Stereochemistry benzyl alcohols

Another effect of the coordination is that the benzylic cation is also stabilized [63]. This stabilization is explained by delocalization of the positive charge due to the interaction of the d-orbital of Cr with the 71-orbital of the benzylic carbon, caused by the coordination of Cr(CO)3. Facile stereospecific Friedel- Crafts-type cyclization of the complex of the optically active benzyl alcohol 248 gave the tetrahydrobenzazepine 249 with retention of the stereochemistry, and the free amine 250 with 98% ee was... 

Vertaline (61) was synthesized through two routes that involve an W-acylimin-ium ion cyclization (20) and an intermolecular [3 + 2] cycloaddition (21,22) as the key steps, respectively. Model studies (20, 24) for assembling the quinolizi-dine moiety by the W-acyliminium ion cyclization are shown in Scheme 7. The benzyl alcohol 65 was converted to glutarimide 66 by the Mitsunobu procedure in 55% yield. Reduction of imide 66 with diisobutylaluminum hydride afforded 67, which was subjected to V-acyliminium cyclization to give the lactam 68 in 40% overall yield from 66. Lactam 68 possesses the correct stereochemistry at all chiral centers required for vertaline (61). 

Intramolecular alkoxycarbonylation of secondary benzylic alcohols (e.g., 3) requires a shorter time (2 h) and a mixture of 1,3-disubstituted 3,4-dihydro-1 //-2-benzopyrans 4 is obtained in 82% yield and a 74 26 (cis/trans) diastereomeric ratio, as determined by HPLC. The stereochemistry of each isomer is determined by a comparison with known compounds84,85. 

Using a lead cathode in dilute methanolic sulfuric acid at constant current of 20 mAmp cm-2, the benzyl alcohol was the major product from an unstirred solution, while mechanical stirring reversed the position to favor the hydrodimer. However, ultrasonic irradiation from a cleaning bath (100 W, 36 kHz) so strongly favored the hydrodimer that the alcohol was barely evident. The effect varied somewhat with the position of the cell in the ultrasonic bath, and increased in magnitude with ultrasonic power, but throughout all electrolyses there was no appreciable change in the stereochemistry (dl/meso ratio) of the benzoin hydrodimer. 

Benzylic carbocations are also stabilized by complexation to chromium and a number of interesting reactions have been reported. Again, reaction of the carbocations with nucleophiles occurs from the exo face of the complex, relative to the metal. Carbocations are readily formed by treatment of benzylic alcohols with a strong acid, such as sulfuric acid, tetrafluoroboric acid, or borontrifluoride etherate. The cation can be trapped with water, alcohols, nitriles, and mono-or disubstituted amines to form alcohols, ethers, amides, and di- or trisubstituted amines respectively. Scheme 96 illustrates the formation of a benzylic carbocation followed by intramolecular trapping, resulting in a net inversion of stereochemistry. Benzylic acetates react with trimethyl aluminium introducing a methyl group from the opposite face of the metal. 

We thus postulated that the Adler-Becker oxidation could be used for this purpose (Figure 2). This approach would also benefit from the use of common intermediates previously synthesized during our Wessely oxidation campaign. Our new retrosynthetic route is outlined in Scheme 6 and apart from the key oxidative dearomatization step, it is identical to the previous one (Scheme 2). We envisioned that the more substituted site of the resulting epoxide could be selectively reduced after cycloaddition to reveal the desired C4-secondary alcohol found in vinigrol with correct stereochemistry. We were surprised to learn from the Adler-Becker oxidation literature that there were only a handful of examples employing secondary benzylic alcohols, and none of them were part of systematic studies in fact, the vast majority of published examples used only methylene alcohol derivatives as substrates. 

In 2014, Canesi s group also reported on a remarkable application of their chemistry that enabled them to develop an asymmetric synthesis of the tetracyclic main core of kaurane diterpenes [131]. The phenolic non-conjugated enyne 249 was elaborated to fulfill the reactivity and stereochemistry requirements of the intended oxidative cationic polycyclization [132], in tandem with apinacolic transposition. After chlorination of the benzylic alcohol of 249 with inversion of configuration, the use of BTI rapidly promoted this dearomative tandem process, which thus... 

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