Reactions reductive benzylization

However, none of these compounds can be easily resolved except TM (16) Itself. Me prefer to resolve as early as possible, (page T 94), so It is better to carry out the Diels-Alder reaction with acrylic acid and resolve acid (19) before adding the phenyl group by a Grignard reaction. The benzylic alcohol group in (20) can be taken out by metal-anunonia reduction. Syrithesis ... 

Reaction of allyl nalides with the iron powders is rapid and exothermic and leads to near quantitative yields of the self-coupled product 1,5-hexadiene. Similarly, reaction of benzyl chloride with the iron powders at room temperature yields bibenzyl in 60-70% yields along with 20-25% of toluene. In contrast, reaction of aryl halides with the iron powders leads to reductive cleavage rather than self-coupling. Similarly, reaction of 1-bromoheptane with the iron powder in THF for three hours at room... 

BINAL-H reagents 45 are not effective in the enantioselective reduction of dialkyl ketones.53 For example, reaction of benzyl methyl ketone with (S)-45 gives (S )-l-phenyl-2-propanol in only 13% ee (71% yield). Reaction of 2-octanone with (R)-45 produces (S )-2-octanol in 24% ee (67% yield).53 This drop of ee values in the reaction may be explained by the lower energy difference between the favored transition state 48 and unfavored transition state 49 caused by the lack of the above-mentioned n-n repulsion between the reductant and the substrate dialkyl ketone. 

FIGURE 3.4 Deprotection of functional groups by reduction with sodium in liquid ammonia [du Vigneaud et al., 1930]. As in Figure 3.3, except reduction is effected by solvated electrons and protons are provided by water at the end of the reaction. Excess sodium is destroyed by NH4C1. This is a simplified presentation of the reaction. AH benzyl-based protectors as well as -Arg(N02)-, -Arg(Tos)-, and -His(Tos)- are sensitive to sodium in liquid ammonia. 

Figure 10. Cyclic voltammetric response at the NPyeCME for the oxidation/ reduction reaction of benzyl alcohol (32 mM)/C10 in aqueous 4.1 mol NaOCl (A) and nonaqueous CH2CI2 (B) solutions at a scan rate of 50 mV/s. (C) Cartoon for the NPyeCME. Inset (A) corresponds to an enlarged version of the oxidation part without (a) and with (b) benzyl alcohol. In order to marntam the electrical conductivity, 0.1 M tetrabutylammonium bromide (TBAB) is added into the CH2CI2 solution.

Benzyltriazoles are readily available through cycloaddition reactions of benzyl azide. The benzyl group can be removed by reduction with... 

Reaction of benzyl a-D-glucopyranosyl cyclic sulfate 44 or benzyl a-D-galactopyranosyl cyclic sulfate 45 with 1,4-anhydro-2,3,5-tri-0-benzyl-4-thio-D-arabinol 46, followed by debenzylation and reduction, gave novel sulfonium sulfate derivatives 47a and 47b, respectively, which were used to prepare homologs of salacinol 48, a natural human maltase glucoamylase inhibitor, as lead candidates for the treatment of type 2 diabetes (Scheme 3) <2006JOC1111>. 

Phenylacetamide has been obtained by a wide variety of reactions from benzyl cyanide with water at 250-260° 6 from benzyl cyanide with water and cadmium oxide at 240° 6 from benzyl cyanide with sulfuric acid 7 8 by saturation of an acetone solution of benzyl cyanide with potassium hydrosulfide 9 from benzyl cyanide with sodium peroxide 10 by electrolytic reduction of benzyl cyanide in sodium hydroxide 11 from ethyl phenyl-acetate with alcoholic 12 or aqueous 13 ammonia from phenyl-acetic acid with ammonium acetate 14 or urea 15 from diazoacetophenone with ammoniacal silver solution 16 from phenyl-acetic acid imino ether hydrochloride and water 17 from acetophenone with ammonium poly sulfide at 215° 18 from benzoic acid 19 and by heating the ammonium salt of phenyl-acetic acid.20... 

Direct reduction of an aldehyde or ketone to the corresponding ether could potentially telescope two reactions, reduction and protection, into one step. S. Chandrasekhar of the Indian Institute of Chemical Technology, Hyderabad, reports (Tetrahedron Lett. 2004,45,5497) that in the present of polymethylhydrosiloxane (PMHS) and catalytic B(C6F,), TMS ethers of alcohols will convert aldehydes to the corresponding dialkyl ethers. The reaction works well for both saturated and benzylic alcohols. This may prove to be a useful alternative to Williamson synthesis for the preparation of complex ethers. 

A further example of an imbalance reduction is seen in the reaction 1-benzyl-l-methoxy-2-nitroethylenes (47-Z) with secondary alicyclic amines in 50% DMSO-50% water (v/v).103... 

An example is the preparation of the unsaturated alcohol 42 whose benzyl ether was needed for a Diels-Alder reaction. Reduction of the diene ester 43 with LiAltLj gave 85% of the alcohol. The starting material 43 is easily made9 by methods discussed in chapters 15 and 19. 

The alcohol product can be formed by reduction of a carboxylic acid with UAIH4. The carboxylic acid can be synthesized either by Grignard carboxylation or by nitrile hydrolysis. The product can also be formed by a Grignard reaction between benzyl bromide and formaldehyde. 

Mechanism was first discussed of the reaction with benzylic and aryl haUdes in 1979 [8,9]. As shown in other protocols, the three-step catalytic cycle is widely accepted, that is, oxidative addition, transmetallation, and reductive elimination (Scheme 5). 

Cyclizations by formation of carbon—selenium bonds represent a modern method with a high synthetic potential in the chemistry of cyclophanes. Selenocyanates such as 16 are accessible usually in excellent yields through the reaction of bromides with KSeCN [27], The reaction with benzylic bromides under reductive conditions using the dilution principle results in good to excellent yields of [3.3]di-selenacyclophanes which can be deselenized photochemically, pyrolytically (without previous oxidation), or by reaction with arynes, Stevens rearrangement and subsequent reaction with Raney nickel. [2.2]Metacyclophane (18), for example, is accessible in 47% total yield by using this sequence of reactions starting with... 

Sonochemistry has been applied to acceleration of the Reformatsky reaction, Diels-Alder reactions, the arylation of active methylene compounds nucleophilic aromatic substitution of haloarenes, and to hydrostannation and tin hydride reduction. " Other sonochemical applications involve the reaction of benzyl chloride and nitrobenzene, a Sr I reaction in liquid ammonia at room temperature, and Knoevenagel condensation of aromatic aldehydes. lodination of aliphatic hydrocarbons can be accelerated, and oxyallyl cations have been prepared from ot,ot -diiodoketones using sonochemistry. Sonochemistry has been applied to the preparation of carbohydrate compounds.When sonochemistry is an important feature of a chemical reaction, this fact will be noted in the reactions presented in Chapters 10-19. 

Potassium diphenylarsenide-2-dioxane reacts with (—)-menthyl chloride in boiling tetrahydrofuran to give (lS,2S,5i )-( + )-neomenthyldiphenylarsine, (S)-( + )-175 (neo-menars). The arsine was obtained as colourless needles in ca 40% yield after recrystallization from warm methanol (Table 9). The neomenthylarsine, upon reaction with benzyl bromide in benzene, affords the epimeric (li ,2S,5i )-benzylmenthylarsonium bromide, (i H-f-)-176, which, upon reduction with lithium aluminium hydride, affords (l/t,2S,5K)-diphenylmenthylarsine, (J )-( — )-177 (menars) (equation 25). 

It is of interest that a dihydroisoquinoline like 3,4-dihydropapaverine is more easily reducible than the parent compound [268] the electrode reaction is saturation of the azomethine bond. 3,4-Dihydro-2-alkylisoquinolinium salts may be reductively benzylated at C-1 [17] in aprotic media. 

---