Experimental Studies on the Selective β-C–H Halogenation of Enones

Abstract

Here we describe the realization of a one-pot protocol for the β-C-H halogenation of cyclic enones via umpolung of the β-carbon. The developed method includes hydrazone formation and selective β-halogenation (bromination, chlorination) with N-bromosuccinimide and Palau'chlor (2-chloro-1,3-bis(methoxycarbonyl)guanidine) followed by hydrolysis of the hydrazone moiety. Using the optimized conditions, we were able to effectively β-brominate and β-chlorinate for the first time cyclic enones with different substitution patterns and various functional groups in one flask, whereas previous methods for this transformation required several steps. Additionally, the utility of the method was demonstrated in a short synthesis of the core structure of the Aspidosperma alkaloid jerantinine E.

Vinylation of a Secondary Amine Core with Calcium Carbide for Efficient Post-Modification and Access to Polymeric Materials

“…The Clemo-Perkin method [ 18 ] and dehydrohalogenation in the presence of phase transfer catalyst [ 19 ] lead to N -vinyl derivatives of indoles [ 20 ], carbazoles [ 21 ], imidazoles [ 22 ], pyrazoles, triazoles, or tetrazoles [ 23 ] and nitrogenous bases [ 24 ]. Several other transformations leading to N -vinyl derivatives, such as dehydrogenation [ 25 ], ethylene insertion [ 26 ], and amine/aldehyde condensation could be also mentioned [ 27 ].…”

A One Pot Synthesis of Dehydrohedione (DHH) from a Hedione® Precursor

“…The one-pot transformation of 5a into the b-bromo derivative 5c (BocNHNH 2 , ClCH 2 CH 2 Cl, 85°C, NBS, Et 3 N, Amberlyst-15, [87] ) failed 20 The situation did not improve under stepwise conditions 21 , while the known 4-bromo cyclopent-2-enone 5e [91] [92] also failed to give the desired conjugate addition, as 5l was rather isolated (dimethyl malonate, MeONa, MeOH, 40% yield) 22 Further demethoxycarbonylation (H 2 O, NMP, 155°, 97% yield) afforded 5m, a precursor of cis-11a [108 -111] (MeOH, 10% Pd/C, H 2 , 98% yield, 90:10 mixture of stereoisomers), which exhibits a typical floral, jasmine, green, elegant, and natural scent (for complementary analyses, see Supporting information). The unreported a'-substituted cyclopentenones 5i, 5j were prepared from 5a either quantitatively by equimolar addition of NBS in MeCN, catalyzed by TMSOTf at 20°C, [112]23 or by oxidation with 2.0 molequiv.…”

Recent Update on Transition Metal‐Free C(sp2)−H Bond Halogenation in (Hetero) Arenes

“…[ 2 ] Different functionalities have been incorporated via ‘C‐halogenated’ positions giving rise to a broad range of interesting products [3] . Some interesting C−H bond halogenation have been observed in different molecules [4–7] . Various approaches have been made to insert suitable halogen regioselectively at desired position of a particular organic moiety with high enantioselectivity [1c] .…”

“…[3] Some interesting CÀ H bond halogenation have been observed in different molecules. [4][5][6][7] Various approaches have been made to insert suitable halogen regioselectively at desired position of a particular organic moiety with high enantioselectivity. [1c] Halogenated derivatives have a good reputation in the field of synthetic chemistry as useful intermediates for various transformations.…”