1,3-Diethynylallenes (DEAs): enantioselective synthesis, absolute configuration, and chiral induction in 1,1,4,4-tetracyanobuta-1,3-dienes (TCBDs).

In 1875 van t Hoff predicted that in cumulenes with an even number of double bonds the four substituents must be arranged in two perpendicular planes. Van t Hoff’s proposal implied that allenes must be chiral when appropriately substituted. The predictions were confirmed when the first optically active allenes were described in 1935. For 1,3-dimethylallene, the activation enthalpy for rotational isomerism leading to racemization was determined by Roth et al. as DH = 45.07 kcal mol . In 1952, Celmer and Solomons recognized that optically active allenes also occur in nature. Since then, a number of natural chiral allenes have been found. Today, allenes are versatile starting materials and intermediates in organic synthesis because their double bonds participate in all types of addition processes, their terminal, acidic C H bonds are easily replaced by functional groups, and their axial chirality is increasingly exploited in stereoselective synthesis. We have been involved in the preparation of ethynylated allenes as building blocks for the construction of linear and macrocyclic carbon-rich scaffolds through oxidative acetylenic coupling. Following the synthesis of a first series of stable 1,3-diethynylallenes (DEAs), we proceeded with the preparation of shape-persistent macrocycles with allenoacetylenic carbon backbones. Although DEAs are axially chiral, racemic mixtures were previously used in our group for acetylenic scaffolding. Recently, we reported the synthesis of optically enriched DEA 1 a in 25 % yield and with an enantiomer ratio (e.r.) of 89:11 by Pd-mediated SN2’-type cross-coupling of alkyne 2 a with the optically pure bispropargylic ester (S)-3. The absolute configuration of the allene was tentatively assigned as (P) on the basis of an anti-SN2’-type addition of 2 a to (S)-3, as previously reported for enantioselective and diastereoselective Pd-mediated SN2’-type cross-coupling reactions. Here, we give X-ray crystallographic evidence that the enantioselective Pd-mediated addition of alkynes 2 to (S)-3 actually proceeds under opposite stereocontrol, leading to (M)-1, thereby providing the first example for a Pd-mediated enantioselective syn-SN2’-type cross-coupling reaction. We show that 4-N,N-dimethylanilino (DMA) donor-substituted optically active DEAs undergo photoisomerization leading to racemization. They also react in a facile [2+2] cycloaddition with tetracyanoethene (TCNE) to form, after retrocycloaddition, optically active, photostable 1,1,4,4-tetracyanobuta-1,3-diene (TCBD) derivatives. In these compounds, chiral induction from the optically active allene moiety in the TCBD chromophore is observed by circular dichroism (CD) spectroscopy. First, we undertook further studies to improve both the yield and the enantioselectivity of the previously reported synthesis of optically active DEAs. Alkynes 2 a, b with different protecting groups were used to enable selective deprotection, providing subsequent access to oligomers in a controlled manner (Scheme 1, Table 1). The e.r. of Me3Siprotected DEA 1 a was determined after derivatization with the Mosher acid chloride and the e.r. of 1 b by recycling HPLC on the chiral stationary phase (CSP) WHELK-O1 (hexane/0.25 % iPrOH) after removal of the iPr3Si group with nBu4NF/THF (see Supporting Information). Increasing the amount of base from 0.4 to 2.1 equiv was essential to improve the yield considerably without affecting the enantioselectivity (entries 1 and 2, Table 1). When the acetonide-protected acetylene 2 b was used, a lower reactivity was observed. Raising the temperature from 30 to 50 8C [a] Dr. J. L. Alonso-G mez, Dr. P. Schanen, P. Rivera-Fuentes, P. Seiler, Prof. Dr. F. Diederich Laboratorium f r Organische Chemie, ETH Zurich Hçnggerberg, HCI, 8093 Zurich (Switzerland) Fax: (+41) 44-632-1109 E-mail : diederich@org.chem.ethz.ch Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/chem.200801456.