[116-11-0] · C4H8O · 2-Methoxypropene · (MW 72.12)
(electron-rich alkene used in the monoprotection of aliphatic,2 allylic,3 and propargylic4 alcohols, often followed by Claisen3b -e or other2a,4c rearrangements; protection of peroxides,5 cyanohydrins,6 a-hydroxy ketones,2b and phenols;7 condensation with amines;8 protection of 1,2-9,10 and 1,3-diols,10,11 sometimes followed by Prins9f,g rearrangements; protection of 1,2-dithiols10a and a-hydroxy carbamates;12 participant in pericyclic reactions;13 formation of 2-methoxyallyl halides14 and substituted furans4b)
Alternate Names: 2-MP; isopropenyl methyl ether.
Physical Data: bp 34-36 °C; n
Form Supplied in: colorless liquid; commercially available.
Preparative Method: prepared in high yield from Succinic Anhydride, 2,2-Dimethoxypropane, benzoic acid, and Pyridine.15
Handling, Storage, and Precautions: flammable liquid; light-sensitive; should be refrigerated.
2-Methoxypropene is used as a protective group for aliphatic,2,11d allylic,3 and propargylic4 alcohols, masking them as their mixed acetals (eq 1). Deprotection can be accomplished by stirring in MeOH over ion exchange resin,4a by reaction in methanol with catalytic Acetyl Chloride,11d by Potassium Carbonate in methanol,2c or by 20% Acetic Acid.3a A general advantage of this acetal, which undergoes hydrolysis at approximately 103 times the rate of THP,2d,3a is that it does not confer an additional diastereomeric center to the protected substrate. Access to allyl vinyl ethers for subsequent Claisen rearrangements3b-e is illustrated in eq 2.
A useful entry into b-keto allenes is provided by the reaction of 2-MP with tertiary propargylic alcohols.4c Base-catalyzed rearrangement of the allenes affords conjugated dienones (eq 3).
Stable allylic peroxyacetals have been prepared by reacting 2-MP with hydroperoxides (eq 4).5 Organomercury functionality is tolerated in this reaction.5b Cyanohydrins,6 a-hydroxy ketones,2b and phenols7 are similarly protected.
Imine formation with loss of methanol occurs under acidic conditions, as illustrated in eq 5.8
When another hydroxy group is in close proximity to the initially protected alcohol functionality, acetonide formation occurs.9-11 The kinetic product is preferentially formed.10b,c,11c As anomeric hydroxy groups do not usually11 participate, this reagent provides complementary selectivity to the more traditional acid/acetone acetonation protocol. Control of the amount of 2-MP can result in varying degrees of protection (eq 6).10b
Acetonide formation using n-Butyltrichlorostannane with 2-MP10a is quite general for 1,2- and 1,3-diols, as well as for 1,3-dithiols. Monoacetonide formation occurs with 1,2,3- and 1,2,4-triols. Yields of the acetonides (e.g. 1-5) show improvement over conventional procedures.10a
Aminal formation from a-hydroxy carbamates also occurs using 2-MP, as illustrated in eq 7.12
2-MP is an active participant in pericyclic reactions. A few examples include a substitution-dependent ene reaction with an alkynyl Fischer carbene complex (eq 8),13c a [2 + 3] reaction with 2-amino-1,4-naphthoquinone (eq 9),13f a solvent-dependent photochemical cycloaddition with o-naphthoquinones,13j and reaction with 2-nitro-1,3-dienes to provide a,b-unsaturated 1,4-diones (eq 10).13g
2-Methoxyallyl and -vinyl halides are formed by reaction of 2-MP with N-halosuccinimides.14 Also, treatment of propargylic alcohols with 2-MP and N-Bromosuccinimide results in the formation of bromo acetals, which are subsequently cyclized to furans in good yield (eq 11).4b
K. Sinclair Whitaker
Wayne State University, Detroit, MI, USA
D. Todd Whitaker
Detroit County Day School, Beverly Hills, MI, USA