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Synthesis of Tetrahydro-2-(2-propynyloxy)-2H-pyran: Illustrating Markownikov Addition, Protecting Groups, and Advanced ^sup 1^H-NMR Phenomena
To illustrate the anti-Markownikov regiochemistry of hydroboration-oxidation conditions (1), we have been using an excellent microscale procedure that appeared in this Journal (2). Almost all introductory organic chemistry text books juxtapose hydroboration-oxidation with oxymercuration-demercuration to present key mechanistic and synthetic aspects involved in alkene hydration, but few introductory organic laboratory texts use oxymercurationdemercuration to illustrate Markownikov regiochemistry (3). We desired to pair the hydroboration-oxidation lab with an exercise that would accomplish more than simply yield an alcohol having opposite regiochemistry, so we shifted our attention away from oxymercuration-demercuration and focused on the preparation of tetrahydro-2-(2-propynyloxy)2H-pyran (3) as a complement to hydroboration-oxidation.
Using the method of Grieco and coworkers (4) (eq 1), 3 can be synthesized, purified (via flash column chromatography [5]), and characterized in one 3.5-hour lab period. The starting materials are readily available and inexpensive, and a variety of concepts and phenomena can be introduced in the course of the exercise. The PPTS functions as a true catalyst in activating the enol ether moiety of dihydropyran (2) toward nucleophilic addition by propargyl alcohol (1). The final product (3) is an acetal-an extremely important functionality, particularly in natural product and carbohydrate chemistry. Formation of a THP-ether leads directly into a discussion of functional group protectiondeprotection (6) and serves as a conceptual connection to the rapidly developing field of combinatorial chemistry (7) when compared to a solid-phase resin recently designed by Thompson and Ellman (8) (eq 2). Characterization by 1HNMR illustrates (i) spin-spin coupling between diastereotopic protons and (ii) long-range (i.e., four-bond) coupling from an acetylenic proton to a propargylic position.
Experimental Procedure
To an oven-dried 25-mL round-bottomed flask, add a stir bar, 30 mg of PPTS [NOTE: hygroscopic! Weigh it out quickly and cap the bottle tightly when finished], and cap with a rubber septum. Flush the reaction flask head space with ca....