New routes to beta-cycloalkylalanine derivatives using serine-derived organozinc reagents.
Two distinct routes to beta-cycloalkylalanine derivatives have been developed. The first route employs the reaction of the iodoalanine-derived zinc-copper reagent 2 with cycloalk-1-en-3-yl phosphates, and the second uses the palladium-catalysed coupling of the iodoalanine-derived zinc reagent 1 with cycloalkenyl triflates; in each case, catalytic hydrogenation of the unsaturated product leads to the protected beta-cycloalkylalanine. The latter route allows access to a range of cycloalkyl derivatives, with ring sizes of 5-8. beta-(1-Methyl-1-cyclohexyl)alanine may be prepared using reaction of the zinc-copper reagent 2 with 3-methyl-2-cyclohexenyl chloride, followed by hydrogenation. The corresponding cyclopentyl derivative may be prepared by reaction of the same zinc-copper reagent 2 with diethyl geranylphosphate, followed by ring-closing metathesis and hydrogenation.
Carrillo-Marquez
Tomas
T
Department of Chemistry, Dainton Building, University of Sheffield, Brook Hill, Sheffield, UKS3 7HF.
Caggiano
Lorenzo
L
Jackson
Richard F W
RF
Grabowska
Urszula
U
Rae
Alastair
A
Tozer
Matthew J
MJ
D000409:Alanine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D003516:Cycloparaffins / Q000138:chemical synthesis* / Q000737:chemistry*; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000737:chemistry*; D012694:Serine / Q000737:chemistry*; D015032:Zinc / Q000737:chemistry*
D003516:Cycloparaffins; D009942:Organometallic Compounds; D012694:Serine; D015032:Zinc; D000409:Alanine