The Vespiary

Reduction of Carbonyl Function to a Methyl Group
Gan B. Bajracharya,a Tsutomu Nogami,a Tienan Jin,a Kumiko Matsuda,a Vladimir Gevorgyan,b
Yoshinori Yamamoto*a

Synthesis 2, 308, 2004

DOI:

10.1055/s-2003-44356 (http://dx.doi.org/10.1055/s%2D2003%2D44356)

(https://www.thevespiary.org/rhodium/Rhodium/hive/hiveboard/picproxie_imgs/pdf.gif)

Abstract: A direct exhaustive reduction of aliphatic carbonyl functions (aldehydes, acyl chlorides, esters and carboxylic acids) to a methyl group by triethylsilane (Et3SiH) in the presence of catalytic amount of tris(pentafluorophenyl)borane [B(C6F5)3] is described. Aromatic carbonyl functions could undergo partial reduction to the corresponding TES-protected benzylic alcohols


...Excerp this methodology provides an effective reduction of aliphatic carboxyl group into the corresponding hydrocarbon in very high yield.

Note _{a search was made looking for 2 308 2004 on the TFSE to avoid re-posting}

Did I get that right: -COOH to CH3 - wouldn't this mean phenylalanine->phenyl(2)aminopropane in a rather sophisticated high-tech synthesis (using WIERD reagents..  :) ), but with 90%+ yields?

Dang, that would bee a nice find...

Greetz A

A very similar procedure was published in 2001, using the very same reagents to pull it off:

Post 194986 (https://www.thevespiary.org/talk/index.php?topic=12508.msg19498600#msg19498600)

(Rhodium: "First published direct reduction of COOH to CH3", Serious Chemistry)

Yes, the method can likely be used to reduce phenylalanine to amphetamine, but you still need to protect the nitrogen, IMHO.

Rhodium you are correct to see the similarities , it's because one of the same co-authors in the 2001 study,Yamamoto,Y, is also a co author in this study. However one  distinction is made by this current study.........

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In our previously reported procedure,11 a use of hydrofluoric acid was essential in the work-up process for these transformations. Since hydrofluoric acid is highly poisonous and one of the most hazardous chemicals, we sought a milder, safer and equally efficient condition to utilize our methodology for practical synthetic purpose. We found that, use of conc. H2SO4 and NH4F is equally effective, quick, safer and milder than use of hydrofluoric acid (see Procedure 1 for details).

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Ref.

11. Journal of Organic Chemistry 66, 1672-1675 (2001)
                                Gevorgyan, V.; Rubin, M.; Liu, J.-X.; Yamamoto, Y.

The same authors published a study prior to their JOC article, using the system for the reduction of alcohols and ethers. Only primary alcohols and ethers were found to give the hydrocarbons; the secondary and tertiary alcohols gave the corresponding silyl ethers. Reference 1(c) from the following article, dealing with the reduction of secondary benzyl alcohols with triethylsilane/boron trifluoride, may be worth looking up.


A novel reduction of alcohols and ethers with a HSiEt₃/catalytic B(C₆F₅)₃ system
Vladimir Gevorgyan, Jian-Xiu Liu, Michael Rubin, Sharonda Benson and Yoshinori Yamamoto
Tetrahedron Letters, 40 (1999), 8919-8922

Abstract
The primary alcohols 1a-d and ethers 4a-b were effectively reduced into the corresponding hydrocarbons 2 by HSiEt₃ in the presence of catalytic amounts of B(C₆F₅)₃. The secondary alkyl ethers 4g,h underwent cleavage and/or reduction under similar reaction conditions to produce either the silyl ether 3k or the corresponding alcohol 5b upon subsequent deprotection with TBAF. The secondary alcohols (1g,h) and tertiary alcohol 1i, as well as tertiary alkyl ether 4i, did not react with the HSiEt₃/(B(C₆F₅)₃ reducing reagent at all. The following relative reactivity order of substrates was found: primary>>secondary>tertiary. The methyl aryl ethers 4c-e and alkyl aryl ether 4f were smoothly deprotected to give the corresponding silyl ethers 3b,h-j in nearly quantitative isolated yields.

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