1-Methoxy-1,2-propadiene

[13169-00-1]  · C4H6O  · 1-Methoxy-1,2-propadiene  · (MW 70.10)

(undergoes lithiation and reaction with electrophiles at C-1,1 hetero-Diels-Alder2 and dipolar3 cycloadditions, and transition metal-catalyzed,4,5 radical,6 and electrophilic7 addition reactions)

Alternate Name: methoxyallene.

Physical Data: bp 51-52 °C.

Solubility: sol THF, ether, pentane, hexane, CH2Cl2, CHCl3, DMSO.

Analysis of Reagent Purity: 1H NMR (CDCl3) d 6.77 (1H, t, J = 5.9 Hz), 5.48 (2H, d, J = 5.9 Hz), 3.42 (3H, s).

Preparative Methods: not commercially available, but can be prepared1 on a tens-of-grams scale by the base-catalyzed isomerization of 1-methoxy-2-propyne (methyl propargyl ether) (eq 1). Related 1-alkoxy-1,2-propadiene ethers can be prepared similarly. A convenient version of this preparation has been reported.8

Purification: by distillation.

Metalation.

Many applications of 1-methoxy-1,2-propadiene require that it be converted to lithiated,1,9-11 magnesiated,12 zincated,13 or cuprated14 derivatives. Some of the conditions reported for effecting metalations at C-1 are summarized in eq 2.

Owing to the steric requirement of the t-Bu substituent, lithiation can be directed with considerable selectivity to C-3 in 1-t-butoxy-1,2-propadiene (eq 3).15,16 A minor amount of lithiation at C-1 occurs in this procedure. Related metalated intermediates of some significance in synthesis include (3)16-20 and (4).19

Reaction of Electrophiles with Metalated Derivatives.

Through the intervention of metalated derivatives of the type described in the previous section, 1-methoxy-1,2-propadiene and related allene ethers function as synthesis equivalents for the conventionally unavailable acryloyl acyl (5) and b-acryloyl (6) anions, and acryloyl dianion (7). These equivalencies depend on the electrophilic modification of derivatives like (1), (2),15,16 and (3)16-20 (eqs 4-6).

Examples of the capture of (1) (Met = Li) by relatively simple electrophiles16,21-23 include those in eqs 7-10.9,17,18,20,24-30 These invariably involve electrophilic attack at C-1 rather than C-3 in this potentially ambident nucleophile. (1) also engages in transition metal-mediated processes that elaborate the C-1 position (eqs 11 and 12).11,31,32

Hetero-Diels-Alder Cycloadditions.

The literature contains several examples of hetero-Diels-Alder reactions involving 1-methoxy-1,2-propadiene wherein inversion of the conventional electronic roles of the 4p and 2p components occurs. Reactions of this reagent with vinyl nitroso compounds,33,34 unsaturated aldehydes and ketones,35-37 and unsaturated sulfonimines2,38 (eq 13) have been reported. The endo selectivity witnessed in the sulfonimine reactions is to be contrasted with an example of exo selectivity involving a vinyl nitroso coreactant.33 The oxygenated double bond of the reagent is invariably attacked, and is intermediate in its reactivity relative to ethyl vinyl ether (more reactive) and trimethylsilyl vinyl ether (less reactive).39

Dipolar Cycloadditions.

This reagent likewise is reactive toward appropriate 4p components in dipolar cycloadditions. Examples involving nitrile imines,40 nitrile oxides,41 and diazo compounds3 (eq 14) have been reported. The characteristic regioselectivity in this cycloaddition class differs from that described above.

Copper-Mediated Additions of Organometallic Reagents.

A mixture of this reagent and a catalytic amount of a copper(I) halide effects the propargylation of Grignard reagents, a process that involves a formal SN2 displacement of the methoxy group (eq 15).4,42,43 However, when the stoichiometric ratio of the copper(I) halide to the Grignard reagent (RMgX) is increased, simple addition products of the type RCH2CH=CHOMe are delivered after aqueous workup.44 In the latter cases, larger R groups lead to increased proportions of the (E)-enol ether products.

An unusual copper-mediated addition process has been devised whereby two methylene groups derived from Iodomethylzinc Iodide are added across the 1,2-double bond of 1-methoxy-1,2-propadiene to give an organometallic intermediate that can be trapped by aldehydes and ketones (eq 16).14

Other Transition Metal-Mediated Additions.

Palladium and molybdenum catalyze the addition of tin, silicon, and germanium reagents of the type R16Sn2,45,46 R13SiSnR23,45,47 R13GeSnR23,48 and R13SnH47,49 to 1-methoxy-1,2-propadiene. The addition reagent, the metal, and the size of the R1 and R2 groups all play roles in determining the regio- and stereoselectivity of these reactions (eqs 17 and 18).45,47 For example, the regioselectivity shown in eq 17 for attack at the nonoxygenated double bond is reversed in an example involving n-Bu3SnGeMe3.48 The stereo- and regioselectivity in eq 18 are much superior to those of the radical addition that produces the same materials (see below).

Transition metal-mediated transformations that involve 1-methoxy-1,2-propadiene in the creation of new carbon-carbon bonds, but which are difficult to classify, have been reported.50,51 However, a few examples that occur by way of palladium (eq 19)5 and iron catalysis52,53 appear to be related.

Radical Additions.

Tri-n-butylstannane adds nonselectively in radical fashion to 1-methoxy-1,2-propadiene to give, among other products, a low yield of the enol ethers that arise from attachment of the tin to C-3.47 In contrast, both Diphenylphosphine54 and Thiophenol (eq 20; product ratio reflects equilibrium mixture of geometrical isomers)6 add selectively to the central C-2 carbon, a reflection of the intermediacy of allylic radicals.

Electrophilic Additions.

The p-electron-rich character of this reagent conferred by its alkoxy group makes it highly reactive in processes initiated by the addition of an electrophile. Interesting examples include eqs 21 and 22,7,55 wherein it can be seen that the nucleophilic reaction partner can attach itself either to C-1 or to C-3. A number of additional applications of this reaction type require 1-methoxy-1,2-propadiene to provide a mixed acetal when exposed to an appropriate nucleophile in the presence of an electrophilic initiator.56


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Charles Swindell

Bryn Mawr College, PA, USA



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