[78551-14-1]  · C8H13NO4  · 2-Nitro-3-pivaloyloxypropene  · (MW 187.22)

(multicoupling reagent; reacts stepwise with two different nucleophiles1)

Alternate Name: NPP.

Physical Data: mp 18 °C; bp 40-45 °C/0.01 mmHg.

Solubility: sol all organic solvents; decomposes in pyridine and slowly in protic solvents.

Preparative Method: prepared in four steps from Formaldehyde, Nitromethane, and pivaloyl chloride (ca. 25% overall yield at a 0.7 mol scale).1

Handling, Storage, and Precautions: can be stored six months at -10 °C without decomposition. Use in a fume hood.

Selective Multicoupling Reagent.

2-Nitro-3-pivaloyloxypropene (NPP) is an exceptionally reactive nitroalkene, since both the nitro group and the allylic pivaloyloxy group contribute to enhance the acceptor properties of the double bond. It reacts under very mild conditions with a broad range of nucleophiles producing polyfunctional nitroalkenes which under the reaction conditions do not react further with the nucleophile added (eq 1).1-3 The resulting nitroalkenes can react with a different second nucleophile, providing highly functionalized nitroalkanes (eq 2).3 They also can be converted into ketones by a Nef reaction (eq 3)3 or reduced to amines.3 NPP readily undergoes Diels-Alder reactions with various dienes; after an elimination reaction, cyclic enol pivalates are obtained (eqs 4 and 5).4 The related reagent 2-nitro-3-acetoxypropene can also be prepared. It reacts selectively with the functionalized zinc-copper reagents RCu(CN)ZnI (eq 6).5

Substituted NPP Reagents.

A wide range of substituted NPP reagents can be prepared regio- and enantioselectively.6,7 They display the same reactivity pattern (eqs 7 and 8)7 and can be used for performing highly diastereoselective cyclizations with chiral enamines (eq 9)8,9 or b-enamino esters (eq 10).10

Interestingly, using enzymatic methods, the preparation of enantiomerically pure NPP derivatives becomes possible.11,12 These chiral reagents have been used successfully for performing the above-mentioned [3 + 3] carbocyclization.9 The NPP reagents demonstrate well the synthetic utility of multicoupling building blocks in organic synthesis.13,14

1. Seebach, D.; Knochel, P. HCA 1984, 67, 261.
2. Knochel, P.; Seebach, D. NJC 1981, 5, 75.
3. Knochel, P.; Seebach, D. TL 1981, 22, 3223.
4. Knochel, P. PhD Thesis, ETH Zürich 1982, No. 7170.
5. Jubert, C.; Knochel, P. JOC 1992, 57, 5431.
6. Knochel, P.; Seebach, D. TL 1982, 23, 3897.
7. Seebach, D.; Calderari, G.; Knochel, P. T 1985, 41, 4861.
8. Seebach, D.; Calderari, G.; Meyer, W. L.; Merritt, A.; Odermann, L. C 1985, 39, 183.
9. Seebach, D.; Missbach, M.; Calderari, G.; Eberle, M. JACS 1990, 112, 7625.
10. Lapierre, J. M.; Gravel, D. TL 1991, 32, 2319.
11. Seebach, D.; Eberle, M. C 1986, 40, 315.
12. Eberle, M.; Egli, M., Seebach, D. HCA 1988, 71, 1.
13. For pioneering work see: (a) Nelson, R. P.; Lawton, R. G. JACS 1966, 88, 3884. (b) Nelson, R. P.; McEuen, J. M.; Lawton, R. G. JOC 1969, 34, 1225. (c) McEuen, J. M.; Nelson, R. P.; Lawton, R. G. JOC 1970, 35, 690.
14. (a) Auvray, P.; Knochel, P.; Normant, J. F. T 1988, 44, 4495. (b) Auvray, P.; Knochel, P.; Normant, J. F. T 1988, 44, 4509. (c) Padwa, A.; Kline, D. N.; Murphree, S. S.; Yeske, P. E. JOC 1992, 57, 298. (d) Seta, A.; Tokuda, K.; Sakakibara, T. TL 1993, 34, 3433.

Paul Knochel

Philipps-Universität Marburg, Germany

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