Cleavage of methoxymethyl ethers with boron trichloride. A convenient, versatile preparation of chloromethyl ether derivatives

Abstract

vinyl ketone took place in this homogeneous system with no change in the optical yield. This modification, therefore, will allow the use of Michael acceptors that are not compatible with hydroxide bases.9 In summary, we have demonstrated a chiral catalytic process for the addition of MVK to indanone 1 which takes place in excellent chemical yield and up to 80% ee for the S enantiomer and 52% ee for the R enantiomer. Experimental SectionAssays for Optical Purity. Assays for optical purity were obtained by chiral liquid chromatography. A poor separation of the enantiomers 2 was obtained on a Pirkle covalent /-leucine column (Regis Chemical) with 0.75% isopropyl alcohol in hexane. However, base line resolution of the diastereomeric ketals formed from 2 and (2fi,3fi)-(-)-2,3-butanediol10 was obtained on a Pirkle ionic phenylglycine column with 88:12:0.5 hexane/chloroform/ isopropyl alcohol, flow rate of 2 mL/min, UV detector at 254 nm.Retention times S enantiomer, 5.8 min; R enantiomer, 6.2 min.Confirmation of the ee was obtained by NMR chiral shift studies on the enantiomeric mixture 2 with an equal weight (29 mol %) of tris[3-(heptafluoropropylhydroxymethylene)-d-camphoratojeuropium (III) derivative. The shift was observed in the methyl group adjacent to the carbonyl with the S enantiomer shifting to lower field relative to the R enantiomer.Catalysts. Catalysts 4 and 7 are commercially available from Chemical Dynamics Corporation, South Plainfield, NJ. Catalyst 5 was prepared from cinchonidine and 3,4-dichlorobenzyl chloride in refluxing THF. The reduced catalysts 6 and 8 were prepared by hydrogenation of 5 and 7, respectively, at 40 psi with 10% Pt/C in methanol. Catalyst 9 was prepared from 7 on an ion-exchange resin.Chiral Methyl Vinyl Ketone Additions. Preparation of 6,7-Dichloro-2,3-dihydro-5-methoxy-2-(3-oxobutyl)-2propyl-líf-inden-1-one. Three sets of conditions were employed for the Michael additions: (1) liquid/liquid phase-transfer conditions using toluene / 50% NaOH, (2) liquid/solid phase-transfer conditions using toluene/KOH pellets, and (3) homogeneous conditions using a solution of the preformed catalytic species.(13) This reaction should not be prolonged since decomposition of the catalyst does take place under these conditions.

Evaluation of an Intramolecular Approach for the Synthesis of the Elusive C58N2 Heterofullerene Family

“…As a result of the described synthetic problems and the absolute necessity of the azidomethoxy fragment in this project, alternative conditions for the chloromethylation reaction [step (ii)] had to be found. Whereas one possible strategy using MEM chloride and BCl 3 25 did not seem very practical, a procedure published by Shipov et al seemed very promising 26. It made use of paraformaldehyde instead of s ‐trioxane, and of TMS chloride instead of HCl gas.…”

Direct metalation of methoxymethyl arylmethyl ethers: A tin-free approach to the generation of α-alkoxyalkoxy-substituted aryllithiums

“…Arylmethyl methoxymethyl ethers were synthesized by the reaction of the corresponding arylmethyl alcohol with CH 3 OCH 2 Cl according to known procedures, either under basic (1a and 1c-l, NaH, THF) [19] or acidic (1b, Na-Y zeolite, CH 2 Cl 2 ) [20] reaction conditions.…”

“…Acetals 1a [19], 1b [20] and 1c-k [19] were synthesized according to general procedures, and purified either by fractional distillation or flash chromatography. Typical yields range from 70% to 85%.…”

H3PW12O40 — A selective, environmentally benign, and reusable catalyst for the preparation of methoxymethyl and ethoxymethyl ethers and their deprotections under mild conditions

“…These derivatives are frequently prepared by the reactions of alcohols with a excess amount of formaldehyde dimethyl acetal (FDMA) or formaldehyde diethyl acetal (FDEA) (18)(19)(20)(21)(22)(23)(24)(25). Deprotection of these ethers to their parent alcohols is also an important process in synthetic organic chemistry, and several methods and catalysts have been reported for these transformations (23,(26)(27)(28)(29)(30)(31)(32)(33). However, some of these methods suffer from drawbacks, such as harsh reaction conditions, high reaction temperature, tedious work-up procedures, long reaction times, and the use of expensive and toxic reagents.…”