The Lewis Base-Catalyzed Silylation of Alcohols—A Mechanistic Analysis

Abstract

Reaction rates for the base-catalyzed silylation of primary, secondary, and tertiary alcohols depend strongly on the choice of solvent and catalyst. The reactions are significantly faster in Lewis basic solvents such as dimethylformamide (DMF) compared with those in chloroform or dichloromethane (DCM). In DMF as the solvent, the reaction half-lives for the conversion of structurally similar primary, secondary, and tertiary alcohols vary in the ratio 404345:20232:1. The effects of added Lewis base catalysts such as 4-N,N-dimethylaminopyridine (DMAP) or 4-pyrrolidinopyridine (PPY) are much larger in apolar solvents than in DMF. The presence of an auxiliary base such as triethylamine is required in order to drive the reaction to full conversion.

Leaving Group Effects on the Selectivity of the Silylation of Alcohols: The Reactivity–Selectivity Principle Revisited

“…The corresponding turnover curve is characterized by chemoselectivities C just below 1.0 for the first 50% turnover and a subsequent systematic decline to C = 0.0 afterward. The data points located in the critical region between 30 and 70% turnover can nicely be fitted with a selectivity value S = 120 obtained from previous direct kinetic measurements for alcohols 4a and 4b, 7 thus confirming the validity of the relative rate measurements obtained here. The same high selectivity S was measured under these conditions for silyl cyanide 1c, while that for silyl triflate 1b is much lower at S = 4.…”

“…13 These measurements were performed using the previously developed procedure for secondary alcohol 4b using 30 mol % of DMAP and Et 3 N (1.2 equiv) in CDCl 3 (Table 1). 7 Very little conversion can be observed under these basic conditions for silyl imidazole 1d, which is estimated to react 1 order of magnitude slower than 1e. For the more reactive reagents 1a, 1c, and 1e, the rate in DMF-d 7 is increased by 2 orders of magnitude compared to that in CDCl 3 , while for triflate 1b reaction rates are quite comparable in both solvents.…”

Amines vs. N‐Oxides as Organocatalysts for Acylation, Sulfonylation and Silylation of Alcohols: 1‐Methylimidazole N‐Oxide as an Efficient Catalyst for Silylation of Tertiary Alcohols

“…To the best of our knowledge, this is the first example of effective amine or N-oxide Lewis-base catalyzed silylation of tert-alcohols with a silyl chloride other than TMS-Cl [18] and provides an organocatalytic alternative to current methodology using mild reaction conditions and low catalyst loading whilst producing yields comparable to those previously reported. [43,44] In conclusion, we have directly compared a series of five commonly used Lewis-basic amines (1)(2)(3)(4)(5) and three N-oxides (6-8) as catalysts for the acylation, sulfonylation and silylation of primary, secondary and tertiary alcohol derivatives 9a-c. Whilst the amine catalysts are generally more efficient in the acylation processes, the N-oxides are generally more effective catalysts in the analogous sulfonylation and silylation reactions.…”

“…[45] As far as we are aware, no amine or N-oxide Lewis base has previously been reported to efficiently catalyse the formation of bulky silyl ethers from tert-alcohols (Scheme 2). [18] Scheme 2. Previous methods for silylation of tert-alcohols with TES-Cl or TBSCl.…”

“…[11][12][13] Although some comparative studies have been reported for specific reaction types, e.g. for acylation [14][15][16][17] and for silylation [18] to the best of our knowledge, a comparative study of the relative abilities of the most commonly used N-heterocycles to catalyse acylation, sulfonylation and silylation of alcohols has not been reported. We considered that comparative data of this type would be valuable to allow selection of the optimal Lewis base for a given transformation and might also provide insight into preferred structural features for particular types of transformations.…”