Determination of the pK_aof Cyclobutanone: Brønsted Correlation of the General Base-Catalyzed Enolization in Aqueous Solution and the Effect of Ring Strain

Abstract

The induction of strain in carbocycles, thereby increasing the amount of s-character in the C−H bonds and the acidity of these protons, has been probed with regard to its effect on the rate constants for the enolization of cyclobutanone. The second-order rate constants for the general base-catalyzed enolization of cyclobutanone have been determined for a series of 3-substituted quinuclidine buffers in D2O at 25 °C, I = 1.0 M (KCl). The rate constants for enolization were determined by following the extent of deuterium incorporation (up to ∼30% of the first α-proton) into the α-position, as a function of time. The observed pseudo-first-order rate constants correlated to the [basic form] of the buffer and yielded the second-order rate constants for the general base-catalyzed enolization of cyclobutanone for four tertiary amine buffers. A Brønsted β-value of 0.59 was determined from the second-order rate constants determined. Comparison of the results for cyclobutanone to those previously reported for acetone and a 1-phenylacetone derivative, under similar conditions, indicated that the ring strain of the carbocycle appeared to have only a small effect on the general base-catalyzed rate constants for enolization. The similarity of the rate constants for the general base-catalyzed enolization of cyclobutanone to those determined for acetone allowed for an estimation of the limits of the rate constant for protonation of the enolate intermediate of cyclobutanone by the conjugate acid of 3-quinuclidinone (k BH = 5 × 108 − 2 × 109 M−1 s−1). Combining the rate constants for deprotonation of cyclobutanone (k B) and protonation of the enolate of cyclobutanone (k BH) by 3-quinuclidinone and its conjugate acid, the pK a of the α-protons of cyclobutanone has been estimated to be pK a = 19.7−20.2.

Stereoselective Synthesis of trans-Decalin-Based Spirocarbocycles via Photocyclization of 1,2-Diketones

“…(S)-8a-Methyl-3,4,8,8a-tetrahydro-2H-spiro[naphthalene-1,2′- [1,3] General Procedure A: Enantioselective Synthesis of 1,2-Diketones. To a solution of liquid ammonia (200 mL) was added lithium solid (683 mg, 97.62 mmol, 3.5 equiv) at −78 °C in a portionwise manner over 5 min.…”

“…Synthesis of (4aS,5S,8aS)-5-(But-2-yn-1-yl)-8a-methylhexahydro-2H-spiro[naphthalene-1,2′- [1,3]dioxolan]-6(5H)-one (3). Yellowish oil, 4.62 g (16.82 mmol), 60%, R f = 0.31 (silica gel, hexane/EtOAc = 5:1, KMnO 4 ); [α] D 25 = 2.69 (c = 1.0, in CHCl 3 ); IR ν max 2950,1710,1448,1185,1107,1067,949, 920 cm −1 ; 1 H NMR (500 MHz, CDCl 3 ) δ 4.00 4H),1H),3H),1H),2.03 (td,J = 12.3,3.3 Hz,1H),1H),7H),2H),1H), 1.22 (s, 3H); 13 C NMR (125 MHz, CDCl 3 ) δ 210.…”

“…In this aspect, α-hydroxyl cyclobutanone derivatives are particularly attractive because of their usefulness as starting materials for the preparation of structurally diverse molecules . Because of its high ring strain, synthesis of cyclobutanone is challenging. Although there are various ways to prepare α-hydroxyl cyclobutanone derivatives, the Norrish–Yang reactions of alkyl α-diketones turns out to be one of the most effective methods of choice .…”

Synthesis of Fulvene Vinyl Ethers by Gold Catalysis

“…Hence, the yield could not be determined. Cyclic ketonesr eactedw ell, except cyclobutanone (entry 2), possibly due to the build-up of ring strain upon forming ac yclobutenol moiety, [29] inhibiting the deprotonation of the oxo-nium intermediate. In case of unsymmetric ketones, the formation of the vinyloxy group obeys Hofmann's rule, giving the kinetic product 3v (entry 6).…”

Stereocontrolled Synthesis and Functionalization of Cyclobutanes and Cyclobutanones

“…Among the different transformations of the cyclobutane system, the α-functionalization in most cases [44] involves the use of organometallic-based reactions or metal catalyzed transformations [45,46,47,48].…”