Dehydroxylative Cyanation of Alcohols Promoted by Triphenyphosphine/1,2-Diiodoethane

Abstract

A Ph₃P/ICH₂CH₂I-promoted dehydroxylative cyanation of alcohols has been developed. In contrast to previous dehydroxylative cyanation methods that can suffer from several limitations, such as the use of transition metals or moisture-sensitive Lewis acids, this protocol features convenient operations, mild reaction conditions, and the use of cheap and widely available reagents.

Key words

dehydroxylation - alcohols - cyanation - hydroxyl group - nucleophilic substitution

Publication History

Received: 03 January 2023

Accepted after revision: 06 February 2023

Accepted Manuscript online:
06 February 2023

Article published online:
28 February 2023

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• 24 Dehydroxylative Cyanation of Alcohols: General Procedure A 25 mL tube was charged with Ph₃P (0.6 mmol, 1.2 equiv), ICH₂CH₂I (0.6 mmol, 1.2 equiv), the appropriate alcohol 1 (0.5 mmol, 1 equiv), and DMF (5 mL) under N₂. When the solid had completely dissolved, TMSCN (4.0 equiv) and K₂CO₃ (3.0 equiv) were added under N₂ and the mixture was stirred at r.t. for 12 h. Sat. aq brine was added and the crude organic product was extracted with CH₂Cl₂. The combined organic phase was dried (Na₂SO₄), filtered, and concentrated under reduced pressure. The residue was purified by flash column chromatography (silica gel, pentane–EtOAc) Biphenyl-4-ylacetonitrile (3a) White solid; yield: 94 mg (97%). ¹H NMR (400 MHz, CDCl₃): δ = 7.65–7.53 (m, 4 H), 7.50–7.33 (m, 5 H), 3.80 (s, 2 H). ¹³C NMR (101 MHz, CDCl₃): δ = 141.2, 140.2, 128.9, 128.8, 128.4, 127.9, 127.7, 127.1, 117.8, 23.3. LRMS (EI): m/z [M]⁺ calcd for C₁₄H₁₁N: 193.1; found: 193.1.