Hydrogen Borrowing Catalysis with Secondary Alcohols: A New Route for the Generation of β-Branched Carbonyl Compounds.
A hydrogen borrowing reaction employing secondary alcohols and Ph* (Me5C6) ketones to give β-branched carbonyl products is described (21 examples). This new C-C bond forming process requires low loadings of [Cp*IrCl2]2, relatively low temperatures, and up to 2.0 equiv of the secondary alcohol. Substrate-induced diastereoselectivity was observed, and this represents the first example of a diastereoselective enolate hydrogen borrowing alkylation. By utilizing the Ph* group, the β-branched products could be straightforwardly cleaved to the corresponding esters or amides using a retro-Friedel-Crafts reaction. Finally, this protocol was applied to the synthesis of fragrance compound (±)-3-methyl-5-phenylpentanol.
Department of Chemistry, Chemical Research Laboratory, University of Oxford , Oxford, OX1 3TA, United Kingdom.
Wasim M
WM
Akhtar
Department of Chemistry, Chemical Research Laboratory, University of Oxford , Oxford, OX1 3TA, United Kingdom.
Choon Boon
CB
Cheong
Department of Chemistry, Chemical Research Laboratory, University of Oxford , Oxford, OX1 3TA, United Kingdom.
James R
0000-0002-4966-0419
JR
Frost
Department of Chemistry, Chemical Research Laboratory, University of Oxford , Oxford, OX1 3TA, United Kingdom.
Kirsten E
KE
Christensen
GlaxoSmithKline, Medicines Research Centre, Stevenage, SG1 2NY, United Kingdom.
Neil G
NG
Stevenson
Department of Chemistry, Chemical Research Laboratory, University of Oxford , Oxford, OX1 3TA, United Kingdom.
Timothy J
0000-0001-7088-6626
TJ
Donohoe