Sterically hindered bonds

On Pt and Pd, cleavage of the C-O bond results from a hydrogenolytic cleavage, whereas on Ni and Cu, an insertion mechanism occurs. The regiose-lectivity of the two mechanism is different. The less sterically hindered bond (b) is cleaved on Pt and Pd, whereas the more hindered bond (a) is cleaved on Ni and Cu (Scheme 4.62). 

The insertion is also promoted by methyl substitution. In the case of 1,1-dimethyloxiranes, the sterically hindered bond is broken on a Pt catalyst too (Scheme 4.63). 

In the case of methyloxirane, however, on Pt and Pd catalysts the extent of the rupture of the sterically hindered bond is indicative of the electrophilic character of the catalyst. Unsupported or silica-supported ion-exchanged catalysts cleave the sterically less hindered bond, whereas on the impregnated catalysts, the rupture of the more hindered C-O bond is dominant.290 It is likely that Pt or Pd surface metal ions are responsible for the rupture of the sterically more hindered bond and residual chlorine from the catalyst preparation can stabilize these ions in the hydrogen atmosphere. 

Similar arguments apply to the effect of bulky substituents, which sterically hinder bond rotations and hence raise the T. This can clearly be seen in the examples given in Figure 10-64. (The Tg of polyethylene turned... 

The numerical value of Flory s characteristic ratio depends on the local stiffness of the polymer chain with typical numbers of 7-9 for many flexible polymers. The values of the characteristic ratios of some common polymers are listed in Table 2.1. There is a tendency for polymers with bulkier side groups to have higher C c, owing to the side groups sterically hindering bond rotation (as in polystyrene), but there are many exceptions to this general tendency (such as polyethylene). 

Oxiranes can be hydrogenolyzed easily alcohols and oxo compounds are formed as the result of primary processes [11,20,21]. The less sterically hindered bond is cleaved on Pt and Pd whereas the more hindered bond is broken on Ni and Cu. The rates of transformation of dimethyloxirane stereoisomers were also different on these metals, c/5-2,3-Dimethyloxirane is transformed much more rapidly than the trans isomer on Pt and Pd catalysts, whereas on Ni the two isomers are converted at almost the same rate [22]. Solid-phase hydrogenolysis of oxiranes on supported palladium catalysts has also been reported [23]. 

Interest in the synthesis of sterically hindered bonds between boron and the heavier Group 15 elements continues to parallel similar interest in the chemistry of Al, Ga and In, a fertile area in recent years. The most recent report on the reaction of R2BCI and LiPR 2 gave monomeric phoshinoboranes only when R = Cy, Bu, R = Bu. in other instances, the de-hydro-... 

The hydrogenolyaia of cyclopropane rings (C—C bond cleavage) has been described on p, 105. In syntheses of complex molecules reductive cleavage of alcohols, epoxides, and enol ethers of 5-keto esters are the most important examples, and some selectivity rules will be given. Primary alcohols are converted into tosylates much faster than secondary alcohols. The tosylate group is substituted by hydrogen upon treatment with LiAlH (W. Zorbach, 1961). Epoxides are also easily opened by LiAlH. The hydride ion attacks the less hindered carbon atom of the epoxide (H.B. Henhest, 1956). The reduction of sterically hindered enol ethers of 9-keto esters with lithium in ammonia leads to the a,/S-unsaturated ester and subsequently to the saturated ester in reasonable yields (R.M. Coates, 1970). Tributyltin hydride reduces halides to hydrocarbons stereoselectively in a free-radical chain reaction (L.W. Menapace, 1964) and reacts only slowly with C 0 and C—C double bonds (W.T. Brady, 1970 H.G. Kuivila, 1968). 

Attention should be paid to the fact that the ratio of Pd and phosphine ligand in active catalysts is crucial for determining the reaction paths. It is believed that dba is displaced completely with phosphines when Pd2(dba)3 is mixed with phosphines in solution. However the displacement is not eom-plcte[16]. Also, it should be considered that dba itself is a monodentate alkene ligand, and it may inhibit the coordination of a sterically hindered olefinic bond in substrates. In such a case, no reaction takes place, and it is recommended to prepare Pd(0) catalysts by the reaction of Pd(OAc)2 with a definite amount of phosphinesflO]. In this way a coordinatively unsaturated Pd(0) catalyst can be generated. Preparation of Pd3(tbaa)3 tbaa == tribenzylidene-acetylacetone) was reported[17], but the complex actually obtained was Pd(dba)2[l8],... 

The sp hybridized carbon of an acyl chloride is less sterically hindered than the sp hybridized carbon of an alkyl chloride making an acyl chloride more open toward nude ophilic attack Also unlike the 8 2 transition state or a carbocation intermediate m an Stvfl reaction the tetrahedral intermediate m nucleophilic acyl substitution has a stable arrangement of bonds and can be formed via a lower energy transition state... 

This reaction is reported to proceed at a rapid rate, with over 25% conversion in less than 0.001 s [3]. It can also proceed at very low temperatures, as in the middle of winter. Most primary substituted urea linkages, referred to as urea bonds, are more thermally stable than urethane bonds, by 20-30°C, but not in all cases. Polyamines based on aromatic amines are normally somewhat slower, especially if there are additional electron withdrawing moieties on the aromatic ring, such as chlorine or ester linkages [4]. Use of aliphatic isocyanates, such as methylene bis-4,4 -(cyclohexylisocyanate) (HnMDI), in place of MDI, has been shown to slow the gelation rate to about 60 s, with an amine chain extender present. Sterically hindered secondary amine-terminated polyols, in conjunction with certain aliphatic isocyanates, are reported to have slower gelation times, in some cases as long as 24 h [4]. 

Other examples of the successful displacement of tosylates are the preparation of 31 -, 16a-,16j - and27- labeled steroids. This displacement reaction fails, however, with certain C-18 and C-19 alcohol derivatives which give mainly O—S instead of C—O bond cleavage. Unsatisfactory results were also obtained with sterically hindered tosylate esters at C-11, C-12 and C-20, which give considerable amounts of olefinic products in addition to O—S bond cleavage. ... 

Isotope labeling by derivative formation with deuterated reagents is useful for the preparation of analogs such as dg-acetonides, da-acetates, da-methyl ethers, dg-methyl esters, etc. The required reagents are either commercially available or can be easily prepared. (The preparation of da-methyl iodide is described in section IX-F. Various procedures are reported in the literature for the preparation of dg-acetone, da-diazometh-ane57.i63.i73 and da-acetyl chloride. ) These reactions can be carried out under the usual conditions and they need no further discussion. A convenient procedure has been reported for the da-methylation of sterically hindered or hydrogen bonded phenolic hydroxyl functions by using da-methyl iodide and sodium hydroxide in dimethyl sulfoxide solution. This procedure should be equally applicable to the preparation of estradiol da-methyl ether derivatives. 

A more efficient agent than peroxy compounds for the epoxidation of fluoro-olefins with nonfluonnated double bond is the hypofluorous acid-acetomtrile complex [22] Perfluoroalkylethenes react with this agent at room temperature within 2-3 h with moderate yields (equation 13), whereas olefins with strongly electron-deficient double bond or electron-poor, sterically hindered olefins, for example l,2-bis(perfluorobutyl)ethene and perfluoro-(l-alkylethyl)ethenes, are practically inert [22] Epoxidation of a mixture of 3 perfluoroalkyl-1-propenes at 0 C IS finished after 10 mm in 80% yield [22] The trifluorovinyl group in partially fluorinated dienes is not affected by this agent [22] (equation 13)... 

Because the new carbon-carbon bond is formed by an SN2-type reaction the alkyl halide must not be sterically hindered. Methyl and primary alkyl halides work best secondary alkyl halides give lower yields. Tertiary alkyl halides fail, reacting only by elimination, not substitution. 

FIGURE 11.12 Rotation around the glycosidic bond is sterically hindered syn versus anti conformations in nucleosides are shown. 

The first SN2 reaction variable to look at is the structure of the substrate. Because the S, j2 transition state involves partial bond formation between the incoming nucleophile and the alkyl halide carbon atom, it seems reasonable that a hindered, bulky substrate should prevent easy approach of the nucleophile, making bond formation difficult. In other words, the transition state for reaction of a sterically hindered alkvl halide, whose carbon atom is "shielded" from approach of the incoming nucleophile, is higher in energy... 

High-valent ruthenium oxides (e. g., Ru04) are powerful oxidants and react readily with olefins, mostly resulting in cleavage of the double bond [132]. If reactions are performed with very short reaction times (0.5 min.) at 0 °C it is possible to control the reactivity better and thereby to obtain ds-diols. On the other hand, the use of less reactive, low-valent ruthenium complexes in combination with various terminal oxidants for the preparation of epoxides from simple olefins has been described [133]. In the more successful earlier cases, ruthenium porphyrins were used as catalysts, especially in combination with N-oxides as terminal oxidants [134, 135, 136]. Two examples are shown in Scheme 6.20, terminal olefins being oxidized in the presence of catalytic amounts of Ru-porphyrins 25 and 26 with the sterically hindered 2,6-dichloropyridine N-oxide (2,6-DCPNO) as oxidant. The use... 

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