DOI: 10.1002/chem.201101489 Calcium-Mediated Dearomatization, C À H Bond Activation, and Allylation of Alkylated and Benzannulated Pyridine Derivatives Phillip Jochmann, Valeri Leich, ThomasP. Spaniol, and Jun Okuda* [a] Introduction A vast range of bioactive molecules contain pyridine (Py) and quinoline units as essential building blocks for biologi- cal function. Thus, the development of new strategies for the preparation of this class of compounds has become an important endeavor in synthetic chemistry. [1] Apart from re- actions for the construction of substituted N-heterocycles, [2, 3] C À H bond activation and substituent modification reactions of inexpensive and readily available pyridine and quinoline derivatives play a major role in their functionalization. In the latter case, attaching activating substituents is crucial for further transformations. The introduction of olefinic func- tionalities such as vinyl or allyl substituents results in valua- ble starting materials for ring-closing metathesis, [4] epoxida- tion/dihydroxylation, [5] cyclopropanation, [5b] and polymeri- zation [6] reactions. Cross-coupling reactions, including Hiyama, [7] Kumada, [8] Negishi, [9] Stille, [10] and Suzuki– Miyaura [11] reactions, have broadened the scope of applica- tions of substituent modification reactions. Numerous reports have demonstrated that simple trans- formations of pyridine often rely on its p-deficient charac- ter. Additional activating and/or directing groups open access to a variety of pyridine derivatives when metal cataly- sis is employed. [1a, 12] Metalation is an important tool for the introduction of (hetero)organic substituents on the pyridine ring, as well as for the introduction of a pyridyl nucleophile itself. In this context, lithiated or magnesiated pyridyls are the commonly used starting materials. Alkyl lithium re- agents usually show a preference for addition over deproto- nation and often undergo unwanted coupling reactions. ortho-Lithiated or magnesiated pyridyls can easily be ob- tained by halogen–metal exchange. [13] Direct ortho-metala- tion is observed in the reactions of pyridine with many or- ganometallic compounds of early transition and f-block metals. [14] Common methods for the introduction of late transition and p-block metals often utilize the abovemen- tioned lithiated or magnesiated derivatives in metal-ex- change reactions. [13, 15, 16] Notably, there have been various re- ports on the allylation of (iso)quinolines with allylic re- agents of boron, [17] tin, [17d, 18] silicon, [12d, 17d, 18a, 19] indium, [18e, 20] and magnesium. [21] As was found for the activation of pyri- dine itself, these transformations mostly require N-acylation prior to functionalization, and, with some exceptions, give the desired allylated derivatives in yields lower than 80 %. Pyridine insertion of an in situ generated magnesium hy- dride complex has also been observed. [22] The importance of Abstract: A facile and general synthet- ic pathway for the production of dear- omatized, allylated, and C ÀH bond ac- tivated pyridine derivatives is present- ed. Reaction of the corresponding de- rivative with the previously reported reagent bisACHTUNGTRENNUNG(allyl)calcium, [CaACHTUNGTRENNUNG(C 3 H 5 ) 2 ] (1), cleanly affords the product in high yield. The range of N-heterocyclic com- pounds studied comprised 2-picoline (2), 4-picoline (3), 2,6-lutidine (4), 4- tert-butylpyridine (5), 2,2’-bipyridine (6), acridine (7), quinoline (8), and iso- quinoline (9). Depending on the substi- tution pattern of the pyridine deriva- tive, either carbometalation or C À H bond activation products are obtained. In the absence of methyl groups ortho or para to the nitrogen atom, carbome- talation leads to dearomatized prod- ucts. CACHTUNGTRENNUNG(sp 3 ) ÀH bond activation occurs at ortho and para situated methyl groups. Steric shielding of the 4-posi- tion in pyridine yields the ring-metalat- ed product through CACHTUNGTRENNUNG(sp 2 ) À H bond ac- tivation instead. The isolated com- pounds [Ca(2-CH 2 -C 5 H 4 N) 2 ACHTUNGTRENNUNG(THF)] (2b·ACHTUNGTRENNUNG(THF)), [Ca(4-CH 2 -C 5 H 4 N) 2 - ACHTUNGTRENNUNG(THF) 2 ] (3b·ACHTUNGTRENNUNG(THF) 2 ), [Ca(2-CH 2 - C 5 H 3 N-6-CH 3 ) 2 ACHTUNGTRENNUNG(THF) n ] (4b·ACHTUNGTRENNUNG(THF) n ; n = 0, 0.75), [Ca{2-C 5 H 3 N-4-CACHTUNGTRENNUNG(CH 3 ) 3 } 2 - ACHTUNGTRENNUNG(THF) 2 ](5c·ACHTUNGTRENNUNG(THF) 2 ), [CaACHTUNGTRENNUNG{4,4’-ACHTUNGTRENNUNG(C 3 H 5 ) 2 - (C 10 H 8 N 2 )}ACHTUNGTRENNUNG(THF)] (6a·ACHTUNGTRENNUNG(THF)), [Ca(NC 13 H 9 -9-C 3 H 5 ) 2 ACHTUNGTRENNUNG(THF)] (7a·- ACHTUNGTRENNUNG(THF)), [Ca(4-C 3 H 5 -C 9 H 7 N) 2 ACHTUNGTRENNUNG(THF)] (8b·ACHTUNGTRENNUNG(THF)), and [Ca(1-C 3 H 5 -C 9 H 7 N) 2 - ACHTUNGTRENNUNG(THF) 3 ](9a·ACHTUNGTRENNUNG(THF) 3 ) have been char- acterized by NMR spectroscopy and metal analysis. 9a·ACHTUNGTRENNUNG(THF) 4 and 4b·- ACHTUNGTRENNUNG(THF) 3 were additionally characterized in the solid state by X-ray diffraction experiments. 4b·ACHTUNGTRENNUNG(THF) 3 shows an aza- allyl coordination mode in the solid state. Based on the results, mechanistic aspects are discussed in the context of previous findings. Keywords: allyl ligands · allylation · calcium · nitrogen heterocycles · reaction mechanisms [a] P. Jochmann, V. Leich, Dr. T.P. Spaniol, Prof.Dr. J. Okuda Institute of Inorganic Chemistry, RWTH Aachen University Landoltweg 1, 52056 Aachen (Germany) Fax: (+ 49) 241-80-92-644 E-mail : jun.okuda@ac.rwth-aachen.de Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/chem.201101489. Chem. Eur. J. 2011, 17, 12115 – 12122  2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim 12115 FULL PAPER