J. prakt. Chem. 338 (1996) 92-94 Journal zyx fur praktische Chemie Chemiker-Zeitung zy 0 Johann Ambrosius Barth 1996 Das Reagenz The Reagent Methoxyallene: A Reagent of Versatile Applications in Organic Synthesis Reinhold Zimmer and Faiz A. Khan Dresden, Institut fiir Organische Chemie der Technischen Universitat Received September 28th, 1995 Since the first preparation of methoxyallene (2) by Hoff, Brandsma and Arens in 1968 [l], this compound with cumulated C=C bonds has emerged as a useful and convenient C3-building block for many transformations commonly performed in organic synthesis [2]. Methoxyallene (2) is easily accessible by a two-step reaction sequence starting from propargyl alcohol (1) [I, 31. The compound is a colourless liquid (bp. 5 1-52 "C/760 Torr), and its chemical behaviour is similar to a ,,normal" enol ether (e.g. the sensitivity towards acidic hydrolysis). In the meantime, methoxyallene (2) is a commerciallyavailable reagent. zyxwvuts a) (Me0)$O2 i NaOH OH zyxwvutsrqp b) KOtBu OMe zyxwvutsr + zy c zyxwvutsrqpo -4 81% 1 2 One of the key features of methoxyallene (2) is the smooth deprotonation of the hydrogen atom at C-1 leading to the 1-lithio-1-methoxyallene (3) [3, 41. The broad utility of the lithiated intermediate 3 for synthesis is apparent from the wide ranging applications that are known in the literature [2]. The species 3 is reactive enough towards a variety of electrophiles, like alkyl halides, chlorotrimethylsilane or carbonyl compounds etc. [l, 5, 61. A subsequent hydrolysis of methoxyallene derivatives can be easily performed under acidic conditions to produce an a$-unsaturated carbonyl compound (5+6) [5]. On the other hand, C-l-hydro- xyalkylated methoxyallene derivatives like 7 are cleanly cyclised to the corresponding 2,5-dihydro-3-methoxyfuran [7]. This methodology has been successfully applied to the OMe nBuLi I THF zyxwvutsrqp or EbO c -4 Li 2 3 stereoselective synthesis of 3(2H)dihydrofurans,e.g. 3 +lO +11 [8]. Starting from methoxyallene (2) the methoxyalkyne derivative 13 can be prepared by lithiation under standard conditions, transmetallation with TiCl(OiPr)3 followed by addition of the in situ generated titanium species 12 to the a-aminoaldehyde 9 [9]. The observed regioselectivity is good (13:10 = 91 : 9), and the resulting antdsyn-selectivity of 13 is high (94% anti). The subsequentcyclisationof 13 under acidic reaction conditions yielded the y-lactone 14 [9]. Furthermore, methoxyallene (2) can also serve as the dienophile component in inverse electron demand het- ero-Diels-Alder reactions with different heterodienes 15 to give regioselectively the correspondingheterocycles 16 [lo]. For example, using the in situ generated nitrosoalkene 17, the [4+2]-cycloaddition leads to the trifluoromethyl substituted 1,2-oxazine 18 in excellent yield [~OC]. On the other hand, BuBr Bu I 4 0 Me3SiC1 CF3COOH -78 OC 6 50% siMe3 76% .- 5 Is KOtBu i DMSO -Hot 5O"Cl 1 h, & 82% 95% I 8