A Sequential Homologation of Alkynes and Aldehydes for Chain Elongation with Optional ¹³C‐Labeling

Abstract

Terminal alkynes (RCCH) are homologated by a sequence of ruthenium-catalyzed anti-Markovnikov hydration of alkyne to aldehyde (RCH2CHO), followed by Bestmann-Ohira alkynylation of aldehyde to chain-elongated alkyne (RCH2CCH). 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.

Room-temperature chemical synthesis of C2

“…After 72 h, the formation of 15 and 16 was confirmed by APCI-MS analysis of the residue in Flask B. We then performed a 13 C-labeling experiment using 1b-13 C β , which was synthesized from H 3 13 C-I in eight steps 28,29 . Treatment of 1b-13 C β (99% 13 C) with Bu 4 NF in the presence of 14 in CH 2 Cl 2 gave a mixture of 15-13 C α and 15-13 C β , suggesting that C 2 is generated before the O-ethynyl bond-forming reaction with 14 (Fig.…”

Configurational Assignment of ‘Cryptochiral’ 10‐Hydroxystearic Acid Through an Asymmetric Catalytic Synthesis

“…[24 ‐ 26] To access aldehyde 5 , we planned to showcase Ru‐catalyzed anti‐Markovnikov hydration of terminal alkynes as a versatile synthetic method that converts readily storable alkynes by microwave‐based hydration to the corresponding aldehydes within minutes. [27f][27h] Precursor alkyne 7 results via bromination–elimination from alkenoic acid 8 . [29][30] Alternatively, ozonolysis of homologous alkenoic acid 9 will give the same aldehyde 5 with shortening of the carbon chain.…”

“… For catalytic anti‐Markovnikov hydration methodology [see Ref. 27]; for catalytic anti‐Markovnikov hydration in synthesis [see Ref. [28].…”

Synthesis of End-Functionalized Poly(norbornenes) and Poly(ethylidene norbornenes) Using a Pd(II) Catalyst in Combination with Chain Transfer Agents

“…Condensation Reaction with 2,4-Dinitrophenylhydrazine. 16 The aldehyde end-capped PENB (M n = 4.9K, Table 3, entry 4, 98.0 mg, 0.02 mmol, 1.0 equiv) was dissolved in CH 2 Cl 2 (3.0 mL). To this solution were added p-TsOH•H 2 O (3.8 mg, 0.1 equiv) and 2,4dinitrophenylhydrazine (4.2 mg, 0.021 mmol, 1.05 equiv), and the mixture was stirred for 24 h at 25 °C.…”