Re-constructing Alcohols

Figure 1. The Iridium Catalyst used in the study. Taken from Ref. [1].

The impressive work of the week is from Professor M.J. Krische’s group, for which some of their works in Redox Coupling have been covered before in my article ‘Atom Economy’ [1]. Published in Nature Chemistry, they have succeeded in coupling methanol (CH3OH) to the structurally intriguing allene to afford a number of higher alcohols [2]. They have used similar iridium catalysts to carry out a number of carbon-carbon coupling reactions recently [3].


Figure 2. Ir-catalysed C-C coupling of methanol to allene. Taken from Ref. [1].

Methanol (CH3OH), the simplest alcohol (alkanol) of all, is indeed a very useful precursor in many industrial processes, and the best examples are the Monsanto process and the Cativa process. In most circumstances, the reactive portion of a methanol molecule is AT the oxygen end. Krische et.al. has demonstrated that the carbon end can indeed become reactive and carry out a carbon-carbon coupling with an allene under Iridium catalysis. The significance of this is two fold. The coupling reaction leads to the generation of a quaternary carbon center, and more importantly, the fact that methanol reacts at the carbon end represents a C-H activation process of an usually ‘inert’ methanol molecule. This latter significance is clearly something worth looking further into. Of course, this reaction is atom-economical.


Figure 3. The proposed mechanism. Taken from Ref. [1].

The catalytic cycle [1] commences when methanol enters and displaces the allyl ligand in the Iridium pre-catalyst. Through the formation of the O-Ir bond, a dehydrogenation occurs and the bound methanol is converted into formaldehyde. The formaldehyde is detached from the catalyst at this stage, and it will ‘come back’ in the later part of catalysis. The vacant site created by the departure of formaldehyde is taken up by the allene substrate, which forms an allylic iridium intermediate (via η-3 interaction). It is at this stage the formaldehyde comes back to the catalytic cycle, and the addition of the nucleophilic iridium intermediate to formaldehyde affords the precursor of the final product. The product is liberated from the catalytic cycle by methanol.

The coverage from the RSC Chemistry World Website gives further insights and perspectives from that of Professor Krische [4].

http://www.rsc.org/chemistryworld/News/2011/February/27021101.asp

Note Added: on 4th March 2011, a new publication from the same group appears on Angew. Chemie. Int. Ed., using a similar Iridium Catalyst.

Enantioselective Iridium-Catalyzed Vinylogous Reformatsky-Aldol
Reaction from the Alcohol Oxidation Level: Linear Regioselectivity by
Way of Carbon-Bound Enolates
Abbas Hassan, Jason R. Zbieg, and Michael J. Krische
Angew. Chemie Int. Ed. 2011
DOI : 10.1002/anie.201100646


References:

1. http://emockscience.blogspot.com/2010/06/c-6-carbons-12-carbons-18-carbons-waste.html

2. Iridium-catalysed direct C–C coupling of methanol and allenes
Joseph Moran, Angelika Preetz, Ryan A. Mesch and Michael J. Krische
Nature Chemistry
Published online 27 February 2011
DOI: 10.1038/NCHEM.1001

3. For recent examples of the use of similar Ir catalysts in C-C coupling reactions, see:

(a) Synthesis of the Cytotrienin A Core via Metal Catalyzed C-C Coupling
Michael Rössle, David J. Del Valle, and Michael J. Krische, Org. Lett. 2011, ASAP.
DOI: 10.1021/ol200160p

(b) Total Synthesis of (+)-Roxaticin via C-C Bond Forming Transfer
Hydrogenation: A Departure from Stoichiometric Chiral Reagents, Auxiliaries,
and Premetalated Nucleophiles in Polyketide Construction
Soo Bong Han, Abbas Hassan, In Su Kim, and Michael J. Krische
J. Am. Chem. Soc., 2010, 132 (44), 15559.

(c) Iridium-Catalyzed anti-Diastereo- and Enantioselective Carbonyl (Trimethylsilyl)allylation from the Alcohol or Aldehyde Oxidation Level
Soo Bong Han, Xin Gao, and Michael J. Krische
J. Am. Chem.Soc. 2010, 132, 9153.

(d) anti-Diastereo- and Enantioselective Carbonyl (Hydroxymethyl)allylation from the Alcohol or Aldehyde Oxidation Level: Allyl Carbonates as Allylmetal Surrogates
Yong Jian Zhang, Jin Haek Yang, Sang Hoon Kim, Michael J. Krische
J. Am. Chem. Soc. 2010, 132, 4562.

(e) Iridium-Catalyzed Hydrohydroxyalkylation of Butadiene: Carbonyl Crotylation
Jason R. Zbieg, Takeo Fukuzumi and Michael J. Krische
Advanced Synthesis and Catalysis 2010, 352, 13-15, 2416.

(f) 1,n-Glycols as Dialdehyde Equivalents in Iridium-Catalyzed Enantioselective Carbonyl Allylation and Iterative Two-Directional Assembly of 1,3-Polyols†
Yu Lu, In Su Kim, Abbas Hassan, David J. Del Valle and Michael J. Krische
Angew. Chem. Int. Ed. 2009, 48, 27, 5018.

4. http://www.rsc.org/chemistryworld/News/2011/February/27021101.asp