Methyltriphenoxyphosphonium Iodide1

(PhO)3+PMe I-

[17579-99-6]  · C19H18IO3P  · Methyltriphenoxyphosphonium Iodide  · (MW 452.24)

(reagent for selective conversion of alcohols to alkyl iodides;4c,13c effects dehydration of alcohols14a and dehydrohalogenation of alkyl halides15a to alkenes; deoxygenates epoxides to alkenes17)

Alternate Names: MTPI; triphenyl phosphite methiodide; triphenoxy(methyl)phosphonium iodide.

Physical Data: mp 146 °C.

Solubility: sol CH2Cl2, DMF, MeCN, THF, HMPA, DMI (1,3-dimethyl-2-imidazolidinone); sl sol PhH.

Form Supplied in: amber to white crystals; commercially available; purity >95%; typical impurity: MeP(O)(OPh)2 (see analytic data below).

Analysis of Reagent Purity: IR (film): 1600, 1500 (Ph), 1160, 980 (P-O-C), 770, 690 (Ph); 1H NMR (CDCl3): 3.1 (d, 3H, JP,Ha = 16.5 Hz, Me), 7.45 (m, 15H, OPh). 31P NMR (CHCl3): +41 ± 1 (q). MeP(O)(OPh)3: 1H NMR (CDCl3): 1.8 (d, JP,Ha = 18 Hz, Me), 7.2 (m, OPh); 31P NMR (CHCl3): +24 ± 1 (q).

Preparative Methods: further improvements13c have been introduced to the original preparation.4c

Purification: commercial or synthesized material can, if necessary, be purified by washing with EtOAc or by repetitive (×3) precipitation of the reagent from a CH2Cl2 or MeCN solution with ether; the almost colorless solid so obtained is filtered and dried in vacuo.

Handling, Storage, and Precautions: harmful material which may cause irritation; should be handled under N2 in a dry box; keep container closed; light and moisture sensitive; store in the dark, under N2 in a cool dry place; avoid breathing dust and contact with eyes, skin, and clothing; incompatibility: strong oxidizing agent.

Introduction.

First described at the beginning of the century2 the adduct of Triphenyl Phosphite and Iodomethane was further developed for use in synthesis 50 years later4 and has been widely used since that time. Stable in the absence of moisture, the oxyphosphonium salt MTPI behaves unlike the alkyloxyphosphonium halide analogs; these latter reagents undergo nucleophilic displacement with their own counterions, unless very bulky substituents are involved,3b via the Michaelis-Arbuzov reaction. The stability of MTPI arises from the inability of the phenyl group to suffer nucleophilic substitution. 31P NMR data3 clearly suggest the ionic tetracovalent nature of phosphorus in MTPI.

Preparation of Alkyl Iodides.

In 1951 it was reported4a that the Michaelis' salt MTPI reacts with alcohols to form alkyl iodides with release of PhOH and MeP(O)(OPh)2. The reaction appears to involve initial displacement of a phenoxy group by the hydroxyl group of the alcohol, followed by nucleophilic SN2 substitution to give the iodide (eq 1).

The MTPI reagent has been used to convert alcoholic hydroxyl groups into iodides in saturated and unsaturated aliphatic compounds (eq 2),4-9 carbohydrates,10,11 and nucleosides.13

A one-pot procedure involving in situ generation of MTPI from (PhO)3P and MeI through prolonged heating is generally convenient for reactions of saturated primary and sterically hindered alcohols.5,6 A two-step procedure6 using isolated MTPI and milder conditions is preferred for sensitive alcohols and in cases where elimination is expected, such as with all tertiary and many secondary alcohols. Both of these original procedures were conducted without solvent. Subsequent improvements include the use of polar solvents like DMF, which appear to promote the iodination reaction and allows it to proceed at rt in most cases.13c

Some carbon skeletal rearrangement is observed with highly hindered alcohols: t-pentyl iodide (6%) is formed in the conversion of neopentyl alcohol to neopentyl iodide;5 steroidal neopentyl alcohols undergo rearrangement followed by an elimination reaction.8

MTPI has been used for the synthesis9 of iodoallenes and iodoalkynes via SN2 and SN2 reactions; thus the primary alkynic alcohol prop-2-ynol gives either mainly iodoallene in DMF or mainly the iodoalkyne in CH2Cl2 (eq 3).9a

In the carbohydrate field, MTPI provides iodides from primary10 and secondary alcohols.10a,b,11 The latter alcohols generally give iodides with inverted configuration by SN2 reaction, but sometimes isomeric mixtures (resulting from isomerization by iodide ion) are obtained.11c,d Some structural rearrangements involving the participation of hydroxyl protecting groups are reported to occur in the preparation of iodides11a-d from hindered secondary alcohols; however, this work was later partly questioned in light of subsequent results.12

In the sugar moiety of nucleosides the primary 5-hydroxyl group is converted into iodide13a-f in high yield with MTPI, and the reaction can exhibit primary/secondary selectivity (eq 4).13c In some cases, with more polar solvents or in presence of an external base, cyclic N or O,5-anhydro derivatives, resulting from the attack of the base moiety on the 5-oxyphosphonium or 5-iodide intermediate, are obtained.13c-e,g.

Such cyclic anhydro intermediates, isolated under other reaction conditions, explains the retention of configuration by double inversion observed in the substitution reactions of secondary 2- or 3-hydroxyl groups (eq 5).13c,h

Reaction of MTPI with cis-vicinal glycols, such as nucleosides with secondary 2- and 3-hydroxy groups, provides phosphorane intermediates that yield a mixture of 2- and 3-phosphonates13c,h on hydrolysis. Linear g-diols can be cyclized by dehydration with MTPI to give C-glycoside precursors.13i

Alternative agents which convert various kinds of alcohols into iodides with good results include the Triphenylphosphine-additive reagent systems: I2,13f CI4,18 triiodoimidazole,12 NIS, etc.

Alcohol Dehydration and Alkyl Halide Dehydrohalogenation.

MTPI in HMPA at 75 °C selectively dehydrates secondary alcohols under mild conditions,14a-d leading predominantly to the more stable Saytzeff alkene with various (E/Z) stereoselectivity.14a,c Tertiary alcohols are unaffected under these conditions.

In eq 6, virtually stereospecific dehydration to the (E)-alkene is accompanied by transformation of the pyranyl ether group to the iodide, in high yield.14c

Conjugated polyenes are formed, either by dehydration of unsaturated alcohols or by dehydrohalogenation of the corresponding bromides, with MTPI in aprotic solvents such as HMPA15a,b and DMI.15c The suggested mechanism for this transformation involves initial conversion of the alcohol into the iodide with inversion, followed by dehydrohalogenation by either iodide ion or HMPA.

In a special case, leading to the formation of conjugated exocyclic double bond, primary alcohols undergo dehydration with MTPI in DMF under unusually mild conditions. This reaction provides a good method for a-methylenation of g-butyrolactones.16

Deoxygenation of Epoxides to Alkenes.

In combination with Boron Trifluoride Etherate, MTPI converts epoxides into alkenes in 75-99% yields,17 via syn elimination and with retention of stereochemistry. The reaction is conducted at rt in MeCN-C6H6 mixtures as solvent. An excess of both MTPI (10 molar equiv) and BF3 etherate (1-3 molar equiv) are generally required for satisfactory yields. This method compares favorably with another procedure using a Potassium Iodide-crown ether reagent system.

A modification of the MTPI reagent involves the use of Methyl Trifluoromethanesulfonate (methyl triflate) in place of MeI, thus providing the nonnucleophilic anion CF3SO3- instead of iodide.19 Treatment of aliphatic alcohols with MeP(OPh)3+ TfO- leads to symmetrical dialkyl ethers, whereas alkyl phenyl ethers are formed with sodium alcoholates.19b


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4. (a) Landauer, S. R.; Rydon, H. N. CI(L) 1951, 313. (b) Campbell, A.; Rydon, H. N. CI(L) 1951, 312. (c) Landauer, S. R.; Rydon, H. N. JCS 1953, 2224.
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16. Yamada, K.; Kato, M.; Hirata, Y. TL 1973, 2745.
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Jean-Robert Dormoy & Bertrand Castro

SANOFI Chimie, Gentilly, France



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