The J ulia– K ocienski Olefination

Abstract

The Julia–Kocienski olefination is a direct connective synthesis of alkenes via the addition of metalated aryl alkyl sulfones to carbonyl compounds. The activating aromatic group associated with the sulfone must possess electrophilic character, and alkene formation occurs via β‐alkoxy sulfone formation, transfer of the aryl group from sulfur to oxygen via a Smiles rearrangement, and then elimination of sulfur dioxide and an aryloxide anion from the resulting β‐aryloxy sulfinate anion. The olefination process itself and the methods used to prepare the requisite sulfone substrates are tolerant of a wide variety of functional groups, and a variety of alkene targets can be prepared. Stereoselectivity is dependent on the nature of the sulfone, the carbonyl compound, the activating aryl moiety, and the reaction conditions. This chapter describes theoretical and operational aspects of the Julia–Kocienski olefination such that the reader will be able to obtain optimal results in his/her own research. A detailed mechanistic overview is included to account for the factors that influence stereoselectivity and yield. Methods for introducing sulfone activators into fragments of interest, best practices for generating sulfone anions, and optimal strategies for targeting different classes of alkene targets are discussed. Functional group compatibilities, reaction variants, and a comparison to other methods of alkene synthesis are also presented. Tabular surveys are organized according to type of alkene synthesized, with an emphasis on the degree of substitution and the level of conjugation about the newly formed double bond. The literature is covered from the initial disclosure of the Julia–Kocienski olefination in 1991 to the first quarter of 2016.

Synthesis of non-racemic 4-nitro-2-sulfonylbutan-1-ones via Ni(II)-catalyzed asymmetric Michael reaction of β-ketosulfones

“…Sulfones are widely used in organic synthesis, particularly, in various reactions of C–C and C=C-bond formation [1–4]. The use of sulfones in Julia–Kocienski [1] and Ramberg–Bäcklund reactions [2] made this class of compounds frequently used in the synthesis of organic fine chemicals and natural compounds.…”

“…Sulfones are widely used in organic synthesis, particularly, in various reactions of C–C and C=C-bond formation [1–4]. The use of sulfones in Julia–Kocienski [1] and Ramberg–Bäcklund reactions [2] made this class of compounds frequently used in the synthesis of organic fine chemicals and natural compounds. In addition to using the sulfonyl group as an auxiliary, it is also included in some chiral bioactive molecules, such as remikiren ( 1 , renin inhibitor for the treatment of hypertension) [5–6], eletriptan ( 2 , Relpax ® , serotonin 5-HT 1 receptor agonist for the treatment of migraine) [7], and apremilast ( 3 , Otezla ® , inhibitor of the PDE4 for the treatment of certain types of psoriasis and psoriatic arthritis) [8] (Fig.…”

C–H‐Alkenylation of Arenes in a One‐Pot VNS – Julia‐Kocienski Reaction

“…A VNS reaction of a chloromethyl heteroaryl sulfone would result in the formation of a nitrobenzyl carbanion 2 containing a heteroaryl sulfonyl group (EWG = HetSO 2 , Het = heteroaryl) at the anionic centre. With an appropriate heteroaryl moiety, such as benzothiazolyl (BT), 2‐pyrimidynyl (PY) or phenyltetrazolyl (PT), such anion would be an appropriate partner for a Julia‐Kocienski (J‐K) olefination process, assuming that it is capable of undergoing addition to a carbonyl compound, followed by a heterocyclic moiety transfer from sulfur to oxygen and subsequent SO 2 and HetO – elimination. Overall, such a tandem process would be a means of introducing an alkenyl moiety into an aromatic ring directly at the position occupied by hydrogen, in a transition metal‐free reaction (Scheme b).…”

Σύνθεση Φυσικών Τερπενίων Ή/Και Αναλόγων Τους Με Πιθανή Βιολογική Δράση

“…87 Αν και όλες οι προαναφερόμενες ολεφινοποιήσεις μπορεί να οδηγούν τελικά στο ίδιο αλκένιο, μία μέθοδος πρέπει να προτιμάται σε κάθε περίπτωση έναντι κάποιας άλλης για λόγους απόδοσης, στερεοεκλεκτικότητας, ευκολίας εφαρμογής και συμβατότητας της μεθόδου στο εν λόγω υπόστρωμα. 88…”

“…186,187 Είναι ευρέως γνωστό πως η στερεοεκλεκτικότητα των τριυποκατεστημένων αλκενίων που παρασκευάζονται μέσω της αντίδρασης Julia-Kocienski είναι μέτρια. 88 Αν και στη βιβλιογραφία υπάρχουν μερικά παραδείγματα όπου μεθυλοδιαλκυλοαλκένια παρασκευάζονται με καλή Ε-διαστερεοεκλεκτικότητα, 188-193. ωστόσο αυτά τα αποτελέσματα δεν μπορούν να υποστηρίξουν την εφαρμογή συγκεκριμένων κανόνων όσον αφορά τη βάση ή/και τον διαλύτη που χρησιμοποιούνται σε κάθε αντίδραση. Επίσης, υπάρχουν σίγουρα και άλλα δομικά χαρακτηριστικά που διέπουν τα αντιδρώντα υποστρώματα και τα οποία μπορεί να διαδραματίζουν κομβικό ρόλο στο αποτέλεσμα κάθε αντίδρασης.…”