Synclinal arrangement

It has been observed that the best neutral cation carriers have the synclinal arrangement of binding atoms in the backbone (see 7.2). Syntheses of both an aliphatic and aromatic ligand are shown below in Eqs. (7.12) and (7.13). 

Proton resonances for aU residues were assigned using a combination of COSY, TOCSY, HSQC, and HMBC experiments. The large values of y(NH/H-C(/9)) and the small values of J(H-C(a)/H-C(y9) were indicative of antiperiplanar and synclinal arrangements respectively, around those bonds. In addition, medium-range NOE connectivities H-C(/ )i/NH +i, H-C(a)i/NH, + i, NHi/NH +i were consistent... 

Fig. 2.47 The (P)-2.5-helical structure of N.N -linked oligoureas as determined by NMR meaurements in pyridine-c/5. (A) Stereo-view along the helix axis of a low energy conformer of nonamer 178 generated by restrained molecular dynamics calculations. (Adapted from [274]). The helix is characterized by (i) a rigid +)-SYnclinal arrangement around the C(a)-...

Both anti-synclinal and anft -periplanar TSs are considered to be feasible. These differ in the relative orientation of the C=C and C=0 bonds. The anti-synclinal arrangement is usually preferred.94... 

In the course of the total synthesis of enmein, Fujita and co-workers (7) have discovered that the intramolecular cyclization of the enolate 23 of the corresponding tetracyclic keto-aldehyde at room temperature gave only ketol 24. However, when the same reaction is conducted at 60°C, thermodynamically controlled conditions prevail, and the epimeric product 25 is obtained. Inspection of molecular models indicates that the kinetically controlled product 24 is again the result of an anti peri planar arrangement of the enolate and the aldehyde double-bonds. Also, as in the previous examples, the isomer 25 comes from a synclinal arrangement of the reacting functional groups. 

The stereochemical outcome of this new annulation process can be rationalized by assuming the transition state structure 10. The synclinal arrangement of the respective hydrogen atoms exclusively gives the all-cw-annulation product 9a. 

In contrast with the thermal reactions, jyn-homoallylic alcohols were found to be the major adducts of both ( )- and (Z)-allylic stannanes (Table 5). These findings were interpreted by assuming an acychc transition state for the addition in which steric interactions between the aldehyde substituent R and the Me substituent of the stannane were the controlling factor (Fig. 1) [14]. An antiperiplanar arrangement was initially proposed, but later work has implicated synclinal arrangements in certain cases. It has also been found that anti products may result as the major or exclusive isomers from such additions. The issue is a complex one and multiple factors, including orbital overlap, may be operative. 

It is suggested that these findings are best accommodated by a synclinal arrangement in the transition state which is favored by HOMO-LUMO orbital interactions, as previously suggested for certain intramolecular additions (Fig. 5). It should be noted that antiperiplanar or the alternative synclinal orientation for these transition states would result in unfavorable steric interactions between the aldehyde substituent, R, and the vinyl Me or (especially) R. ... 

It is suggested that steric effects tend to destabilize the antiperiplanar transition state normally associated with the formation of syn adducts in such reactions (Fig. 9). The alternative synclinal arrangement might benefit from favorable HOMO-LUMO interactions (see Fig. 3). 

In all examples examined the syn adduct was strongly favored. It should be noted that the thermal reaction affords the syn adduct which must be formed via a synclinal arrangement because of the cyclic nature of the transition state. Two arguments were advanced to explain the preference for a synclinal transition state in Lewis acid-promoted additions. The first of these entailed Coulombic attractive forces between the developing positive charge at the /3-position of the allylic stannane and the electron-... 

When an allylsilane containing a C(3) substituent reacts with an aldehyde, two new stereogenic centers are established. The reaction of ( )- and (Z)-2-butenyI-trialkylsilanes with aldehydes was first reported by Hayashi and Kumada in 1983 [28]. In these studies either ( )- and (Z)-2-butenyltrimethylsilane or ( )- and (Z)-cinnamyltrimethylsilane combined with various aldehydes in the presence of TiCl4 (Scheme 10-9). The ( )-2-butenylsilane and ( )-cinnamylsilane both afford >95 f of the syn diastereomer upon reaction with either propanal, isobutyraldehyde, or pivalaldehyde. When the Z-silanes were subjected to the same reaction conditions much lower selectivities were observed (65-72% syn selectivity). An acyclic transition structure with an antiperiplanar arrangement of double bonds was proposed to account for the diastereoselectivity observed in these reactions. A transition stmcture which includes a synclinal arrangement of double bonds may be necessary to explain the lower selectivities observed with the Z-allylsilanes. 

The relative disposition of the tin electrofuge (Se stereochemistry) has been established in the study of model system 87 [74], The cyclization of compounds m-87 and /-87 with various reagents could afford the four diastereomeric alcohols ( )- and (Z)-14-15 (Scheme 10-40). The alcohols ( )-14 and (Z)-14 result from reaction through a synclinal arrangement of double bonds in the transition structure. The alcohols ( )-15 and (Z)-15 result from reaction through an antiperiplanar arrangement of double bonds in the transition structure. The position of the deuterium can then be established in order to determine if the reaction proceeds through a syn or anti Se pathway. 

Six potential transition structure arrays for the ( )- and (Z)-2-butenylstannanes were considered to explain the observed selectivity (Fig. 10-2). For (F)-85, transition structures E2, E3, and 5 would appear to be favored based on steric arguments. The high syn selectivity observed with ( )-85 is believed to result from a preference for the sterically unencumbered syn-synclinal arrangement E2 over the other synclinal and antiperiplanar arrangements. No particular transition structure is favored upon inspection of the (Z)-85/aldehyde pairs. This is indeed observed empirically, as the addition reactions with the Z-2-butenylstannanes are much less selective than the corresponding E-stannanes. 

Keck has also described a mechanistic study of the intra-molecular allylations of Z-16 and -19 under a variety of conditions.These results are summarized in Scheme 5.2.4, as the Z-16 consistently gave the major product 18 upon treatment with Brpnsted and Lewis acids. The observed stereoselectivity is rationalized through the synclinal arrangement 17. 

The reaction of ( /Z)-2-butenyltri-n-butylstannane with aldehyde 44, as reported by Keck and coworkers 2 occurred with 1,3-asymmetric induction to yield 45 via the synclinal arrangement, illustrated from the Evans model 46 (Scheme 5.2.11). 

These characteristics of reinforcing features for 1,2- and 1,3-asymmetric induction are applied in the case of complex aldehyde 47, in combination with the steric preference for a synclinal arrangement in the C-1 substituted stannane 48, to afford high diastereoselection in the synthesis of alcohol 49, a segment of spongistatin 1 (Scheme 5.2.12).23... 

Yamamoto has reported the desymmetrizing intra-molecular cyclization of the 1,3-diketone 97 for diastereoselective formation of cis-cis 98 vs. cis-trans 99. Optimized conditions with SnCU led to the jS-chelation in the synclinal arrangement 100 to give 98, whereas the use of TiCU facilitated rapid transmetalation of the organostannane yielding 99 (Scheme 5.2.22).22... 

Yamamoto and coworkers have demonstrated intra-molecular examples of the addition of allylic stannanes to imininm ions with good to excellent yields. The incorporation of chirality using (/ )-(+)-1-phenylethylamine provides for facial selectivity in the Lewis acid-promoted ring closure of 193. Trans-tetrahydropyranyl amine 195 is obtained as the major product using a variety of Lewis acids resulting from the synclinal arrangement 194, which leads to diequatorial substitution (Scheme 5.2.43). 

The transmetalation process essentially leads to a new allylic nucleophile, which may exhibit very different properties compared to the starting stannane. A change in diastereofacial selectivity is often observed. For example, stannane 201 reacts with 3-methylbutanal to yield primarily the l,4syn product 202 via an internally coordinated synclinal arrangement 203 (Scheme 5.2.45). 

Figure 5.2 illustrates the six possible open transition structures for the Lewis acid mediated addition of allyl metals to an aldehyde. Note that for each topicity, there are two synclinal arrangements and one antiperiplanar. Several factors must be considered in explaining the observed ul topicity of these reactions (giving syn relative configuration in the products), and a number of rationales have been offered. If one assumes that the conformation is antiperiplanar in the transition state, then structure a would be favored over d, since this arrangement minimizes the interaction between in the aldehyde substituent, R, and the methyl of the crotyl group. 

On the other hand, Seebach suggested in 1981 that the topicity of a number of reactions (including these) may be explained by having the double bonds oriented in a synclinal arrangement. He reasoned that steric repulsion between the R and... 

Later, studies of intramolecular silane [37] and stannane [39] additions offered a direct comparison between synclinal arrangement c and antiperiplanar arrangement... 

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