[88248-68-4]  · C9H21N3  · t-Butyltetramethylguanidine  · (MW 171.29)

(strong base for formation of aziridines, alkylation, nitronation)

Physical Data: bp 80-82 °C/20 mmHg.

Form Supplied in: colorless liquid.

Preparative Method: prepared via reaction of t-Butylamine with the highly hygroscopic Vilsmeier salt obtained by reaction of N,N,N,N-tetramethylurea and Phosgene.1-3

t-Butyltetramethylguanidine (1) is one of a range of hindered pentaalkylguanidines prepared by Barton for use as strong bases, and has been used in aziridine formation in a series of cholesterol derivatives (such as the conversion of (2) to (3), eq 1).4

The reagent is particularly useful in the preparation of esters of sterically compromised acids via the alkylation of their carboxylate salts (eqs 2 and 3). Thus the extremely hindered carboxyl group of hederagenin is converted efficiently to its methyl ester (4).3 Keto acid (5) is esterified in similarly productive fashion.5

The reagent successfully effects monoalkylation of b-keto esters (eq 4). No O-methylation is observed in this reaction.3

The conjugate addition of nitronate anions to oxidized naphthalenes such as (6) occurs smoothly in the presence of (1) (eq 5);6 use of Triethylamine led to substantial decomposition of starting materials.

The reagent also proves significantly superior to triethylamine in the conversion of hydrazones to vinyl iodides (eq 6).7

The above reaction was examined using a variety of bases (eq 7); use of (1) gave best overall yields of iodide (7) and also minimized formation of azine byproduct (8) (Table 1).8

In the reaction of camphor-derived hydrazones, the use of (1) was essential to prevent rearrangement (eqs 8 and 9).8 When triethylamine was employed in place of (1), rearranged allylic iodide (9) became the major product.

The use of (1) in the arylation of 2-naphthol using tetraphenylbismuth esters completely suppresses the O-arylation, which is otherwise a troublesome side reaction (eq 10).9

In the reduction of nitro compounds to oximes, the exceptional basicity of (1) is problematic (eq 11); for instance, the desired oxime (10) is obtained as the minor product (23%) and the major product is the nitrile (11), the product of over reaction.10

The reagent participates in a mild Nef reaction in the presence of Diphenyl Disulfide and a secondary nitroalkane such as (12) (eq 12).11

Nitroalkanes are again the substrates for the tetraalkylguanidine-mediated synthesis of trisubstituted pyrroles (13) invented by Barton et al (eq 13). The reagent gives better yields in a shorter reaction time than with 1,8-Diazabicyclo[5.4.0]undec-7-ene.12

The salt (14) obtained from the reaction of (1) and m-iodoxybenzoic acid oxidizes nitronate anions at rt to give the corresponding carbonyl compounds (eq 14). Once again, DBU gives comparable results but the yields of the reaction are lower.13 Salt (14) is also able to cleave glycols under extremely mild conditions.14

1. Kessler, H.; Liebfritz, D.; Burk, C. T 1970, 26, 1805.
2. Barton, D. H. R.; Elliot, J. D.; Géro, S. D. CC 1981, 1136.
3. Barton, D. H. R.; Elliot, J. D.; Géro, S. D. JCS(P1) 1982, 2085.
4. Barton, D. H. R.; Hay-Motherwell, R.; Motherwell, W. B. JCS(P1) 1983, 445.
5. Barton, D. H. R.; Godfrey, C. R. A.; Morzycki, J. M.; Motherwell, W. B.; Ley, S. V. JCS(P1) 1982, 1947.
6. Arzeno, H.; Barton, D. H. R.; Bergé-Lurion, R-M.; Luschini, X.; Pinto, B. M. JCS(P1) 1984, 2069.
7. Barton, D. H. R.; Bashiardes, G.; Fourrey, J.-L. TL 1983, 24, 1605.
8. Barton, D. H. R.; Bashiardes, G.; Fourrey, J.-L. T 1988, 44, 147.
9. Barton, D. H. R.; Charpiot, B.; Motherwell, W. B. TL 1982, 23, 3365.
10. Barton, D. H. R.; Fernandez, I.; Richard, C. S.; Zard, S. A. T 1987, 551.
11. Barton, D. H. R.; Motherwell, W. B.; Simon, E. S.; Zard, S. A. JCS(P1) 1986, 2243.
12. Barton, D. H. R.; Zard, S. A. CC 1985, 1089.
13. Barton, D. H. R.; Motherwell, W. B.; Zard, S. A. TL 1983, 24, 5227.
14. Barton, D. H. R.; Godfrey, C. R. A.; Morzycki, J. M.; Motherwell, W. B.; Stobie, A. TL 1982, 23, 957.

Joseph Sweeney

University of Bristol, UK

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