Acetylenic Allenophanes: An Asymmetric Synthesis of a Bis(alleno)‐bis(butadiynyl)‐meta‐cyclophane

Abstract

We have an ongoing interest in the design and synthesis of novel cyclophanes, many of which contain a twisted conformation that imparts helical chirality [1] to the assembled molecule.[2] This helical chirality is a consequence of the number, type, and combination of unsaturated linkages present in these molecules. The synthesis and design of cyclophanes [3] and cage compounds with high carbon content in novel shapes and supramolecular geometries [4] continues to be a topic of current interest.Allenes are a unique family of organic molecules because of their diverse chemistry, axial chirality, and synthetic versatility, [5] and so investigations into allene-containing natural products and their total syntheses continue to increase.[6] Furthermore, medical applications for these compounds include employing them as inactivators of monoamine oxidase. [7] In contrast, cyclophanes that have only allene bridges (termed allenophanes) [8] have received little attention and the only reported example was prepared as a mixture of diastereomers.[8] A related family of cyclophanes comprises structures that contain both allene and acetylene bridges. These acetylenic allenophanes should also possess interesting properties. Herein, we report the first asymmetric synthesis of an acetylenic allenophane that contains two allene bridges. This compound appears to be the first cyclophane of this general class.The general structure of an acetylenic allenophane is depicted in Scheme 1. The R 1 substituents aid solubility: the absence of similar groups in the previously prepared allenophane [8] limited its solubility and prevented a full investigation into its properties. The R 2 substituents may be hydrogen atoms or alkyl groups, depending on the method selected to synthesize the allene moiety. The number of acetylene bridges may also be varied.We devised a strategy to an acetylenic allenophane related to 16 based on the dimerization of desilylated 15 (see Scheme 4). We [9a] and others [9b] observed previously that the separation of the alkyne termini dictates whether the intra-or intermolecular product dominates. Molecular modeling studies have strongly suggested that the intermolecular product is favored when the termini separation is greater than 7 .[9c] In the case of 15, the calculated alkyne separation of 8.87 [10] indicated that the intramolecular product 16 should be preferred.We initially examined the allene preparation used by Myers and Zheng for the synthesis of an allenophane in which R 2 groups are hydrogen atoms (Scheme 1). [11] This asymmetric method had the advantage that the allene precursor, a secondary propargyl alcohol, was readily available through the addition of an acetylide to an aldehyde.[12] Initially, orthoamino substituents at the aryl ring were chosen to aid solubility, but this idea had to be abandoned because electron donation from the lone pair of electrons on the nitrogen atom in the ortho-amino substituent leads to the formation of cumulene-type intermediates during allene formation (Scheme 2), and so...

Allenamides: A Powerful and Versatile Building Block in Organic Synthesis

“…Majumdar 49a reported preparation of N -enyne acrydone 97 under PTC conditions and cumulene-type allenamides 96 were proposed as intermediates (Scheme 33). …”

“…More recently, Fallis 49b suggested that allenamide 100 [another secondary allenamide] was formed from aniline substituted propargyl phosphonium ether 98 via an initial intramolecular elimination of triphenylphosphine oxide followed by trapping the cumulene intermediate 99 (Scheme 34). …”

Exploiting [2+2] cycloaddition chemistry: achievements with allenes

“…102 affording bicycle [3.2.0] products 296-298 in moderate to good yields (54-66%) without formation of other regioisomers (Scheme 99). 103 Interestingly, reaction of compound (S)-295 containing the chiral L-valine ester moiety, afforded bicycle 298 in greater than 99% ee, which indicates that the reaction proceeded without racemization of the a-amino acid ester.…”

Highly Regioselective Radical Amination of Allenes: Direct Synthesis of Allenamides and Tetrasubstituted Alkenes

“…[5] In addition, the transition-metal-catalyzed intramolecular amino-cyclizations [6] and Tr ost-Hsung N-allenylation [7] methods have also been developed in recent years. Nevertheless,most of the current methods suffer from at least one of the following drawbacks:h arsh reaction conditions (such as use of strong bases,h igh temperature), the requirement of prefunctionalization of substrates,o re mployment noble metals.H ence,ag eneral, mild, and efficient approach to the synthesis of allenamides is highly desired.…”