Allylic alcohol, reduction with lithium

Vinylogs of benzylic alcohols, e.g. cinnamyl alcohol, undergo easy saturation of the double bond by catalytic hydrogenation over platinum, rhodium-platinum and palladium oxides [39] or by reduction with lithium aluminum hydride [609]. In the presence of acids, catalytic hydrogenolysis of the allylic hydroxyl takes place, especially over platinum oxide in acetic acid and hydrochloric acid [39]. 

These data indicate a close relationship with ajmalicine, which is supported by chemical evidence. Thus, selenium dehydrogenation gives alstyrine lithium aluminum hydride reduction gives a primary alcohol, akuammigol (I), which possesses a typical indole UV-spectrum, with a deep minimum at 250 m/r. The formulation of this product as an allylic alcohol, stereoisomeric with tetrahydroalstonol, is further shown by its... 

Reaction of allylic alcohol 396 with paraformaldehyde using a catalytic amount of p-toluenesulfonic acid gave cyclic carbamate 397, which upon reduction with lithium aluminum hydride afforded aminodiol 398. Oxidative cleavage of the double bond of 398, achieved by dry silica gel ozonization (80JA5968) of the trifluoro acetate salt of aminodiol 398, gave ( )-5-epi-desosamine (399) (Scheme 49). 

Selective oxidation of an allylic secondary alcohol group without attack of saturated secondary alcohol groups was demonstrated by Mancera, Rosenkranz, and Sondheimer. Adrenosterone (I) on reduction with lithium aluminum hydride... 

The allylic alcohol of 9 was converted to the chloride 10 and coupled with the thioether anion of previously synthesized triene 11 (Scheme 2). The compound 12 now has all 30 carbons, and five double bonds, of squalene epoxide. Reduction with lithium in ethylamine removed the thioether activating group... 

Reduction with lithium aluminium hydride-aluminium chloride (3 1) provides a good route from a,(3-unsaturated carbonyl compounds to unsaturated alcohols (or amines), which are difficult to prepare with lithium aluminivun hydride alone because of competing reduction of the carbon-carbon double bond. For example, a,p-unsaturated esters are reduced to allylic alcohols, although diisobutyla-luminium hydride (DIBAL-H) is normally the reagent of choice for this transformation. Reduction of carboxylic amides can sometimes be preferable using AIH3 (7.78). 

The synthesis of the trisubstituted cyclohexane sector 160 commences with the preparation of optically active (/ )-2-cyclohexen-l-ol (199) (see Scheme 49). To accomplish this objective, the decision was made to utilize the powerful catalytic asymmetric reduction process developed by Corey and his colleagues at Harvard.83 Treatment of 2-bromocyclohexenone (196) with BH3 SMe2 in the presence of 5 mol % of oxazaborolidine 197 provides enantiomeri-cally enriched allylic alcohol 198 (99% yield, 96% ee). Reductive cleavage of the C-Br bond in 198 with lithium metal in terf-butyl alcohol and THF then provides optically active (/ )-2-cyclo-hexen-l-ol (199). When the latter substance is treated with wCPBA, a hydroxyl-directed Henbest epoxidation84 takes place to give an epoxy alcohol which can subsequently be protected in the form of a benzyl ether (see 175) under standard conditions. 

The stereochemistry of the first step was ascertained by an X-ray analysis [8] of an isolated oxazaphospholidine 3 (R = Ph). The overall sequence from oxi-rane to aziridine takes place with an excellent retention of chiral integrity. As the stereochemistry of the oxirane esters is determined by the chiral inductor during the Sharpless epoxidation, both enantiomers of aziridine esters can be readily obtained by choosing the desired antipodal tartrate inductor during the epoxidation reaction. It is relevant to note that the required starting allylic alcohols are conveniently prepared by chain elongation of propargyl alcohol as a C3 synthon followed by an appropriate reduction of the triple bond, e. g., with lithium aluminum hydride [6b]. 

Unlike with sodium borohydride (see Section 11.01.5.2), pyrrolizin-3-one 2 reacts with lithium aluminohydride mainly as an amide. No conjugate addition occurs, and only the reductive lactam cleavage takes place to give stereoselectively the (Z)-allylie alcohol 77. Similarly, benzo-annulated pyrrolizin-3-one 17 gives the corresponding benzylic alcohol 78. The same reactivity was observed with organometallics such as methyllithium which gives exclusively the tertiary (Z)-allylic alcohol 79 (Scheme 7). 

Results of the reduction of unsaturated alcohols depend on the respective positions of the hydroxyl and the double bond. Since the hydroxyl group is fairly resistant to hydrogenolysis by catalytic hydrogenation almost any catalyst working under mild conditions may be used for saturation of the double bond with conservation of the hydroxyl [608]. In addition, sodium in liquid ammonia and lithium in ethylamine reduced double bonds without affecting the hydroxyl in non-allylic alcohols [608]. 

Replacement of an allylic hydroxyl without saturation or a shift of the double bond was achieved by treatment of some allylic-type alcohols with triphenyliodophosphorane (PhjPHI), triphenyldiiodophosphorane (PhsPIj) or their mixture with triphenyl phosphine (yields 24-60%) [612]. Still another way is the treatment of an allylic alcohol with a pyridine-sulfur trioxide complex followed by reduction of the intermediate with lithium aluminum hydride in tetrahydrofuran (yields 6-98%) [67 J]. In this method saturation of the double bond has taken place in some instances [675]. 

Chiral allylic alcohols.1 Desulfuration of the (3-hydroxy sulfoxides 1 with Raney nickel (11, 292) proceeds with simultaneous reduction of the double bond, but can be effected selectively with lithium in ethylamine at - 78° to give optically active allylic alcohols (2). 

The propargylic alcohol group may be exploited as an allylic alcohol precursor (Eq. 6A.2) and may be generated by nucleophilic addition to an electrophile [25] or by addition of a formaldehyde equivalent to a preexisting terminal acetylene group [26], Once in place, reduction of the propargylic alcohol with lithium aluminum hydride or, preferably, with sodium bis(2-methoxyethoxy)aluminum hydride (Red-Al) [27] will produce the trans allylic alcohol. Alternately, catalytic reduction over Lindlar catalyst can be used to obtain the cis allylic alcohol [28]. The addition of other lithium acetylides to ketones produces chiral secondary alcohols, which also can be reduced by the preceding methods to the cis or trans allylic alcohols. Additional synthetic approaches to allylic alcohols may be found in the various references cited in this chapter. 

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