Acetals acyclic, conformation

The anomeric effect is also present in acyclic systems and stabilizes conformations that allow antiperiplanar (ap) alignment of the C—X bond with a lone-pair orbital of the heteroatom. Anomeric effects are prominent in determining the conformation of acetals and a-alkoxyamines, as well as a-haloethers. MO calculations (4-3IG) have found 4kcal/mol as the difference between the two conformations shown below for methoxy-methyl chloride. ... 

Simple acyclic acetals can possess six distinct conformations. 

The isotropic equivalent thermal parameters are on the whole larger than in the PbTX-1 dimethyl acetal structure or the structure of the natural product. The B values for atoms on the fused ring skeleton range from 4.7 to 12.6 A (mean square amplitudes of 0.059 and 0.16 A ). Curiously, the largest values are associated with C17-C20 of the 9-membered E ring—the ring that adopts two conformations in crystalline PbTX-1. The acyclic atoms do not have appreciably higher thermal parameters, with the exception of hydroxyl 013, which has a B of 22.4 A 2. 

Stereoelectronic factors are also important in the conformational dynamics of acyclic acetals [6] (Cosse-Barbi and Dubois, 1986). Here the usual preference for staggered conformations is supplemented by the anomeric effect (Kirby, 1983), which favours the gauche stereochemistry ( = 60°) about both central C-O bonds, mainly because this allows optimal n-rr overlap between an oxygen lone pair and the antibonding (cr ) orbital of the C-0 bond. Thus the pathway for conformational isomerization suggested by... 

Whereas preparation of a-amino acid derivatives by asymmetric allylation of an acyclic iminoglycinate gave a modest enantioselectivity (62% ee) in an early investigation [189], the use of conformationally constrained nucleophiles in an analogous alkylation resulted in high selectivities (Scheme 8E.43) [190], With 2-cyclohexenyl acetate, the alkylation of azlactones occurred with good diastereomeric ratios as well as excellent enantioselectivities. This method provides very facile access to a variety of a-alkylamino acids, which are difficult to synthesize by other methods. When a series of azlactones were alkylated with a prochiral gem-diacetate, excellent enantioselectivities were uniformly obtained for both the major and minor diastereom-ers (Eq. 8E.20 and Table 8E.12). 

Conformational analysis explains why the relatively strained 2,6-dioxa-bicyclo[3.2.1]octane skeleton 98 of 3,6-anhydro-D-gluco- and -D-manno-pyranose tends to recyclize rapidly in the presence of methanolic hydrogen chloride into the less-strained 2,6-dioxabicyclo[3.3.0]octane skeleton 99 of the 3,6-anhydrohexofuranose. Obviously, such rearrangement cannot take place with the galacto or talo configurations, and consequently, acyclic acetals are formed.390,391... 

D-(+)-galactose (15) is an example of the consecutive numbering of the carbon ring atoms in a monosaccharide (disaccharide see p. 253). Carbohydrates can exist in a cyclic and an acyclic structure. For this reason there is a special position in the structure of a monosaccharide, the carbon atom C-l and so called anomeric center. You can see that there is an equilibrium between er-anomer a-15 and / -anomer /3-15 of D-(+)-glucopyranose over the acyclic aldehyde structure 16. Both are cyclic hemi-acetals. The /Tanomer is the preferred conformation, but there are a few effects, like sterical or stereoelectronical effects (anomeric effect, inverse anomeric effect), which have influence on the a /i rate. 

Despite the development of various intermolecular radical addition methods, those studies have rarely accommodated additional functionality, our discovery of the manganese-mediated photolysis conditions notwithstanding. Prior to that discovery, we began to elaborate an alternative strategy which employs temporary tethers ([115, 116] reviews of silicon-tethered reactions [117-120]) (silyl ether or acetal linkages) linking radical and acceptor. In this scenario the C-C bond is constructed via cyclization, in which internal conformational constraints can control diaster-eoselectivity. The tether itself would be converted to useful functionality upon cleavage, and once the tether is cleaved the net result may be considered as formal acyclic stereocontrol. ... 

Among the most widespread classes of acyclic compounds to exhibit stereoelectronic control over conformation are acetals. Take the simple acetal of formaldehyde and methanol, for example what is its conformation An obvious suggestion is to draw it fully extended so that every group is fully anti-periplanar to every other—this would be the lowest-energy conformation of pentane, which you get if you just replace the Os with CH2S. 

As described in Section 6.3.4, activation of coordinated dienols (by protonation) or coordinated dienol acetates (by treatment with Lewis acid) affords the corresponding (pentadienyl)iron cations (248) (Scheme 69). Since the acyclic pentadienyl cationic complexes do not have the geometrical constraints of their cyclic counterparts, they can potentially adopt either a cisoid ( U ) or transoid ( S , sickle) conformation. Nearly all of the (pentadienyl)iron cations prepared appear to be in the cisoid conformation by H NMR spectroscopy. Only a single, sterically biased transoid pentadienyl cation (269) has been spectroscopically observed, but not isolated (equation 66). Owing to their potential to undergo U to S conformational inversion in solution, and owing to the considerably higher reactivity of the less stable S conformer, the (pentadienyl)iron cations are considerably more sensitive to moisture than their cyclic counterparts. 

A complete first-order analysis of the quinoxaline tetra-acetate confirms the acyclic structure. Coupling constants (7i 2 3-0, 72 3 8 5, /4 a, 4b 12-0, 73, 4a 3-0, Js 4b 5 5 c./sec.) for the acyclic chain, were obtained that were indicative of a high degree of conformational purity and which were in agreement with an extended planar zig-zag arrangement as the favoured conformation. 

Analogous agreement between calculation and experiment (NMR) as far as the preferred conformation of the acetal grouping is concerned was found by Anderson et al. (58) for some simple acyclic acetals. 

The importance of parallel 1,3-interactions in determining the favored conformational state of acyclic sugar derivatives in solution was also apparent from n.m.r.-spectral studies of polyhydroxyalkyl-quinoxalines in methyl sulfoxide, and of their acetates in carbon tetrachloride. 

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