1- Heptanol reaction with hydrogen

Labeling studies provided some evidence that aldehydes are not intermediates in the formation of heptanol from 1-octene but a hydroxy carbene-like intermediate (Scheme 5.50) [63]. The latter derives from the protonation of the relevant Rh-acyl complex by ethanol and benefits from the high electron density at the metal center, which is caused by trialkylphosphines. The reaction with hydrogen (here D2) produces the alcohol. A similar mechanism was suggested for the tandem reaction with 2-propen-l-ol as a substrate [64]. 

Sketch a potential energy diagram for the reaction of 1 heptanol with hydrogen bromide paying careful attention to the positioning and structures of the intermediates and transition states... 

The reaction was carried out with CALB and diruthenium complex 1 in the presence of 2,6-dimethyl-4-heptanol or molecular hydrogen (latm). In the case of 1-phenylvinyl acetate, (R)-l-phenylethyl acetate was obtained in 89% yield and 98% ee (Scheme 1.14) [15a]. 

Unlike tertiary and secondary carbocations, methyl and primary carbocations are too high in energy to be intermediates in chemical reactions. However, methyl and primary alcohols are converted, albeit rather slowly, to alkyl halides on treatment with hydrogen halides. Therefore, they must follow a different meehanism, one that avoids carbocation intermediates. This alternative process is outlined in Mechanism 4.2 for the reaction of 1-heptanol with hydrogen bromide. 

As displayed in Figure 10.4, the ricinoleic acid (here the transesterification product, methyl ricinoleate) is subjected to a pyrolysis step. More specifically, the cracking pyrolysis takes place at 500-600 °C in presence of water vapour but in the absence of air to release undecenoic acid (methyl undecenoate) and heptaldehyde. The side product heptaldehyde is a source of several seven carbon-containing co-products such as heptanoic acid or heptanol. The main intermediate, methyl undecenoate, is further treated [9]. Firstly, it is hydrolysed to yield undecenoic acid. Then, it is reacted with hydrogen bromide in a nonpolar solvent to enable the reverse addition reaction, which forms bromoundecanoic acid. Finally, upon ammonia treatment, the crystalline solid 11-aminoundecanoic acid is formed and separated. 

Although Pd, Ni, Ru, and Pd catalyze hydrogenation of ketones and aldehydes, a platinum catalyst is usually the best choice because the yields are better and there are fewer side reactions. Platinum oxide (Pt02)—sometimes called Adam s catalyst after Roger Adams (United States 1889-1971)—is commonly used. The choice of catalyst depends on the reaction conditions, the nature of the carbonyl compound, etc. The reaction of heptanal with hydrogen gas in the presence of a ruthenium catalyst (Ru/C), in 80% aqueous ethanol, gave 1-heptanol in near quantitative yield. ... 

The catalytic alcohol racemization with diruthenium catalyst 1 is based on the reversible transfer hydrogenation mechanism. Meanwhile, the problem of ketone formation in the DKR of secondary alcohols with 1 was identified due to the liberation of molecular hydrogen. Then, we envisioned a novel asymmetric reductive acetylation of ketones to circumvent the problem of ketone formation (Scheme 6). A key factor of this process was the selection of hydrogen donors compatible with the DKR conditions. 2,6-Dimethyl-4-heptanol, which cannot be acylated by lipases, was chosen as a proper hydrogen donor. Asymmetric reductive acetylation of ketones was also possible under 1 atm hydrogen in ethyl acetate, which acted as acyl donor and solvent. Ethanol formation from ethyl acetate did not cause critical problem, and various ketones were successfully transformed into the corresponding chiral acetates (Table 17). However, reaction time (96 h) was unsatisfactory. 

After succeeding in the asymmetric reductive acylation of ketones, we ventured to see if enol acetates can be used as acyl donors and precursors of ketones at the same time through deacylation and keto-enol tautomerization (Scheme 8). The overall reaction thus corresponds to the asymmetric reduction of enol acetate. For example, 1-phenylvinyl acetate was transformed to (f )-l-phenylethyl acetate by CALB and diruthenium complex 1 in the presence of 2,6-dimethyl-4-heptanol with 89% yield and 98% ee. Molecular hydrogen (1 atm) was almost equally effective for the transformation. A broad range of enol acetates were prepared from ketones and were successfully transformed into their corresponding (7 )-acetates under 1 atm H2 (Table 19). From unsymmetrical aliphatic ketones, enol acetates were obtained as the mixtures of regio- and geometrical isomers. Notably, however, the efficiency of the process was little affected by the isomeric composition of the enol acetates. 

Homs and co-workers described the linkage of ethene and C02 on a supported platinum/tin complex yielding 3-hydroxypropionic acid [73], Another approach to utilizing C02 was pursued by Tominaga and Sasaki, namely hydroformylation with C02 [74]. 1-Hexene, for instance, reads with a mixture of C02 and H2 in the presence of ruthenium dusters giving heptanals, heptanols, and, in small amounts, the undesired hexane as a result of simple hydrogenation. Mechanistically it is assumed that a retro water gas shift reaction occurs, in which CO and H20 are formed from C02 and H2. This carbon monoxide undergoes ordinary hydroformylation with the alkene and H2. 

Lithium aluminum hydride (8) reacts with ketones and aldehydes in the same way as sodium borohydride, except that LiAlH is a more powerful reducing agent. In one experiment, reaction of heptanal (13) with LiAlH4 in diethyl ether, followed by aqueous acid workup, gave 1-heptanol (16) in 86% yield. The mechanism is identical to that of borohydride in that heptanal reacts with the negatively polarized hydrogen of the Al-H unit in 8 via the four-centered transition state 14, This leads to an alkoxyalmninate product, 15, and subsequent treatment with dilute acid... 

In a typical example of this process, benzyl alcohol (3.0 mmol) was reacted with heptanol (1.0 mmol) in the presence of RuH2(CO)(PPh3)3 (4 mol%) combined with xantphos (4 mol%), silica-immobilized amine (0.9 mmol), and crotononitrile (5.0 mmol) as a hydrogen acceptor at 120 °C under microwave irradiation for 3 h to give the corresponding cross-coupled a,P-unsaturated aldehydes in 75 % yield (Scheme 39). In this reaction, the silica-immobilized amine was recycled (by simple filtration) at least five times without considerable loss in its catalytic activity. 

An example with huge economic relevance is the manufacture of 2-propyl-heptanol (2-PH) as a component of plasticizer alcohols and, on a smaller scale, for use in cosmetics [9]. On an industrial scale, the transformation is commonly conducted as a three-step approach starting with the hydroformylation of isomeric butenes, subsequent aldol reaction of formed -valeraldehyde, and, finally, combined hydrogenation of the C-C double bond and aldehyde group [10]. In a similar process, the production of the plasticizer alcohol 2-ethyl-hexanol (2-EH) is carried out [11, 12]. 

The reaction of (a-chloroalkyl)boronic esters with silicon tetrachloride does not epimerize (a-chloroalkyl)boron groups. As a test, (S)-DICHED (1-chloropentyl)-boronate (142) with potassium bifluoride was converted into potassium (1-chloro-pentyl)trifluoroborate (143), which was treated with silicon tetrachloride in THF to form (l-chloropentyl)dichloroborane (144). The dichloroborane was converted into the stable pinacol ester 145, which was transesterified to the (R)- and (5)-pinanediol esters 146 and 147, respectively (Scheme 8.33). H NMR spectra of these two di-astereomers differ sufficiently to show that each was pure and free from more than 1-2% of the other. Compound 144 was shown to react readily with diethylzinc followed by base and finally hydrogen peroxide to yield the expected (S)-3-heptanol, but this chemistry awaits further development to achieve efficient synthetic procedures. 

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