A General and Versatile Method for CC Cross‐Coupling Synthesis of Conjugated Enynes: One‐Pot Sequence Starting from Carbonyl Compounds

Abstract

In light of the pivotal role of the carbonyl group in organic synthesis, [1] new general transformations of the carbonyl compounds are always of particular importance. This is why the relatively recent discovery of transition-metal-catalyzed reactions of alkenyl triflates, readily available from enolizable carbonyl precursors, immediately found widespread application.[2] Following this line of research, alkenyl 1,1,2,2,3,3,4,4,4-nonafluorobutane-1-sulfonates (hereinafter referred to alkenyl nonaflates) were introduced and advantageously employed as a useful alternative to the triflates in Heck, [3] Negishi, [4] Stille, [5] and Sonogashira [6] coupling reactions. Routinely, the coupling protocols consist of two steps that include O-sulfonylation of the starting carbonyl compounds, followed by Pd-catalyzed CÀC cross-coupling of the isolated alkenyl perfluoroalkanesulfonate leading to the desired products. Alternatively, Reissig and co-workers established that isolation and purification of the alkenyl nonaflates is not necessary for the subsequent coupling reaction provided that the nonaflates are generated from trimethylsilyl enol ethers and the mild sulfonylating reagent nonafluorobutane-1-sulfonyl fluoride (NfF) [7] under catalysis by fluoride ion. This resulted in the development of a general, one-pot transformation of trimethylsilyl enol ethers into 1,3-dienes by in situ generation of alkenyl nonaflates followed by Heck reactions.[8] However, it requires an extra step to obtain the requisite trimethylsilyl enolates from the ultimate precursors, ketones or aldehydes. This requirement serves to highlight a major challenge in the development of general and straightforward coupling methods, namely, the conversion of carbon-[*] Dr.

Pd‐Catalyzed Difluoromethylation of Vinyl Bromides, Triflates, Tosylates, and Nonaflates

“…Because the halogen anion is capable of binding easily to [(dppf)Pd(vinyl)(OTf)] to form more stable [(dppf)Pd(vinyl)Br],i ti sl ikely that the addition of KBr facilitates the transmetalation step and the catalytic cycle thereafter.V arious multi-substituted cyclic and acyclicv inyl triflates were difluoromethylated in good to excellent yields under these conditions (Scheme 3). Likewise, reactions of vinyl nonaflates [19] occurred smoothly under these conditions in good yields (Scheme 3, 5c and 5g).…”

“…Interestingly,t he yield was decreased when the reactiont ime was elongated to 48 ho rt he reaction temperature wasi ncreasedt o6 0 8 Cf or 12 h. We attribute this decrease in the yield of the desired product to the palladium-mediated irreversible oxidative addition of the allylic CÀFb ond in difluoromethylateda lkenes under the basic conditions. In fact, only 40 % yield of the b-difluoromethylated styrene was detected by 19 FNMR spectroscopy when the reaction was carriedo ut in dioxane at 60 8Cf or 4h in the presence of 10 mol %[ Pd(dba) 2 ], 20 mol %D PPF and 1.0 equivalent of NaOtBu. When other activators, such as KF,CsF or TBAF,were used, the yields of the desired product were less than 10 %.…”

Total Synthesis of Myceliothermophins C, D, and E

“…Exposure of this mixture to Li naphthalide [15] at À30 8C induced the expected radical-based rearrangement, generating, upon oxidation of the resulting mixture of allylic alcohols using DMP, [16] enone 20 in 79 % overall yield for the two steps. Upon extensive experimentation, it was found that slow addition of allyltrimethylsilane to enone 20 in CH 2 Cl 2 in the presence of TiCl 4 (Hosomi-Sakurai reaction) [17] [18] Reduction of the carbonyl group within the latter compound with DIBAL followed by dehydration (POCl 3 , py) then led to the corresponding acetylenic olefin, which was . subjected to sequential zirconium-promoted carboalumination/iodination [19] (81 % yield) and Pd-catalyzed Negishi coupling [20] with Me 2 Zn (94 % yield) to give intermediate 25 via vinyl iodide 24.…”

The LANCA three-component reaction to highly substituted β-ketoenamides – versatile intermediates for the synthesis of functionalized pyridine, pyrimidine, oxazole and quinoxaline derivatives

“…The reduction of OX7 followed by elimination to OX21 proceeded smoothly and as subsequent transformation a Heck reaction with alkenyl nonaflate 10 was performed delivering OX22 . The conversion of OX7 to alkyne OX23 applied the protocol of Lyapkalo et al [ 59 ] using Schwesinger’s base [ 60 ] as crucial reagent. First, the corresponding nonaflate is generated from OX7 that immediately underwent elimination to the alkyne.…”