[1619-34-7]  · C7H13NO  · 3-Quinuclidinol  · (MW 127.21)

(cleavage of b-keto esters;1 catalyst for Baylis-Hillman reaction;2-6 synthesis of monoesters;7 oxygenation of branched aldehydes8)

Physical Data: mp 223-224 °C.

Solubility: sol water, ethanol, methanol.

Form Supplied in: crystalline solid; >98% purity.

Analysis of Reagent Purity: NMR, mp.

Preparative Methods: commercially available from several sources.

Purification: recrystallize from benzene or acetone.

Handling, Storage, and Precautions: corrosive.

Cleavage of b-Keto Esters.

3-Quinuclidinol selectively cleaves b-keto esters to ketones (eq 1).1 Typical reaction conditions involve heating the ester with a fivefold excess of quinuclidinol in o-xylene. The reaction is also successful for cleavage of vinylogous b-keto esters (eq 2).1

Baylis-Hillman Reaction.

3-Quinuclidinol is a much more efficient catalyst than 1,4-Diazabicyclo[2.2.2]octane (DABCO) for the Baylis-Hillman reaction, yielding 2-hydroxyalkenoate esters (eqs 3 and 4).2 Reaction times are much shorter, typically less than 24 h as compared to 4-7 days.3 The same results have been observed for the synthesis of hydroxy enones (eq 5).4 It has been speculated that the rate enhancement can be due to hydrogen-bonding stabilization of the catalyst-acrylate adduct5 by the hydroxyl group of quinuclidinol, which does not occur with DABCO. This methodology has also been extended to include the use of aromatic aldehydes (eq 6).6

Synthesis of Monoesters.

Geminal diesters are converted to the corresponding monoester with quinuclidinol (eq 7).7 Other bicyclic amines such as DABCO and 1,5-Diazabicyclo[4.3.0]non-5-ene (DBN) can also be used.7 These cleavage conditions are advantageous in that they involve a one-step process compared with two steps involving formation of the monoacid followed by esterification. More importantly, these reaction conditions are perfectly suited to cases where acid or base labile groups are present or where the compounds are not soluble in aqueous solutions.

Oxygenation of Branched Aldehydes to Ketones.

Copper-catalyzed oxygenation of a-branched aldehydes in weakly basic media yields ketones having one less carbon (eq 8).8 Van Rheenen found that the optimum reaction conditions use Copper(II) Acetate complexed with 2,2-bipyridyl or 1,10-phenanthroline as catalyst and bicyclic amines such as DABCO or 3-quinuclidinol in polar aprotic solvents rather than in alcohols.8

1. Parish, E. J.; Huang, B.-S.; Miles, D. H. SC 1975, 5, 341.
2. Drewes, S. E.; Freese, S. D.; Emslie, N. D.; Roos, G. H. P. SC 1988, 18, 1565.
3. Bode, M. L.; Kaye, P. T. TL 1991, 32, 5611.
4. Bailey, M.; Markó, I. E.; Ollis, W. D.; Rasmussen, P. R. TL 1990, 31, 4509.
5. Ameer, F.; Drewes, S. E.; Freese, S.; Kaye, P. T. SC 1988, 18, 495.
6. Drewes, S. E.; Emslie, N. D.; Khan, A. A.; Roos, G. H. P. SC 1989, 19, 959.
7. Miles, D. H.; Huang, B.-S.; JOC 1976, 41, 208.
8. Van Rheenen, V. TL 1969, 985.

Ellen M. Leahy

Affymax Research Institute, Palo Alto, CA, USA

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