Lithium aluminum hydride stereochemistry

Some instances of incomplete debromination of 5,6-dibromo compounds may be due to the presence of 5j5,6a-isomer of wrong stereochemistry for anti-coplanar elimination. The higher temperature afforded by replacing acetone with refluxing cyclohexanone has proved advantageous in some cases. There is evidence that both the zinc and lithium aluminum hydride reductions of vicinal dihalides also proceed faster with diaxial isomers (ref. 266, cf. ref. 215, p. 136, ref. 265). The chromous reduction of vicinal dihalides appears to involve free radical intermediates produced by one electron transfer, and is not stereospecific but favors tra 5-elimination in the case of vic-di-bromides. Chromous ion complexed with ethylene diamine is more reactive than the uncomplexed ion in reduction of -substituted halides and epoxides to olefins. ... 

The success of the halo ketone route depends on the stereo- and regio-selectivity in the halo ketone synthesis, as well as on the stereochemistry of reduction of the bromo ketone. Lithium aluminum hydride or sodium borohydride are commonly used to reduce halo ketones to the /mm-halohydrins. However, carefully controlled reaction conditions or alternate reducing reagents, e.g., lithium borohydride, are often required to avoid reductive elimination of the halogen. 

Reduction of 3-methyl-4(3H)quinazolinone with lithium aluminum hydride is known to give 3-methyl-l,2,3,4-tetrahydroquinazoline. The most interesting tetrahydroquinazoline is Trbger s base ° since it has added to our knowledge of the stereochemistry of tri-... 

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]. 

Double bonds conjugated with benzene rings are reduced electrolytically [344] (p. 23). Where applicable, stereochemistry can be influenced by using either catalytic hydrogenation or dissolving metal reduction [401] (p. 24). Indene was converted to indane by sodium in liquid ammonia in 85% yield [402] and acenaphthylene to acenaphthene in 85% yield by reduction with lithium aluminum hydride in carbitol at 100° [403], Since the benzene ring is not inert toward alkali metals, nuclear reduction may accompany reduction of the double bond. Styrene treated with lithium in methylamine afforded 25% of 1-ethylcyclohexene and 18% of ethylcyclohexane [404]. 

The cyclic borates (758) are useful alternatives to benzanilides in the photochemical synthesis of phenanthridines. Irradiation, followed by reduction with lithium aluminum hydride, gives phenanthridines in good yield, the borate ring maintaining the correct stereochemistry (78CC884). 

Reactions of propynyl alcohols and their derivatives with metal hydrides, such as lithium aluminum hydride, constitute an important regio- and stereoselective approach to chiral allenes of high enantiomeric purity63-69. Formally, a hydride is introduced by net 1,3-substitution, however, when leaving groups such as amines, sulfonates and tetrahydropyranyloxy are involved, it has been established that the reaction proceeds by successive trans-1,2-addition and preferred anti-1,2-elimination reactions. The conformational mobility of the intermediate results in both syn- and ami- 1,2-elimination, which leads to competition between overall syn- and anti-1,3-substitution and hence lower optical yields and/or a reversal of the stereochemistry. 

Reduction of 3-trimethyls1lyl-2-propyn-l-ol exemplifies the problem of stereoselectivity in hydride reduction of acetylenic alcohols to E-allyl alcohols.4 Early reports5 that lithium aluminum hydride stereoselectively reduced acetylenic alcohols gave way to closer scrutiny which revealed a striking solvent dependence of the stereochemistry. Specifically, the... 

The main methods of reducing ketones to alcohols are (a) use of complex metal hydrides (b) use of alkali metals in alcohols or liquid ammonia or amines 221 (c) catalytic hydrogenation 14,217 (d) Meerwein-Ponndorf reduction.169,249 The reduction of organic compounds by complex metal hydrides, first reported in 1947,174 is a widely used technique. This chapter reviews first the main metal hydride reagents, their reactivities towards various functional groups and the conditions under which they are used to reduce ketones. The reduction of ketones by hydrides is then discussed under the headings of mechanism and stereochemistry, reduction of unsaturated ketones, and stereochemistry and selectivity of reduction of steroidal ketones. Finally reductions with the mixed hydride reagent of lithium aluminum hydride and aluminum chloride, with diborane and with iridium complexes, are briefly described. 

The structure XXII for rhynehophylline has been confirmed, and the relative stereochemistry at C-15 and C-20 has been elucidated, by a total synthesis (80) of (+) JV-methylrhynchophyllane (XXVI) (Marion s N-methylisorhynchophyllane), which had been prepared earlier by methyl-ation of (iso)rhynchophyllane with sodium methoxide and methyl iodide (28). The lactone (XXVII) of threo-3,4-diethyl-5-hydroxyvaleric acid was converted by reaction with phosphorus pentachloride into the corresponding S-chloroacid chloride (XXVIII), which on treatment with methylaniline gave the anilide XXIX. Reduction of XXIX with lithium aluminum hydride gave the aldehyde XXX, which slowly reacted with... 

Final clarification of the structure of quinamine was accomplished on the one hand by the production of cinchonamine upon lithium aluminum hydride reduction of the base (6), and on the other hand by the reverse reaction brought about by peracid (18) (Chart I). The reduction is explicable via the ring chain tautomeric hydroxyindolenine (VIII), which is also the primary product of the peracid oxidation of cinchonamine [cf. oxidation of tetrahydrocarbazole (19)]. The oxidation is stereospecific, but the stereochemistry of the introduced C-7 hydroxyl is still unknown. 

The stereochemistry at positions 3,15, and 20 is preserved in alloyo-himbone (LXIV) and its reduction product, alloyohimbane (3a, 15a,20a-yohimbane, LXV), of which several syntheses have been reported (Volume VII, p. 58) (30). In a recent synthesis, tryptamine (XXVI) was condensed with 4-methoxyhomophthalic anhydride (LXVI) to the amide LXVII. This in the five stages shown was converted to LXVIII and the latter, through another series of reactions, converted to LXX consisting of two epimers which were separable. Tosylation of the hydroxyl and ultimate reduction with lithium aluminum hydride generated alloyohimbane (LXV) (31). 

The stereochemistry of the major adduct was elucidated by H NMR and by conversion to the known 3/i-nitrocholestane. The corresponding aziridine could not be prepared, since the reduction with lithium aluminum hydride or zinc gave 2-cholestene, and treatment with iron(II) sulfate and hydrochloric acid gave starting material only. 

The same photoaddition takes place with N-nitrosodimethylamine. The stereochemistry of both the Ar,Af-dimethyl-2-nitroso-1-cyclohexanamine and 2-[hydroxy(nitroso)amino]-AT V-di-methyl-l-cyclohexaneamine was established by reduction with lithium aluminum hydride and A -acetylation to give both rrans -/V-acctyl-/Vr, Ar-dimethyl-l,2-cyclohexanediamine ( H NMR). 

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