Enantiomerically Pure Poly(oxymethylene) Helices: Correlating Helicity with Centrochirality

Abstract

A first series of enantiomerically pure helical oligo(formaldehyde)s (¼ oligo(oxymethylen)s) 16 -20 was synthesized. To induce the chiral uniformity of the helices, we used (1S)-2,2-dimethyl-1-phenylpropan-1-ol (14) to generate the end groups at the a and w terminus (Scheme 6). Propanol 14 was accessible from its racemate by acetal formation with lactol 12 and separation of the diastereoisomers (Scheme 5). The helicity of the oligomers was investigated by temperature-dependent CD, NMR, and optical-rotation studies. In addition to qualitative considerations concerning the helicity of oligo(formaldehyde)s, we performed calculations of the dimer 17 and the pentamer 20 as well as X-ray structure analyses of the dimer 17 and the tetramer 19 to establish the handedness of the helices and to correlate their sense with the absolute configuration of the inducing stereogenic center. The results may be of relevance with respect to induction and propagation of chirality in prebiotic chemistry.Introduction. -Formaldehyde is one of the most fundamental organic molecules. It is also a versatile building block in organic chemistry and found in several modifications. In the gas phase, it exists as monomeric formaldehyde, in aqueous solution, it forms a hydrate (formalin, formol), and in the solid state, it is composed of either cyclic trimers (1,3,5-trioxane, metaformaldehyde), cyclic tetramers (1,3,5,7-tetroxocane), or linear poly(oxymethylene) (paraformaldehyde), respectively [1 -3]. Short oligomers of poly(oxymethylene) were found in the tail of the Halley comet [4]. It is well accepted that paraformaldehyde forms a helix as it was shown by theoretical calculations [5], by IR spectroscopy [6], and by X-ray analysis [7 -13] (see below). During our investigation of stereoelectronic effects, we became interested in the structure of oligomers of formaldehyde, i.e., of 1, 13-diphenyl-2,4,6,8,10,12-hexaoxatridecane [14] and its corresponding heptamer (¼ 1,17-diphenyl-2,4,6,8,10,12,14,16-octaoxaheptadecane) [15], respectively. These oligomers crystallize as helices and may serve as most basic reference for the investigation of stereoelectronic effects, the anomeric effect (interaction of the n 0 lone pair of the O-atom and the s* orbital of the CÀO bond), in particular, since there are no other interacting effects [16].To synthesize for the first time an enantiomerically pure oligo(formaldehyde) (¼ oligo(oxymethylene)) helix with predicted handedness, we decided to use a chiral alcohol, (1S)-2,2-dimethyl-1-phenylpropan-1-ol (14), to generate both end groups (at the a and w terminus) of the formaldehyde oligomer. We report the synthesis and

Formaldehyde—A Key Monad of the Biomolecular System

“…Oligomers crystallize as conglomerates of crystals made up of either right-handed or left-handed molecular units [ 77 , 78 ]. It could be shown experimentally that a chirality center of the b, pl, H-type will induce helicity into an oxymethylene chain with a predictable handedness [ 79 ]. In one experiment significant asymmetric 1,10-induction of chirality was obtained in a Grignard reaction along the oxymethylene chain [ 80 ].…”

“…In one experiment significant asymmetric 1,10-induction of chirality was obtained in a Grignard reaction along the oxymethylene chain [ 80 ]. Experiments also showed that our diastereoselectivity rule also applied across an oligomeric polyoxymethylene chain [ 79 , 81 ]. In fact the helical conformation of the -O-C-O- sequence in polyformaldehyde resembles rather the atomic arrangement of -O-Si-O- helices in a quartz crystal or atomic arrangements in other inorganic crystals [ 79 ].…”

“…Experiments also showed that our diastereoselectivity rule also applied across an oligomeric polyoxymethylene chain [ 79 , 81 ]. In fact the helical conformation of the -O-C-O- sequence in polyformaldehyde resembles rather the atomic arrangement of -O-Si-O- helices in a quartz crystal or atomic arrangements in other inorganic crystals [ 79 ]. It may be hypothesized that a specific precipitation or formation of one enantiomer of a polyoxymethylene helix might easily occur in an inorganic chiral environment, thus providing the basis for further amplification of chirality based on stereoelectronic effects.…”

Chirality Transfer in the Formation of Poly(oxymethylene) Helices by Anionic Polymerization

“…By applying the b, pl, H-rule [12] [13], a right handed helix is observed when the starting and the end group has an A descriptor [14], whereas a left-handed helix is obtained with a B descriptor as start and end group, respectively. Poly(oxymethylene) serves as the most general model of the anomeric effect, namely the interaction of the n o lone pair of the O-atom and the s* orbital of the CÀO bond [15].…”

“…The (R)-1-phenylethanol was enantiomerically enriched by mixed acetal formation with the terpene carbohydrate mimic (MBE) 2 [21] to 8, followed by crystallization of 8 from MeOH for two times and then methanolysis [14]. By this protocol, we obtained the required (R)-1-phenylethanol (7) in an overall yield of 67% and an enantiomeric purity of 99.8% ee.…”