& Vinyl Carbenoids Carbolithiation of Chloro-Substituted Alkynes: A New Access to Vinyl Carbenoids Rudy Lhermet, [a] Maha Ahmad, [a] Catherine FressignØ, [a] Bernard Silvi, [b] Muriel Durandetti,* [a] and Jacques Maddaluno* [a] Abstract: The intramolecular carbolithiation of a series of chloro-substituted alkynes leads to exocyclic alkylidene carbenoids of which both nucleophilic and electrophilic characters can be drove. A sole stereoselective 5-exo-dig addition takes place, probably because of a strong and persisting Li–Cl interaction arising before the transition state. Carbenoids are versatile reagents that juxtapose a metal and an electronegative element (generally an halogen) on the same carbon atom. [1] Because they cumulate a nucleophilic and an electrophilic character, these have found many applica- tions for the C C bond formation in various fields of organic chemistry, from natural product synthesis, [2] heterocyclic chemistry, [3] C H activation [4] to cyclopropanation, [1a, 5d, 6c] or di- verse homologation reactions. [6a–b] The metals implied in this chemistry go from lithium, [1b,c, 5] to magnesium, [7] zinc, [6] iron, [8] rhodium, [9] gold, [10] chromium. [11] The sp 3 lithium-based carbenoids, first studied by Kçbrich in the 1960s, [12] are configurationally stable at low temperature and have found elegant applications in stereoselective synthe- sis. [13] The lithium sp 2 analogues received attention later on, and it was shown that they exhibit a similar chameleon-like be- havior, at the exception of the very limited cyclopropanation pathway. In his review, Braun underlines that three routes to vinylidene carbenoids have been identified, which are deproto- nation, halogen–lithium exchange or transmetallation. [1b] We describe here a new access to this family of reagents based on an intramolecular carbolithiation reaction, giving precursors of five-membered heterocycles of fine synthetic value. [14] The carbometallation of simple internal alkynes affords tri- substituted vinylmetals, which can in turn trap an electrophile and yield tetrasubstituted olefins. [15] Generating vinylidene car- benoids by such a transformation requires that the electroneg- ative element juxtaposed to the lithium is borne directly by the C  C triple bond. [14c] Such a case is met seldom [15j] since the starting substrate has to combine a highly reactive nucleo- philic center and a fragile and little activated electrophile, in- compatible a priori. The stereocontrol of the newly created double bond is another standing problem. In general, the car- bolithiations of alkynes are known to occur in a syn fashion. [16] Our own studies revealed that, at least in one case, the lithium cation can be steered by a proximal coordination. [17] We focused this study on chloroalkynes, precursors of can- onical 1-halo-1-alkenyllithiums (Table 1). Chlorine was the halogen of choice since chloroalkynes are easily synthetized, while fluoroalkynes are known to be unsta- ble and even explosive compounds. [18] On the other hand, bro- moalkynes (and iodoalkynes) are more sensitive to halogen– lithium exchanges. Substrates 1 were prepared by chlorination of the corre- sponding lithium acetylides [19] by TsCl, [20a] CCl 4 [20b] or NCS. [19b] Treating 1 with nBuli (method A) or PhLi (method B) triggered the expected I–Li exchange, and the resulting aryllithium un- derwent rapid carbolithiation to afford the 5-exo-dig products 2 with total regio-, stereo- and chemoselectivity (Table 1). While nBuLi triggers some chlorine–lithium exchange (5–25 %, Table 1), PhLi affords, in all cases, a total conversion. The scope of this method is relatively large since propargylic ethers and “amides”, electron-withdrawing or donating substituents on the aromatic as well as a pyridine nucleus are tolerated. In all examples considered, the NOESY suggested that 2 are exclu- sively E (confirmed for 2c by X-rays analysis) and result from the anti addition of the aryllithium on the triple bond. Note that if the conversions are generally good (see spectra in the Supporting Information), the isolated yields can be dis- appointing because of the exo- to endo-cyclic isomerization of the double bond during purification on silica gel, leading in most cases to an aromatic heterocycle. [21] The success of this carbolithiation is obviously related to the cyclic character of the gem-vinyllithium products 2-Li that are protected against the Fritsch–Buttenberg–Wiechell rearrange- ment. [22] This adverse reaction was the only one observed by Satoh et al. on an acyclic analogue. [23] Overall, the efficiency of the transformation of 1 persuaded us to further investigate the chemistry of these species. The juxtaposed electrophilic and nucleophilic characters of these reagents open opportunities in heterocyclic chemistry, as illustrated below for 2a. The dual nature of 2 a-Li was first exemplified with (E)-pente- nylchlorozirconocene, itself prepared by hydrozirconation of [a] Dr. R. Lhermet, M. Ahmad, Dr. C. FressignØ, Dr. M. Durandetti, Dr. J. Maddaluno Laboratoire COBRA, CNRS UMR 6014 & FR 3038, Univ. Rouen INSA Rouen, 76821 Mt St Aignan Cedex (France) E-mail : muriel.durandetti@univ-rouen.fr jmaddalu@crihan.fr [b] Dr. B. Silvi Laboratoire de Chimie ThØorique, CNRS UMR 7616 & FR 2622, UPMC 4 Place Jussieu, 75252 Paris Cedex (France) Supporting information for this article is available on the WWW under http ://dx.doi.org/10.1002/chem.201403605. Chem. Eur. J. 2014, 20, 10249 – 10254  2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim 10249 Communication DOI: 10.1002/chem.201403605