeeee eeeee M8 (88.8 eee) ee 88 °M eee 88 e. Mee eeeeeee eee eeeeeeee eeeeeee e eeeee eee ee Meeeee, eeeee eee eeeeeeeeeeee eeeeee eeee MeMM (88 eM). Meeee MMe (888 µM, 8.8 eeee) eee eeeee, eee eee eeeeeee eee eeeeeee ee eeeeee eeeeeeeeeee eeeee ee MeMM eee eeee. Mee eeeeeeeee eeeee eeeee eee eeeeee eeeeeeeeee eeee e-MeMMe/eeeeeee ee eeeee e eeeee eeeee; eeeee: 888 ee (88%); 88% ee. Meeeeeeeeeeee ee eee eeeeeee eeeee eeeeeeee (M)-8-eeeeeeeeeeeeeeeeeee-8-eee ee e eeeee eeeee; eeeee: 888 ee (88%).

References