Simple Secondary Alcohols

8 MPa of hydrogen with a high substrate/catalyst molar ratio, up to 100 000, and with a high substrate concentration. The catalyst system is notable for its excellent chemoselectivity of the carbonyl group over olefinic or acetylenic bonds. Under identical conditions benzalacetone (41) is converted into the (5)-allyl alcohol 42 in 97 % ee [43c]. 

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R)-selectivity toward simple secondary alcohols carrying one small and one relatively larger substituent at the hydroxyl methane center, and the selectivity in general increases with an increase in the size diflference between two substituents. The size of the small substituent limits the reactivity of substrate toward lipase. If it exceeds a three-carbon unit, the substrate reacts very slowly or does not react at a synthetically useful rate. Accordingly, the Kazlauskas rule is useful as a guideline for predicting substrates that can be efficiently resolved by lipase as well as the stereochemistry of resolved substrates. 

Many reagents are available to oxidize a simple secondary alcohol to a ketone. Most labs would have chromium trioxide or sodium dichromate available, and the chromic acid oxidation would be simple. Bleach (sodium hypochlorite) might be a cheaper and less polluting alternative to the chromium reagents. DMP and the Swem oxidation would also work. 

Another insect pheromone synthesis illustrates one of the drawbacks of chiral pool approaches. The ambrosia beetle aggregation pheromone is called sulcatol and is a simple secondary alcohol. This pheromone poses a rather unusual synthetic problem the beetles produce it as a 65 35 mixture of enantiomers so, in order to mimic the pheromone s effect, the chemist has to synthesize both enantiomers separately and mix them together in the right proportion. 

To test whether urea could condense with a simple secondary alcohol group under acid-catalysis conditions, cyclohexanol, a simple high-boiling (bp 161 °C) alcohol, was substituted for carbohydrate in a reaction flask with urea (1 0.5 mole ratio) and acid. The mixture was heated at 65 to 122 °C for 2.5 hours. 

Urea did not react with cyclohexanol (a simple secondary alcohol) under acid catalysis to produce a product containing urea fragments. 

Simple secondary alcohols 121 (R = alkyl or aryl) are enantioselectively esterified by the reactive trichloroethyl ester 125 using porcine pancreatic lipase in anhydrous ether. The products, one enantiomer of 121 and the other enantiomer of the ester 126, are both formed in >90% ee, and are easily separated from each other and from the insoluble enzyme.29... 

Though not so general as the reactions we have just seen, the catalysed addition of dialkyl zincs to certain aldehydes sets a new standard for catalysis that needs some explaining. Dialkyl zincs add to the pyrimidine aldehyde 216 under catalysis from amino alcohols, amino acids such as leucine 219, hydroxy acids, and simple secondary alcohols or amines such as 218 to give enantiomerically enriched alcohols 217. Plain sailing so far, except for the extraordinary range of catalysts. 

The enantioselectivity of PPL depends on discrimination in binding of the substrate. In the case of acylation of simple secondary alcohols, there is poor discrimination for 2-butanol, but 2-hexanol exhibits the maximal E value, and larger alcohols show good enantioselectivity. (The definition of E is given on p. 140.)... 

Simple secondary alcohols 16 are also easily resolved with brucine to give 100% ee of 16a [[ocJd 32.3° (c 1.0 in MeOH)] and 16b [[ [[, 34.4° (c 1.0 in MeOH)] However, in the cases of 15 and 16, a sterically bulky group such as t-Bu or CCI3 is necessary for efficient optical resolution. 

Chromatography Gas chromatographic analysis of the diastereomeric carbamates from linalool was carried out on a DB-1 column at temperatures between 150 and 200 °C [30] R(-F )-phenylethylcarbamates of several simple secondary alcohols were separated on a Carbowax 20M column [32]. 

Conversion of alcohols to hydrocarbons by generation of carbenium ions, using protic acid, and then transfer of hydrogen from an organosilane to the cation, is unsatisfactory if either the carbenium ion is formed only in low concentrations or if it tends to rearrange or eliminate. These problems are somewhat alleviated by use of BF3 in dichloromethane as the acid e.g. (35) can be converted into (36) without elimination, and simple secondary alcohols are reduced. The hydride... 

A recent analysis of the role of ion pairs in the solvolysis of the arene-sulphonates of simple secondary alcohols has been made and, in further experimental studies, solvolysis of arenesulphonates of adamantanol in ethanol-water gives as products both adamantanol and the ethyl ether. The ratio of these products is different for the different arenesulphonates and further analysis suggests that products originate by nucleophilic attack by solvent upon a solvent-separated ion pair. As retention of configuration is established in this system, it is now suggested that the previous assumption of... 

According to the Kazlauskas rule, CAL-B and BCL normally provide (R)-products in the DKR of simple secondary alcohols such as 1-phenyl-l-alkanols (Scheme 5.2a). On the other hand, SC is stereocomplementary [8] to CAL-B and BCL. It provides (S)-products in the DKR of simple secondary alcohols (Scheme 5.2b). CAL-A and PSL are somehow different from CAL-B and BCL in substrate specificity and stereospecificity. They can accept sterically more demanding secondary alcohols such as 1,2-diarylethanols, which are poorly reactive with CAL-B and BCL. Interestingly, they are stereocomplementary toward these substrates CAL-A accepts... 

It was found that the Ru catalyst 11 displayed a good racemization activity under household fluorescent light [37]. Its activity was comparable to those of 5 and 6. The DKR of simple secondary alcohols with 11 and Novozym 435 gave products of excellent enantiopurity with high yields (Scheme 5.21). 

The Fu group has reported the first nonenzymatic DKR of secondary alcohols [41]. In this DKR, a planar-chiral DMAP derivative ((+)-Cg-Phg-DMAP) as the resolution catalyst was coupled with a Ru complex 6 as the racemization catalyst in the presence of an acyl carbonate (Scheme 5.25). The DKR of simple secondary alcohols provided good )delds but lower enantiopurities compared to the enzymatic DKRs. It is noteworthy that the DKR of sterically more demanding substrates carr3dng a branched side chain (isopropyl or cyclopentyl) also provided similarly good results (Chart 5.25). 

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