(Methylphenylamino)triphenylphosphonium Iodide

[34257-63-1]  · C25H23INP  · (Methylphenylamino)triphenylphosphonium Iodide  · (MW 495.36)

(synthesis of amines from alcohols; synthesis of unsymmetrical sulfides; synthesis of alkenes from allyl alcohols; synthesis of 1,3-dienes)

Alternate Name: Murahashi's reagent.

Physical Data: mp 237-242 °C (dec); commercial material quotes a higher melting point than material made in the reference.1

Solubility: sol DMF, EtOAc. Behaves as a Wittig-type reagent in terms of solubility.

Form Supplied in: solid.

Preparative Method: phenyliminotriphenylphosphorane is reacted with excess Iodomethane at reflux for 2 h. Removal of MeI followed by recrystallization gives a quantitative yield.1

Purification: may be recrystallized from chloroform-ethyl acetate (1:2).

Handling, Storage, and Precautions: store in sealed bottle on bench. Do not breathe dust, fumes, or vapor. Avoid contact with skin and eyes. Use in a fume hood.

Synthesis of Amines from Alcohols.

The reagent is similar to the Mitsunobu reagent in that it converts alcohols to alkylating agents. Hence, the reaction of an alkoxide ion with Murahashi's reagent in the presence of a primary or secondary amine leads to N-alkylation in high yield.2 The reaction is mild and high yielding (eq 1), although replacing benzene for DMF as a solvent for secondary amines is recommended. Analogously, the preparation of azides can be accomplished by using Sodium Azide as the nucleophile.

Synthesis of Unsymmetrical Sufides.

Unsymmetrical sulfides may also be prepared by the reaction of alkoxides and thiols utilizing aminophosphoranes (eq 2). This method has been applied to the synthesis of various thiols, e.g. alkyl, benzyl, phenyl, t-butyl, and vinyl thiols.3 Both cis- and trans-cinnamyl alcohols have been used, as well as geraniol, yielding the corresponding sulfides with retention of configuration.

Synthesis of Alkenes from Allyl Alcohols.

Allylic alcohols may be alkylated by an excess of alkyllithium in the presence of Methyllithium, Copper(I) Iodide, and Murahashi's reagent (eq 3).4 The detailed structure of the lithium alkoxyallylcuprate and alkylcuprate having the stoichiometry R1OCuR23Li3 is not known.

g-Alkylation of allylic alcohols with organolithium reagents using (methylphenylamino)tributylphosphonium iodide proceeds as shown in eq 4.5 The latter reagent is easily prepared by addition of Phenyl Azide to Tri-n-butylphosphine in refluxing ether, followed by treatment with Iodomethane at reflux (90% yield; mp 120-120.5 °C, recrystallized from ethyl acetate.

Thus the reaction provides an efficient single-step process for the regio- and stereoselective synthesis of alkenes. Excellent yields are obtained from primary, secondary, and tertiary alcohols. Importantly, 1-substituted 2-propen-1-ols, which are readily available, can be converted into trans-1,2-disubstituted alkenes in a regio- and stereospecific manner. Alkylation of tertiary alcohols occurs with predominant allylic rearrangement, giving trisubstituted alkenes. The cis/trans ratios of the alkenes are not dependent upon the substitution of the tertiary allylic alcohol nor upon the organolithium compound; constant values of 32-36/68-64 are obtained. A reinvestigation of the regio- and stereochemistry was carried out by Goering.6 In the initial study, triphenylphosphorane derivatives were used and there was no indication of any regiospecificity. More recently, tributylphosphorane salts have been used and SN2 regiospecificity is observed (eq 5).

It is reported that the differences in regiochemistry do not result from using different phosphoranes, but instead result from a change in the experimental procedure. In fact, under the same conditions, the regio- and stereochemistry are the same with both reagents: this would be expected if the mechanistic pathway proposed by Murahashi5 (eq 6) is followed.

In a further study of the alkylation of acylic systems by the same group,7 it was found that syn g-alkylation predominates in acyclic systems, but anti g-alkylation predominates in cyclic systems. The results show that the reaction is highly regioselective.

Synthesis of 1,3-Dienes.

Alkylation of a-allenic alcohols by organolithiums using Murahashi's reagent leads to formation of 1,3-dienes (eq 7).8 This allows direct nucleophilic substitution of labile or hindered a-allenic alcohols by organolithium reagents; the yields are in the range 35-55%.

This procedure invoves the in situ transformation of the hydroxy group of an unsaturated alcohol into an alkoxyphosphonium salt and the reaction of this with a nucleophile. The stereoselectivity seems to be dependent on the nucleophile and the nature of the substituent on the a-allenic carbon atom. The main interest of the reaction lies in the possibility of using various carbonucleophiles.

A review has appeared in the literature concerning the utility of the reagent in preparation and nucleophilic substitution of the hydroxy group of alcohols in organic synthesis.8

1. Tanigawa, Y.; Kanamaru, H.; Sonoda, A.; Murahashi, S-I. JACS 1977, 99, 2361.
2. Tanigawa, Y.; Murahashi, S-I.; Moritani, I. TL 1975, 471.
3. Tanigawa, Y.; Kanamaru, H.; Murahashi, S-I. TL 1975, 4655.
4. Tanigawa, H.; Ohta, H.; Sonoda, A.; Murahashi, S-I. JACS 1978, 100, 4610.
5. Goering, H. L.; Kantner, S. S. JOC 1981, 46, 2144.
6. Goering, H. L.; Tseng, C. C. JOC 1985, 50, 1597.
7. Fan, C.; Cazes, B. TL 1988, 29, 1701.
8. Murahashi, S-I; Imada, Y. Yuki Gogei Kagaku Kyokaishi 1990, 48, 1056.

Sean Bew, Gemma Perkins & Susan Champion

University of Bristol, UK

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