1-Methoxyallenyllithium1

[61186-66-1]  · C4H5LiO  · 1-Methoxyallenyllithium  · (MW 76.03)

(acryloyl carbanion equivalent; reagent for the synthesis of a,b-unsaturated carbonyl compounds, methoxybutadienes, acylsilanes, methoxycyclopropanes; reagent for annulation of 2-furanones, methoxyfurans, methylenecyclopentanones, and hydroxyquinones)

Alternate Name: (1-methoxy-1,2-propadienyl)lithium.

Physical Data: parent allene: bp 51.5-52.5 °C/760 mmHg;2 nD20 1.4264;2 1H NMR (CDCl3) d 6.77 (t, J = 5.9 Hz, 1 H), 5.48 (d, J = 5.9 Hz, 2 H), 3.42 (s, 3 H).3

Preparative Methods: methoxyallene2,4 is easily prepared from Propargyl Alcohol by conversion to the methyl ether with aqueous Sodium Hydroxide and Dimethyl Sulfate followed by treatment with finely powdered Potassium t-Butoxide for 2-3 h at 70 °C. The overall yield of methoxyallene, following vacuum distillation, is 82% (eq 1).5 Use of a heating mantle should be avoided; uneven heating during the isomerization or the distillation leads to polymerization of the sensitive allene. The allene can be stored over K2CO3 at -20 °C for several weeks without appreciable decomposition. Abstraction of the a-hydrogen atom from methoxyallene takes place rapidly on treatment with n-Butyllithium in ether at -30 °C.6

Handling, Storage, and Precautions: the parent allene is best stored at -20 °C, or below, over anhydrous K2CO3. Hydrolysis or polymerization take place in the presence of acid.

Introduction.

1-Methoxyallenyllithium (1) is a reactive nucleophile which functions as an acryloyl anion equivalent in its reactions with electrophiles.

Carbonyl Addition Reactions.3

Addition of (1) to cyclohexanone and hydrolysis of the methyl enol ether gives the hydroxy enone in 92% yield (eq 2).6 The addition of (1) to chiral aldehydes shows good anti selectivity (eq 3).7 The stereochemical preference for addition has been rationalized according to the Felkin-Anh model. Exposure of the major adduct to catalytic potassium t-butoxide leads to the 2,5-dihydrofuran derivative, which can be hydrolyzed to the furanone. Considerable attention has been focused on this unusual transformation.8 The cyclohexenone adduct of (1) undergoes base-catalyzed conversion to the methoxydihydrofuran in what is formally a rare 5-endo-digonal cyclization (eq 4). It is noteworthy that no [1,3]- or [3,3]-sigmatropic rearrangements take place, even though these are not obviously precluded by geometrical constraints.8

Chelation controlled addition of (1) to carbonyl compounds is also known. Cleavage of the amine protecting group in the proline-derived ketone (2) results in a labile amino ketone (eq 5).9 Addition of (1) to this ketone leads to a single product which is converted to the bicyclic methyl enol ether (3) by exposure to slightly less than 1 equiv of dry p-Toluenesulfonic Acid in acetonitrile at 23 °C.

Addition of (1) to 3-chloro-2-butanone (eq 6), followed by brief exposure of the product to Potassium Hydroxide, leads to an epoxy allene.10 Rearrangement to 3-methoxy-2,4,5-trimethylfuran is accomplished by treatment with base. The mechanism is postulated to proceed by initial abstraction of a vinyl hydrogen with epoxide ring opening, leading to an intermediate enynol which undergoes base-catalyzed cyclization to the furan.

Additions to Alkyl Halides.

A convergent synthesis of a,b-unsaturated ketones makes use of (1) (eq 7).11 Alkylation of (1) with a primary alkyl halide at C-1 is followed by deprotonation of the allene product at C-3 with n-butyllithium.2 Quenching of the 1-methoxy-3-lithioallene with a second alkyl halide and hydrolysis of the product forms enones in excellent overall yield. The 1-methoxy-3-lithioallene can be intercepted by a variety of electrophiles (eq 8).12 This work demonstrates the utility of (1) both as an a- and as a g-acyl anion equivalent. The kinetic preference for the exclusive formation of the (Z)-keto ester (eq 8) is noteworthy, and is the result of stereoelectronic control during the protonation step.

The products of alkylation of (1) with alkyl halides can be rearranged to methoxy dienes (eq 9). Exposure of the adducts to Pyridinium p-Toluenesulfonate at rt produces 1-substituted 2-methoxybutadienes in moderate yield with good selectivity for the (E) isomer.13

More highly substituted methoxybutadienes are also accessible through (1). The adducts of (1) with carbonyl compounds (eq 10) are converted to the methanesulfinate ester derivatives.14 Copper-catalyzed Grignard addition takes place selectively at the sp-hybridized carbon of the allene with displacement of methanesulfinate to produce 2-alkyl- or 2-aryl-3-methoxy-1,3-dienes in 70-95% overall yield (eq 10). Enol ether hydrolysis gives enones. Homocuprates are unsatisfactory in this instance because they attack the sulfur atom preferentially.

The alkylation products of (1) are useful for the synthesis of dioxaspiro compounds. For example, the allene (4), which is available in quantitative yield from (1), can be deprotonated with t-Butyllithium, and the g-anion trapped with Ethylene Oxide in 88% yield (eq 11).15 Silyl protecting group cleavage, followed by mild, acid-catalyzed intramolecular acetalization, leads to a mixture of diastereoisomeric dioxaspiro compounds. Where additional control elements are present in the rings, the reaction can be biased toward a single product.16

The trapping of (1) by heteroatomic electrophiles to give (5) has been described.6,17-19

Reaction with Trialkylboranes.

An unusual synthesis of methoxycyclopropanes which proceeds from (1) has been disclosed (eq 12).20 Exposure of the 9-BBN (see 9-Borabicyclo[3.3.1]nonane) adduct of 1-methylcyclohexene to a small excess of (1), followed by acidification and oxidative workup, leads to the methoxycyclopropane in high yield. The mechanism presumably involves acid-catalyzed rearrangement of a lithium borate salt, accompanied by allylic migration of boron. This is supported by the observation that use of deuterioacetic acid results in the formation of a methoxycyclopropane product in which one methylene group of the three-membered ring is fully deuterated.

Related 1-Alkoxyallenyllithiums and Reactions.

1-(1-Ethoxyethoxy)allenyllithium (6)2 has been used to convert an aldehyde into an a,b-alkynic ketone (eq 13).21 Aldehyde addition and quenching of the alkoxide with Chlorotrimethylsilane, followed by treatment with n-butyllithium, leads to trimethylsilyl oxide elimination and generation of the ketone enol ether. The allenyllithium (6) has also been used for the preparation of acylsilanes.22 Trapping with t-Butyldimethylchlorosilane leads to the allenylsilane which upon hydrolysis gives the silyl enone, and upon treatment with peroxy acid gives 1-t-butyldimethylsilyl-1,2-propanedione, presumably through an allene oxide intermediate (eq 14).

1-(Methoxymethoxy)allenyllithium (7) has been used in a cationic cyclopentannulation reaction.23 Addition of (7) to 3-methyl-2-buten-1-one produces a tertiary alcohol which cyclizes to a five-membered ring upon treatment with Trifluoroacetic Anhydride and 2,6-2,6-Lutidine (eq 15) in a process reminiscent of the Nazarov reaction. The success of the cyclization reaction requires that the oxygen substituent on the allene be capable of departing as a stable cation.24

Addition of (7) to the vinylogous silyl ester (8), followed by treatment of the product with fluoride, produces a tertiary allenic alcohol (eq 16). Epoxidation with buffered peroxy acid produces an epoxy keto aldehyde, presumably from intramolecular trapping of an oxyallyl zwitterion. Methanolic KOH leads to a hydroxy quinone which is O-methylated with Diazomethane.25 Treatment of the adduct of (7) and (8) with Boron Trifluoride Etherate in dichloromethane leads to the cyclopentannulation product (eq 17).26

Related Anions.

Trialkylsilyloxyallenes can be prepared from 2,2-dimethyl-4-methylene-1,3-dioxolane (eq 18).27 Deprotonation with 2 equiv s-Butyllithium leads to the allylic carbanion which fragments to the lithium alkoxide of 1,2-propadien-1-ol. Quenching with t-Butyldiphenylchlorosilane leads to the siloxyallene in high overall yield. Allene deprotonation takes place under the same conditions as for (1).

The allenyllithium (10) is prepared selectively in 80% yield, along with 5-6% of (9), by g-deprotonation of t-butoxyallene with sterically encumbered lithium dicyclohexylamide.11 Deprotonation of 1-phenylthioprop-1-yne with n-butyllithium/TMEDA at -78 °C leads to thiophenoxyallenyllithium (11).28 Anion (12) bears asymmetry on the ether sidechain. Modest levels of asymmetric induction are found in the addition reactions of (12) with ketones.29 1-Methoxy-1,2,3-butatrienyllithium (13) is prepared by treating 1,4-dimethoxy-2-butyne with 2 equiv n-butyllithium at -78 °C and warming to -45 °C.30 This reagent has been used for a synthesis of enynes. The related lithioallenes (14)-(16)24 and the copper derivative (17)31 have also been described.

Related Reagents.

Allenyllithium; 1-Trimethylsilyl-1-methoxyallene.


1. (a) Huché, M. BSF(2) 1978, 313. (b) Zimmer, R. S 1993, 165. (c) Schuster, H. F.; Coppola, G. M. Allenes in Organic Synthesis; Wiley: New York, 1984; pp 215-224.
2. Hoff, S.; Brandsma, L.; Arens, J. F. RTC 1968, 87, 916.
3. Weiberth, F. J.; Hall, S. S. JOC 1985, 50, 5308.
4. Methoxyallene is available from Merck-Schuchardt.
5. The trideuteriomethyl analog has been described: Kamphuis, J.; Ruijter, A. P.; Bos, H. J. T. JCS(P2) 1987, 907.
6. Hoff, S.; Brandsma, L.; Arens, J. F. RTC 1968, 87, 1179.
7. Hormuth, S.; Reissig, H.-U. SL 1991, 179.
8. (a) Gange, D.; Magnus, P. JACS 1978, 100, 7746. (b) Gange, D.; Magnus, P.; Bass, L.; Arnold, E. V.; Clardy, J. JACS 1980, 102, 2134.
9. Overman, L. E.; Goldstein, S. W. JACS 1984, 106, 5360.
10. Schreurs, P. H. M.; Meijer, J.; Vermeer, P.; Brandsma, L. TL 1976, 17, 2387.
11. Clinet, J.-C.; Linstrumelle, G. TL 1978, 18, 1137.
12. Derguini, F.; Linstrumelle, G. TL 1984, 25, 5763.
13. Kucerovy, A.; Neuenschwander, K.; Weinreb, S. M. SC 1983, 13, 875.
14. Kleijn, H.; Westmijze, H.; Vermeer, P. TL 1978, 18, 1133.
15. (a) Kocienski, P.; Whitby, R. S 1991, 1029. (b) Whitby, R.; Kocienski, CC 1987, 906.
16. Takle, A.; Kocienski, P. TL 1989, 30, 1675.
17. Clinet, J.-C.; Linstrumelle, G. TL 1980, 21, 3987.
18. Zimmer, R.; Reissig, H.-U. LA 1991, 553.
19. Oostveen, J. M.; Westmijze, H.; Vermeer, P. JOC 1980, 45, 1158.
20. Miyaura, N.; Yoshinari, T.; Itoh, M.; Suzuki, A. TL 1980, 21, 537.
21. Stork, G.; Nakamura, E. JACS 1983, 105, 5510.
22. Reich, H. J.; Kelly, M. J.; Olson, R. E.; Holtan, R. C. T 1983, 39, 949.
23. Tius, M. A.; Astrab, D. P.; Fauq, A. H.; Ousset, J.-B.; Trehan, S. JACS 1986, 108, 3438.
24. Tius, M. A.; Ousset, J.-B.; Astrab, D. P.; Fauq, A. H.; Trehan, S. TL 1989, 30, 923.
25. Tius, M. A.; Cullingham, J. M.; Ali, S. CC 1989, 867.
26. Tius, M. A.; Astrab, D. P. TL 1984, 25, 1539.
27. Tius, M. A.; Astrab, D. P.; Gu, X. JOC 1987, 52, 2625.
28. (a) Bridges, A. J.; Thomas, R. D. CC 1983, 485. (b) Bridges, A. J.; Thomas, R. D. CC 1984, 694.
29. Rochet, P.; Vatéle, J.-M.; Goré, J. SL 1993, 105.
30. Koshino, J.; Sugawara, T.; Suzuki, A. SC 1984, 14, 245.
31. Sidduri, A.; Rozema, M. J.; Knochel, P. JOC 1993, 58, 2694.

Marcus A. Tius

University of Hawaii, Honolulu, HI, USA



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