Direct Conversion of Internal Alkynes into α‐Iodoenones: One‐Step Collaborative Iodination and Oxidation

Abstract

Ther eactiono fa ni nternal alkyne with 2,6-dichloropyridine N-oxide,anucleophilic oxidant, and electrophilic N-iodosuccinimide (NIS)s imultaneously enables the direct access to versatile a-iodoenones.E lectronically biased internala lkynes undergo the one-stept ransformation with excellent regioselectivities andw ith practical Z/E ratios.I n comparison to the relatedo xidative gold catalysis using pyridine N-oxides,t his reaction employs NIS as the stoichiometric ynophile instead of the soft acidic noble metal catalyst and affords products featuring an additional versatileC À Ib ond. Similar strategies for replacing ynophilic cationic gold(I) complexes in oxidative gold catalysis with likewise ynophilic stoichiometric electrophiles would enable the development of new synthetic methods.Keywords: alkynes;e nones; iodination;o xidation; pyridine N-oxides a-Iodoenones possess an electrophilic enone moiety susceptible to either 1,4-or 1,2-addition andaversatile C À Ib ondf or transitionm etal catalysis.A ss uch, they are valuables tructures in organic synthesis. Theirs yntheses have been achieved mostly via iodination of functional substrates such as enones, [1] a-silyl/stannyla,b-unsaturated ketones, [2] propargylic alcohols [3] and their ester counterparts, [4] and occasionally via oxidation of iodinated allylica lcohols.[5] Therei ss eldom an approacht hat accomplishesb otho xidation and iodination in ac ollaborative fashion in one step from substrates with lesser degreeso fo xidation/functionalization.[6] Herein, we report an implementation of this approachu sing minimally functionalized internal alkyne substrates. Fort he past several years our group [7] and others [8] have reported the applications of an oxidative gold catalysis strategy in the development of versatiles ynthetic methods. As shown in Approach Ao f Scheme 1A, the coordination of as oft Lewis acidic gold catalyst to aC Ct riple bond triggers the attack of an ucleophilic oxidanta ti ts p bond. Thei nitial adduct can undergo fragmentation of the inherently weak O À Zb ond to offer expedient access to versatile a-oxo gold carbenes;a lternatively,i tm ay proceed to functionalized productsw ithout the carbene intermediacy in the presenceo famore facile reactionp athway.D ue to the catalytic nature of this chemistry,t he in situ generated Au À Cb ond in this class of reactions Scheme1.Replacingg old catalysts with stoichiometric electrophiles in the oxidationo fa lkynes by nucleophilic oxidants.

A Gold(I)‐Catalyzed Oxidative Rearrangement of Heterocycle‐Derived 1,3‐Enynes Provides an Efficient and Selective Route to Divinyl Ketones

“…The regioselective oxidation of internal, nonsymmetrical alkynes was first reported by Zhang and co‐workers . Interestingly, similar transformations were realized in the absence of gold catalyzed by HBF 4 ⋅OEt 2 and N ‐iodosuccinimide . As a result of our interest in the chemistry of heterocycle‐derived triflates and phosphates as key intermediates in the synthesis of natural compounds, we have previously demonstrated that the gold(I)‐catalyzed cyclization reaction of N ‐ tert ‐butoxycarbonyl (Boc) protected 6‐alkynyl‐3,4‐dihydro‐2 H ‐pyridines affords synthetically useful vinylogous amides (Scheme , b) .…”

“…Compound 2g can then arise from a deprotonative Grob‐type fragmentation of B (Scheme ) followed by fast deprotioauration of C , the driving force of the process being the formation of a highly conjugated compound …”

Direct Synthesis of α-Iodoenones by IPy2BF4-Promoted Rearrangement of Propargylic Esters

“…14 In the past decade, some authors have described more efficient and versatile methods for the synthesis of -iodoenones based in the rearrangement of propargylic alcohol derivatives, that improve the limitations from the use of enone derivatives as precursors. 15 Interestingly, apart from some studies limited to tertiary propargylic alcohols using iodine and an oxidant, 16 and a recent example through oxidation of internal alkynes in the presence of NIS, 17 most general methods require the employment of at least one metal catalytic species to promote the reaction. 3c, 8, 18 Considering this, we describe herein the rearrangement reaction of propargylic alcohol derivatives promoted by reactive iodonium ion, and its use as a new, versatile and general metal-free synthetic method of -iodoenones.…”