Palladium-catalyzed cycloaddition of alkynyl aryl ethers to allenes proceeds through o-CH activation to give 2,3-dihydro-4H-1-benzopyran derivatives containing 2,3-exo-double bonds. These benzopyran derivatives further cycloadd stereoselectively to dienophiles to give condensed polycycles.The DielsAlder reaction of 1,2-bismethylidene carbocycles with dienophiles is a straightforward method to obtain polycyclic homologues, the synthetic method being the long-standing target of synthetic chemistry.1 Thus, such a conjugated diene unit is a useful structural motif for polycyclic annulation. Representative preparative methods for 1,2-exomethylidene carbocycles are dehydrohalogenation of cyclic substrates having two adjacent halo-or pseudohalomethyl groups, 2 the Ramberg Bäcklund reaction of in situ generated allylchloromethyl sulfones, 3 and metal-mediated and -catalyzed cyclizations of enynes as well as allenyl alkynes, diynes, and bisallenes. 4,5 Among these, metal-catalyzed cyclization appears to be ideal for the synthesis of multisubstituted 1,2-bismethylidene carbocycles with high atom-economy. This approach, however, is generally limited to unimolecular reactions, and its application to intermolecular cycloadditions remains a challenge. 6 In keeping with the goal of developing such reactions, regioselective insertion of allenes into CH bonds of substrates having CC triple bonds is a promising method. 7 In this respect, we recently found that an alkynoxy group (OC¸CR) 8 works as a directing group for CH activation and a cyclization partner as well. 9,10Herein, we report the palladium-catalyzed activation of an o-C H bond of alkynoxyarenes 1 followed by cycloaddition with allenes 2 to produce a wide range of 2,3-bismethylidene-2,3-dihydro-4H-1-benzopyrans 3. The cycloadducts are extremely useful for the DielsAlder reactions with dienophiles to give condensed cycles.The reaction of 4-methoxyphenyl triisopropylsilylethynyl ether (1a) with 1,2-nonadiene (2a) gave 2,3-bismethylidenechromane derivative 3aa in 81% yield as a single regioisomer in the presence of Pd(OAc) 2 , PCy 3 , and Zn (for in situ Pd(II) reduction) in toluene at 100°C for 2 h (Table 1, Run 1). The structure of 3aa was unambiguously determined by NMR spectroscopy. It should be noted that the internal double bond of 2a readily underwent cycloaddition. The reaction of 1b (R 2 = TBDPS), 1c (R 2 = TES), and 1d (R 2 = TBDMS) proceeded to afford 3ba, 3ca, and 3da in moderate to excellent yields (Runs 24). In addition, the Me 2 PhSi-substituted alkynyl ether 1e, which was reluctant to cycloadd to alkynes, provided the desired product 3ea in 40% yield (Run 5). The presence of a silyl substituent, however, is not essential for this reaction to occur: a bulky carbonaceous group also allows the substrate to undergo the transformation, as is evidenced by substrate 1f, which despite the presence of the bulky substituent C(OMe)(CH 2 ) 5 produces 3fa in 64% yield (Run 6). The reaction of 4-MeOC 6 H 4 OC¸CMe, however, resulted in a complex mixture of products. The...

Palladium(0)-catalyzed insertion/annulation sequence between aryl silylethynyl ethers and internal alkynes was found to proceed through activation of ortho-C–H bonds assisted by alkynoxy groups and gave stereoselectively (Z)-2-silylmethylenechromenes. These products could be easily converted into 2,2-alkylated 2H-chromene derivatives, an important structural motif in medicinal chemistry and materials science. Various aryl silylethynyl ethers and alkynes can be transformed under the reaction conditions, and a wide range of chromenes is thus accessible. When unsymmetric alkynes are employed, a regioselective annulation takes place, especially those containing aryl and/or bulky substituents. Catalytic systems based on palladium(0), such as Pd(OAc)2/PCy3/Zn, [Pd(dba)2]/PCy3, or Pd(PCy3)2 exhibit excellent catalytic activity, and the best performance is observed for Pd(PCy3)2 in combination with Zn(OAc)2 as an additive. Substituents on the aryl group in the alkynyl aryl ethers rarely affect the reaction rate. Deuterium-labeling experiments suggest that the ortho-hydrogen atom migrates to the 2-methylene position in the chromene products. The cleavage of the C–H bond is considered to be the rate-determining step in these reactions.

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Palladium-catalyzed cycloaddition of alkynyl aryl ethers with isocyanates proceeds through o-CH activation to afford 2-methylidene-2H-1,4-benzoxazin-3(4H)-one derivatives. Deuterium-labeling experiment shows that o-hydrogen is cleaved selectively and migrated to 2-methylidene moiety in the product. Various substrates are applied to this transformation to afford various substituted cycloadducts. 1,4-Bis(alkynoxy)benzenes can be used for the synthesis of multicondensed cycles to afford benzo [1,2-b:4,5-b¤]bis [1,4]oxazine-3,8-dione derivatives.Straightforward CH bond functionalization by transitionmetal complexes emerged very recently as a great promise in the synthesis of high level of functionalized chemicals and for contributing to environmentally benign transformations. 1 We have been aiming to fabricate novel transformations of phenol derivatives into various heterocyclic compounds, which are an important structural motif in medicinal and material chemistry. We have recently disclosed the palladium-catalyzed CH bond activation in alkynyl ethers, 3 easily available from the corresponding phenol derivatives. 4 This CH activation strategy has a high potential for the efficient synthesis of various functionalized heterocycles. On the basis of this finding, we report herein the synthesis of 2-silylmethylidene-2H-1,4-benzoxazin-3(4H)-ones 57 from the cycloaddition of aryl silylethynyl ethers with isocyanates via o-CH cleavage.First, we ran the reaction of 4-methoxyphenyl triisopropylsilyl (TIPS)-ethynyl ether (1a) with phenylisocyanate (2a) under the typical conditions (Pd(OAc) 2 /PCy 3 /Zn and [Pd(dba) 2 ]/ PCy 3 ) for the cycloaddition of alkynyl aryl ethers with alkynes 3a and allenes, 3c but failed to afford the heterocyclic products. After screening the various parameters of reaction conditions and catalytic conditions, Pd(OAc) 2 , PCy 3 , and Lewis acidic Zn(OAc) 2 in toluene were used at 120°C for 5 h to afford 2-(Z)-triisopropylsilylmethylidene-6-methoxy-4-phenyl-2H-1,4-benzoxazin-3(4H)-one (3aa) as a colorless solid in 65% yield without the generation of other regioisomers (eq 1).8 Product 3aa was easily purified by preparative TLC. Further recrystallizations from CH 2 Cl 2 /hexane afforded analytical-level purity. The structure of 3aa was unambiguously determined by X-ray crystallographic analysis (Figure 1). 9 The observed regioselectivity is unique: addition of CH bonds to isocyanate exclusively favored the insertion of C=N bond in isocyanates into CH bonds. 10 The reaction in the absence of Zn(OAc) 2 also afforded 3aa, albeit in lower yield, probably indicating that the ligation of isocyanates to Zn(OAc) 2 enhances the reactivity toward palladium complexes. No reaction took place with substrates such as 1,4-dimethoxybenzene, triisopropylsilylethynyl phenyl ketone, aryl tributylstannylethynyl ether, and benzyltriisopropylacetylene instead of 1a, showing that the silylethynyloxy group is essential for the present reaction. 11,12 The presence of the TIPS group is essential for this reaction: less bulky si...

Palladium-Catalyzed Cycloaddition of Alkynyl Aryl Ethers to Allenes to Form a 2,3-Bismethylidene-2,3-dihydro-4H-1-benzopyran Framework. -The palladium-catalyzed cycloaddition of alkynyl aryl ethers (I) to various allenes gives benzopyran derivatives. The diene moieties of the cycloadducts are used as diene reaction partners in further Diels-Alder reactions to form linearly condensed tetracycles [cf. (VII)]. -(MINAMI, Y.; KANDA, M.; HIYAMA*, T.; Chem. Lett. 43 (2014) 2, 181-183, http://dx.doi.org/10.1246/cl.130894 ; Res. Dev. Initiative, Chuo Univ., Bunkyo, Tokyo 112, Japan; Eng.) -M. Bohle 41-156