Of carbinols

The disadvantages associated with the Clemmensen reduction of carbonyl compounds (see 3 above), viz., (a) the production of small amounts of carbinols and unsaturated compounds as by-products, (h) the poor results obtained with many compounds of high molecular weight, (c) the non-appUcability to furan and pyrrole compounds (owing to their sensitivity to acids), and (d) the sensitivity to steric hindrance, are absent in the modified Wolff-Kishner reduction. 

Note 1. Compare Chapter VIIl-6, Exp. 1 for the effect of lithium bromide on the formation of carbinols, derived from propyne. 

In Robinson s now well-known suggestions, regarding the processes by which alkaloids may be produced in plants, two main reactions are used j the aldol condensation and the similar condensation of carbinol-amines, resulting from the combination of an aldehyde or ketone with ammonia or an amine, and containing the group. C(OH). N., with substances in which the group, CH. CO. is present. By these reactions it is possible to form the alkaloid skeleton, and the further necessary changes postulated include oxidations or reductions and elimination of water for the formation of an aromatic nucleus or of an ethylene derivative. 

Oxidation of carbinols with chromium VI— acetic acid, 228... 

During the transfer from the gas phase to the solvent CH2C12, the formation, of NO is so strongly preferred that the following two events can take place the chain termination due to formation of carbinol end groups and nitrations as successive reactions, both of which could be experimentally detected to be disturbances of the cationic propagation 122). 

A study aimed at optimizing yields in this reaction found that carbinol formation was a major competing process if the reaction was not carried out in such a way that all of the lithium compound was consumed prior to hydrolysis.113 Any excess lithium reagent that is present reacts extremely rapidly with the ketone as it is formed by hydrolysis. Another way to avoid the problem of carbinol formation is to quench the reaction mixture with trimethylsilyl chloride.114 This procedure generates the disilyl acetal, which is stable until hydrolysis. 

Kumada (44) showed that chiral ferrocenyl phosphine ligands on rhodium gave good optical yields of carbinols from prochiral ketones. 

This conclusion is in accord with the results of MINDO/3 quantum-chemical calculations. Cation 7 is also prone to undergo a rather slow degenerate rearrangement by 1,2-bridge shift (AG is about 60 kJ/mol) (Scheme 8). This rearrangement was probed via 2H NMR spectroscopy, when the 9-CD3-analog of carbinol 5 was used as precursor for carbocation generation. At -50 °C cations 6-8 transform firstly into l,l,2,3,3a,4,8b-heptamethyl-l,3a,8b-trihydrobenzopentalenium ion (9) and then (partially) into 1,1,2,3,4,4,8b-heptamethyl-l,4,8b-trihydrobenzopentalenium ion (10) (Scheme 9). 

This spectral nonequivalence for the diastereomeric solvates was originally rationalized in terms of conformers 28 (shown for TFPE as solute) where (/2)-NEA as its preferred rotamer (dictated by the peri interaction) interacts primarily with the carbinol hydroxyl and populates the conformers shown through an aryl-aryl attraction. Thus, in (5, )-28, the carbinyl proton is held more closely to the naphthyl ring, whereas in R,R)-28 its position is reversed. This situation results in the observed highfield sense of nonequivalence for the carbinyl proton of carbinols 27 and accounts for the opposite sense shown by the fluorine resonances. In one instance, aryl nonequivalence was also identified. AU three ring protons of trifluoromethyl-a-thienylcarbinol (13) show the same nonequivalence sense as the carbinyl proton (opposite to that of trifluoromethyl). Such also is expected from the proposed interactions 28, since the aryl substituent... 

Processes that enable direct catalytic C-C functionalization of carbinol C-H bonds are highly uncommon. Rh-catalyzed alcohol-vinylarene C-C coupling has been described. The requirement of BF3 and trends in substrate scope suggest these processes involve alcohol dehydrogenation-reductive Prins addition [26-29]. 

Moreover, octahydro compounds arise from the reduction (see Section 4.3) of higher unsaturated analogs, such as 8/9b/9d, 124a (see Scheme 32), 319a (see Scheme 71) or 374a and b (see Scheme 85), from the dehydration (see Section 4.4.3) of carbinol 24 or from the carbonylation (see Section 4.4.1) of enamine 133 (see Scheme 34). 

Other ester forming reactions lead to acetate 229b (61TH1), to the propionates of carbinols 24 and 331a (71JHC7, 76JPS1389), and to the... 

Further reactions of hydroxy groups involve the oxidation of carbinol 14a to ketone 15 (59AP143), oxidation and reduction of homoberbine epimers 167 to ketolactam 168 and lactam 170, respectively (71X1363), and dehydration of carbinol 24 (71JHC7). 

Repeated extraction is necessary in the cases of carbinols with a short carbon chain, alkoxy- or dialkylamino groups. 

Couplings of alkali acetylides with carbonyl compounds in liquid ammonia often give reduced yields. In many cases, the rates of carbinolate- and enolate formation (the alkali acetylide... 

In the case of carbinols from acetaldehyde and propionaldehyde, the Et20 should be distilled off at atmospheric pressure. 

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