(2-Dimethylaminoethyl)triphenylphosphonium Bromide

[21331-80-6]  · C22H25BrNP  · (2-Dimethylaminoethyl)triphenylphosphonium Bromide  · (MW 414.33)

(precursor to dimethylaminoethylidenetriphenylphosphorane, which condenses with aldehydes and ketones to give allylic amines1)

Physical Data: mp 201 °C.

Form Supplied in: white solid; widely commercially available.

Preparative Methods: this reagent and analogous N,N-dialkylaminoethyltriphenylphosphonium bromides are prepared by condensation of the corresponding b-amino alcohols with Triphenylphosphine in the presence of Hydrogen Bromide.1

Purification: recrystallization from acetic acid-chloroform.

Handling, Storage, and Precautions: should be dried in vacuo for best results.

Reaction with Aldehydes and Ketones.

The ylide derived from deprotonation of (2-dimethylaminoethyl)triphenylphosphonium bromide with n-Butyllithium reacts with a wide variety of aldehydes and ketones in a modified Wittig reaction to yield the homologated unsaturated amine (eq 1).

The stereoselectivity of this reaction with aromatic aldehydes has been investigated and conditions have been described for the selective formation of either alkene isomer (eqs 2 and 3).1,2

The ylide reacts readily with both unactivated and hindered ketones to give products such as (1)-(3) and, in the case of unsymmetrical ketones, can show impressive levels of stereoselectivity.1,3,4

Related Reagents.

Attempts to extend this reaction by using the analogous ylide generated from (2-methylaminoethyl)triphenylphosphonium bromide (4) are plagued by low chemical yields.1 In contrast, treatment of the phosphonium salt (4) with two equivalents of BuLi generates the dianion that reacts with aldehydes to give the secondary allylic amines in high chemical yields with a modest preference for the (E) alkene isomer.5

The phosphine oxide (5) has also been developed for the stereoselective synthesis of allylic amines.6 Condensation of the lithium anion of this reagent with ketones gives an equal mixture of the syn and anti addition products which can typically be separated by chromatography or distillation. The individual diastereomers are then subjected to a syn elimination protocol to provide the individual (E) and (Z) allylic amines in good overall chemical yields.

1. Marxer, A.; Leutert, T. HCA 1978, 61, 1708.
2. For a discussion of the stereoselectivity of phosphonium ylides containing nucleophilic substituents, see: (a) Maryanoff, B. E.; Reitz, A. B. CRV 1989, 89, 863. (b) Maryanoff, B. E.; Reitz, A. B.; Duhl-Emswiler, B. A. JACS 1985, 107, 217.
3. Hickmott, P. W.; Wood, S.; Murray-Rust. P. JCS(P1) 1985, 2033.
4. Carnmalm, B.; De Paulis, T.; Högberg, T.; Johansson, L.; Persson, M. L.; Thorberg, S. O.; Ulff, B. ACS(B) 1982, B36, 91.
5. Lindermann, R. J.; Meyers, A. I. TL 1983, 24, 3043.
6. (a) Cavalla, D.; Warren, S. TL 1982, 23, 4505. (b) Cavalla, D.; Warren, S. TL 1983, 24, 295.

David M. Armistead

Vertex Pharmaceuticals, Cambridge, MA, USA

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