The Vespiary

The Hive => Novel Discourse => Topic started by: Lilienthal on October 20, 2001, 12:53:00 AM

Title: P2P from benzylchloride / LiAc / Li
Post by: Lilienthal on October 20, 2001, 12:53:00 AM

Synlett 459 (1995): A direct access to ketones from litium carboxylates via the sonochemical Barbier reaction:

R-COOLi + R'-Cl + Li^{° __}> R-CO-R' (in THF, rt, 20 min, ultrasonication)

With lithium acetate and benzylchloride you should get P2P in good yields.

They use 1 eq R-COOLi, 1.5 eq R'-Cl, and 3 eq lithium metal. I know, lithium is a bit expensive, but maybe it's a nice synthesis for substituted P2P's on a small scale.

Title: Re: P2P from benzylchloride / LiAc / Li
Post by: jim on October 20, 2001, 02:51:00 PM

Are you sure that this isn't a SN2 pathway, i.e. a backside attack mechanism and therefore impossible for a phenyl group?

Title: Re: P2P from benzylchloride / LiAc / Li
Post by: Lilienthal on October 21, 2001, 11:16:00 AM

? It proceeds through in-situ lithiation of the alkyl chloride. This alkyl-lithium (benzyl-lithium) nucleophile attacks the carbonyl-C. Further reaction of the product to the tertiary alcohols is prevented by using the carboxylate salt.

Taking the low atomic weight of lithium (7!) and the use of Li of low purity (< 98% Li, 2% Na) into account the reagent is not that expensive!

Title: Re: P2P from benzylchloride / LiAc / Li
Post by: PolytheneSam on October 22, 2001, 06:00:00 PM

See

Patent US4936966 (http://l2.espacenet.com/dips/viewer?PN=US4936966&CY=gb&LG=en&DB=EPD)

.  If you used a mixture of benzyl chloride and excess methyl chloride (or other halide) maybe you could get a good yield of P2P from the benzyl chloride.  Also see

Patent US4629541 (http://l2.espacenet.com/dips/viewer?PN=US4629541&CY=gb&LG=en&DB=EPD)

.

Title: Re: P2P from benzylchloride / LiAc / Li
Post by: foxy2 on October 22, 2001, 07:09:00 PM

Cerium(III) chloride remarkably increases the rates of formation and yields of ketones in the reaction of lithium carboxylates with organolithiums
Tetrahedron Letters 35(2), 203-206 (1994)

Abstract
The presence of CeCl₃ greatly increases the yield of ketones in the reaction of organolithiums with lithium carboxylates. The CeCl₃ suppresses the enolization of the lithium carboxylate and the formation of tertiary alcohols. One reason for the latter effect is an increase in the rate of addition of the organometallic to the lithium carboxylate in the presence of CeCl₃.

Title: PAA + 2 MeLi + 2 CeCl3 -> P2P (62%)
Post by: Rhodium on May 17, 2004, 05:28:00 PM

Cerium(III) Chloride Remarkably Increases the Rates of Formation and Yields of Ketones in The Reaction of Lithium Carboxylates with Organolithiums
Yoonmo Ahn and Theodore Cohen

Tetrahedron Letters 35(2), 203-206 (1994) (https://www.thevespiary.org/rhodium/Rhodium/pdf/p2p.paa-meli-cecl3.pdf)

(https://www.thevespiary.org/rhodium/Rhodium/pdf/p2p.paa-meli-cecl3.pdf)

Abstract
The presence of CeCl₃ greatly increases the yield of ketones in the reaction of organolithiums with lithium carboxylates. The Ce³⁺ suppresses the enolization of the lithium carboxylate, previously unrecognized as a competing reaction except in special cases, and the formation of tertiary alcohols. One of the reasons for the latter effect is a surprising increase in the rate of addition of the organometallic to the lithium carboxylate in the presence of Ce³⁺.

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Experimental
Methyl lithium (1 equivalent) is added to a solution of phenylacetic acid in anhydrous THF at -78°C and stirred for 15 min to form a suspension of lithium phenylacetate. A suspension of CeCl₃ (2 Eq.) in THF* at -78°C is added to the solution and the resulting mixture stirred for 30 min at -78°C.  Methyl lithium (1 equivalent) is added dropwise and the mixture stirred for 16 hours, after which time the reaction was quenched by the dropwise addition of 5% aqueous HCl at -78°C. Standard workup gave phenyl-2-propanone in 62% (isolated) yield, with negligible formation of any tertiary alcohol and the remainder being mostly unreacted starting material.

^{* CeCl₃·7H₂O (Aldrich) is dried by stirring the material for two hours in a flask at 180°C/0.4 mmHg pressure. A suspension in anhydrous THF is stirred at ambient temperature for at least 3 h before use.}

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