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A Sequential Homologation of Alkynes and Aldehydes for Chain Elongation with Optional 13 C‐Labeling
Author(s) -
Brunner Andreas,
Hintermann Lukas
Publication year - 2016
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201504248
Subject(s) - alkyne , aldehyde , chemistry , regioselectivity , reagent , ruthenium , azide , combinatorial chemistry , click chemistry , organic chemistry , catalysis
Terminal alkynes (RCCH) are homologated by a sequence of ruthenium‐catalyzed anti‐Markovnikov hydration of alkyne to aldehyde (RCH 2 CHO), followed by Bestmann–Ohira alkynylation of aldehyde to chain‐elongated alkyne (RCH 2 CCH). Inverting the sequence by starting from aldehyde brings about the reciprocal homologation of aldehydes instead. The use of 13 C‐labeled Bestmann–Ohira reagent (dimethyl ((1‐ 13 C)‐1‐diazo‐2‐oxopropyl)phosphonate) for alkynylation provides straightforward access to singly or, through additional homologation, multiply 13 C‐labeled alkynes. The labeled alkynes serve as synthetic platform for accessing a multitude of specifically 13 C‐labeled products. Terminal alkynes with one or two 13 C‐labels in the alkyne unit have been submitted to alkyne–azide click reactions; the copper‐catalyzed version (CuAAC) was found to display a regioselectivity of >50 000:1 for the 1,4‐ over the 1,5‐triazine isomer, as shown analytically by 13 C NMR spectroscopy.