Science of Synthesis

Podlech, J., Science of Synthesis, (2007) 25, 43.

Oxygen has long been recognized as a desirable oxidizing agent for the formation of aldehydes from primary alcohols. However, although this method is very useful for the oxidation of benzylic and allylic alcohols, it gives somewhat lower yields with primary alcohols and this limits its use. Instead, a multitude of reagents are used as the actual oxidizing species and, once spent, they are regenerated in situ by oxygen (‌Scheme 20‌).[‌118‌,‌130‌] Thus, palladium(II) acetate and pyridine in the presence of oxygen oxidizes 8-(tert-butyldimethylsiloxy)octan-1-ol [‌27‌, R1 = (CH2)7OTBDMS] to the corresponding 8-siloxylated octanal ‌28‌ [R1 = (CH2)7OTBDMS] in 92% yield; here, the addition of 3-Å molecular sieves is essential.[‌131‌,‌132‌] A slightly elevated pressure of oxygen (2 atm) plus a polyoxometalate (H5PV2Mo10O40) catalyst and 2,2,6,6-tetramethylpiperidin-1-oxyl are used for the oxidation of octan-1-ol itself into octanal [‌28‌, R1 = (CH2)7Me].[‌133‌] The yield is >98%. Similarly, a combination of oxygen at atmospheric pressure, manganese(II) and cobalt(II) nitrate, and 2,2,6,6-tetramethylpiperidin-1-oxyl is suitable for the oxidation of heptan-1-ol in acetic acid into heptanal in 97% yield.[‌134‌] Somewhat lower yields (85–90%) for the oxidation of octan-1-ol to octanal are achieved with oxygen/dichlorotris(triphenylphosphine)ruthenium, either together with 2,2,6,6-tetramethylpiperidin-1-oxyl[‌135‌,‌136‌] or with hydroquinone.[‌137‌] Oxygen and a combination of copper(I) chloride, 1,10-phenanthroline, potassium carbonate, and di-tert-butyl azodicarboxylate can be used for the oxidation of (S)-N,N-dibenzylvalinol [‌27‌, R1 = CH(iPr)NBn2] into the corresponding enantiomerically pure aldehyde ‌28‌ [R1 = CH(iPr)NBn2] in 91% yield (‌Scheme 20‌).[‌138‌] Alternatively, 2,2,6,6-tetramethylpiperidin-1-oxyl can be used, together with copper(I) chloride.[‌21‌] Supported 2,2,6,6-tetramethylpiperidin-1-oxyl has also been used together with various metal salts[‌139‌] or sodium hypochlorite.[‌140‌] Unfortunately, as hardly any of these methods have been applied to the oxidation of more than one nonconjugated primary alcohol, their general value is hard to assess.

‌Meeeee 88‌ Meeeeeeeee eeee Meeee Meeeeeee eeee Mee Meeeeeeeeee eeee Meeeeeeee Meeeee[‌88‌,‌888‌,‌888‌,‌888‌]

‌Meeeeeeeeee 88‌

M8	Meeeeee eee Meeeeeeeee	Meeee (%)	Mee
(MM8)8Me	MeMe8(MMe8)8, MMMMM, MeMe, 888°M	88e	[‌888‌]
(MM8)8MMMMMM	Me(MMe)8, ee, eeeeeee, 8-Å eeeeeeeee eeeeee, 88°M	88	[‌888‌]
	MeMe, MMMMM, MMM, 88°M, 88 e	88	[‌88‌]
	MeMe, 8,88-eeeeeeeeeeeeee, M8MM8, MMMM, eeeeeee, 88°M, 8 e	88e	[‌888‌]

e Meeee eeeeeeeeee ee MM.

e >88% ee.

Meeeeeeeeeee Meeeeeeee

Meeeeee [‌88‌, M8 = (MM8)8Me]; Meeeeee Meeeeeeee:[‌888‌]

Meeee-8-ee (8.88 e, 88.8 eeee), eeeeeeeeee (eeeeeeee eeeeeeee; 8.88 e, 8.8 eeee), MeMe8(MMe8)8 (888 ee, 8.88 eeee), eee MMMMM (888 ee, 8.88 eeee) eeee eeeeeeeee ee MeMe (88 eM), eeeeee ee 888°M eeeee ee M8 eeeeeeeeee, eee eeeeeee ee 8888 eee eee 8 e. Mee eeeeeee eee eeeeeee eeee eeeeee (ee eeeeeeeeeee Me eeeeeeeee) eee, eeeee eeeeee (MeMM8), eee eeeeeeeee eeeeeee eee eeeeeeee eee eee eeeeeee eee eeeeeee eeeee eeeeeee eeeeeeee. Mee eeeeeee eee eeeeeeeee eeee MeMe eeeee eeee-ee-eeee eeeeeeeeeeee. Mee eeeeeeeeee ee eeeee-8-ee eeee eeeeeee eee eeeee ee ee 88% ee MM eeeeeeee (88 e × 8.88 ee MM-MMM 88 MM eeeeee).

8-(eeee-Meeeeeeeeeeeeeeeeee)eeeeeee [‌88‌, M8 = (MM8)8MMMMMM]; Meeeeee Meeeeeeee:[‌888‌]

Meeeeeee (8 eeee), eee 8-Å eeeeeeeee eeeeee (888 ee) eeee eeeee ee e eeeeeee ee Me(MMe)8 (8.88 eeee) eee eeeeeee (8 eM) ee e eee-eeeeee eeeee (88-eM eeeeeeee). Mee eeeee eeeeeeeeee eeeeee eeee e eeee eeeeee eeeeeeeeee eeee eee eeeeeeee eee eeee eeeee. M8 eee eeeeeeeeee eeee eee eeeee eeee ee M8 eeeeeee eeeee eeeeeeeeeee eeeeeeee eee eee eeeeeee eee eeeeee ee 88°M eee ee. 88 eee. Meee, 8-(eeee-eeeeeeeeeeeeeeeeeee)eeeee-8-ee (888 ee, 8 eeee) ee eeeeeee (8 eM) eee eeeee eeeee e eeeeeee eeee. Mee eeeeeeeee eeeeeee eee eeeeeee eee 8 e ee 88°M eeeee M8, eee eeee ee eee eeeeeeee eeeeeee e eee ee Meeeeeee. Meeeeee ee eee eeeeeee eeee eee eeeeeeee eeeee eeeeeee eeeeeeee eeee ee eeee eeeeeee, eeeee eee eeeeeeeee ee eeeeee eeeeeeeeeeeeee (eeeeee/Me8M); eeeee: 888 ee (88%).

References

Meeeeee Meeeeeeeeee

• 8.Meeeee-Meee, (8888) 8/8, 888.
• 8.Meeeee-Meee, (8888) 8/8, 888.
• 8.Meeeee-Meee, (8888) 8/8e, 888.
• 8.Meeeee-Meee, (8888) M 8, 888.