Hydroxyl, hydrogenolysis

The blocking and deblocking of carboxyl groups occurs by reactions similar to those described for hydroxyl and amino groups. The most important protected derivatives are /-butyl, benzyl, and methyl esters. These may be cleaved in this order by trifluoroacetic acid, hydrogenolysis, and strong acid or base (J.F.W. McOmie, 1973). 2,2,2-Trihaloethyl esters are cleaved electro-lytically (M.F. Semmelhack, 1972) or by zinc in acetic acid like the Tbeoc- and Tceoc-protected hydroxyl and amino groups. 

For a ceUulosic material containing hydroxyl groups, the reactions might consist of dehydroxylation and depolymerization by hydrogenolysis, during which there is a transition from soHd to Hquid to gas. 

The nitrobenzyl caibonates were prepared to protect a secondary hydroxyl group in a thienamycin precursor. The o-nitrobenzyl carbonate was prepared from the chloroformate (DMAP, CH2CI2, 0° - 20°, 3 h) and cleaved by irradiation, pH 7. The p-nitrobenzyl carbonate was prepared from the chloroformate (—78°, n-BuLi, THE, 85% yield) and cleaved by hydrogenolysis (H2/Pd-C, dioxane, H2O, EtOH, K2HP04). It is also cleaved by electrolytic reduction. ... 

The 4-(dimethylaminocarbonyl)benzyl ether has been used to protect the phenolic hydroxyl of tyrosine. It is stable to CF3CO2H (120 h), but not to HBr/AcOH (complete cleavage in 16 h). It can also be cleaved by hydrogenolysis (H2/Pd-C). ... 

Isopropylidene and benzylidene" groups have been used to protect simultaneously amide nitrogens and a neighboring hydroxyl. They can be removed by acid hydrolysis or hydrogenolysis (Pd-C, hydrazine, MeOH, 95% yield), respectively. 

Aromatic rings are hydrogenated with a variety of catalysts. However, aromatic alkoxy and hydroxyl substituents are susceptible to hydrogenolysis under most conditions used to saturate the ring. Hydrogenolysis does not occur to any appreciable extent with ruthenium catalysts even though high temperatures and pressures are required. Thus, substituted phenols are... 

A benzyl carbonate was prepared in 83% yield from the sodium alkoxide of glycerol and benzyl chloroformate (20°, 24 h). It was also prepared by a lipase-catalyzed ester exchange with allyl benzyl carbonate. It is cleaved by hydrogenolysis (H2/Pd-C, EtOH, 20°, 2 h, 2 atm, 76% yield) and electrolytic reduction (—2.7 V, R4N X, DMF, 70% yield). A benzyl carbonate was used to protect the hydroxyl group in lactic acid during a peptide synthesis." ... 

Condensation of normeperidine (81) with 3-chloropropan-l-ol affords the compound possessing the alcohol side chain (88). The hydroxyl is then converted to chlorine by means of thionyl chloride (89) displacement of the halogen by aniline yields pimino-dine (90). ° Condensation of the secondary amine, 81, with styrene oxide affords the alcohol, 91 removal of the benzyllic hydroxyl group by hydrogenolysis leads to pheneridlne (92). ... 

Extreme differences between 5% palladium-on-carbon and platinum oxide were found on reduction of the 5-aryl substituted oxazole 14. Over palladium, 15 was formed in quantitative yield by hydrogenolysis of the benzyl hydroxyl, whereas over Pt, scission of the oxazole occurred to give 13 quantitatively (48). Hydrogenation of 15 over platinum oxide gave the phenethylamide 16. 

From intermediate 28, the construction of aldehyde 8 only requires a few straightforward steps. Thus, alkylation of the newly introduced C-3 secondary hydroxyl with methyl iodide, followed by hydrogenolysis of the C-5 benzyl ether, furnishes primary alcohol ( )-29. With a free primary hydroxyl group, compound ( )-29 provides a convenient opportunity for optical resolution at this stage. Indeed, separation of the equimolar mixture of diastereo-meric urethanes (carbamates) resulting from the action of (S)-(-)-a-methylbenzylisocyanate on ( )-29, followed by lithium aluminum hydride reduction of the separated urethanes, provides both enantiomers of 29 in optically active form. Oxidation of the levorotatory alcohol (-)-29 with PCC furnishes enantiomerically pure aldehyde 8 (88 % yield). 

The completion of the synthesis of gilvocarcin V (2) only requires a few functional group manipulations. Hydrogenolysis of the four benzyl groups, followed by acetylation of the liberated hydroxyl groups, provides 30 in 68 % overall yield. After cleavage of the MOM ether in 30 with bromotrimethylsilane, application... 

We now tum our attention to the C21-C28 fragment 158. Our retrosynthetic analysis of 158 (see Scheme 42) identifies an expedient synthetic pathway that features the union of two chiral pool derived building blocks (161+162) through an Evans asymmetric aldol reaction. Aldehyde 162, the projected electrophile for the aldol reaction, can be crafted in enantiomerically pure form from commercially available 1,3,4,6-di-O-benzylidene-D-mannitol (183) (see Scheme 45). As anticipated, the two free hydroxyls in the latter substance are methylated smoothly upon exposure to several equivalents each of sodium hydride and methyl iodide. Tetraol 184 can then be revealed after hydrogenolysis of both benzylidene acetals. With four free hydroxyl groups, compound 184 could conceivably present differentiation problems nevertheless, it is possible to selectively protect the two primary hydroxyl groups in 184 in... 

The oxirane ring in 175 is a valuable function because it provides a means for the introduction of the -disposed C-39 methoxy group of rapamycin. Indeed, addition of CSA (0.2 equivalents) to a solution of epoxy benzyl ether 175 in methanol brings about a completely regioselective and stereospecific solvolysis of the oxirane ring, furnishing the desired hydroxy methyl ether 200 in 90 % yield. After protection of the newly formed C-40 hydroxyl in the form of a tert-butyldimethylsilyl (TBS) ether, hydrogenolysis of the benzyl ether provides alcohol 201 in 89 % overall yield. 

Hydrogenolysis of the C-7 benzyl ether, followed sequentially by selective triethylsilylation of the newly liberated C-7 hydroxyl and mesylation of the C-5 secondary hydroxyl, provides compound 34 in 60% overall yield (see 33—>34, Scheme 6). On the basis of Potier s studies,35 it was hoped that the C 20 hydroxyl group,... 

Polyhydric Alcohols. (Polyols). An alcohol with three or more hydroxyl groups, each attached to a different carbon atom. They are w-sol and of sweetish taste, which tends to intensify with increasing hydroxyl content. Examples of polyols of ordn interest are listed below. Polyvinyl alcohol is considered in a separate entry as a polymer although it is defined as a polyhydric alcohol. Polyols, when nitrated, make excellent expls, proplnt binders, plasticizers, etc. Prepn can follow the procedure of Lenth DuPuis (Ref 3) which uses a methanol suspension of either sucrose or dextrose and a special Cu-Al oxide catalyst to yield 60-65% distillable polyols at 240° and 1500psi Refs 1) Beil — refs found under individual compds 2) CA, under Alcohols, Polyhydric for compds of current ordn interest 3) C.W. Lenth R.N. DuPuis, "Polyhydric Alcohol Production by Hydrogenolysis of Sugars in the Presence of Copper-Aluminum Oxide , IEC 37, 152-57 (1945) CA 39, 1391 (1945)... 

Hydrogenolysis. Hydrogenation of polycyclopropanone was carried out using supported catalysts. Before hydrogenation was attempted the polymers were end-capped in a refluxing mixture of acetic anhydride and pyridine. This was done to convert thermally unstable hydroxyl end groups, which may have been present in the polymer, to more thermally stable acetyl end groups as shown in Equation 8. This was... 

The same corynoline analog (214) was obtained more conveniently through photolysis in the presence of nitrosobenzene. Addition of nitrosobenzene to 208 from the opposite side of the methyl group resulted in the B/C-trans adduct 215. Reduction of 215 with sodium borohydride followed by acidic treatment gave the B/C-cis product 217 via 216. Hydroxylation of 217 with performic acid and hydrogenolysis of the diol 218 completed the synthesis of 214 (126). 

The 8-methyl-8,14-cycloberbine 364, derived from the protoberberine 324 via the betaine 363, was reduced with sodium borohydride or lithium aluminum tri-tert-butoxyhydride to give a diastereoisomeric mixture of cis-and trans-alcohols (7.8 1 or 1 7.8, respectively) (Scheme 64).t)n exposure to formaldehyde the mixture underwent N-hydroxymethylation and subsequent intramolecular substitution on the aziridine ring to give the oxazolidine 365. Removal of the hydroxyl group in 365 was accomplished by chlorination followed by hydrogenolysis with tributyltin hydride. Reductive opening of the oxazolidine 366 with sodium cyanoborohydride afforded ( )-raddeanamine (360), which has already been converted to ochotensimine (282) by dehydration. 

Hydrogenation of carbonyl groups occurs readily over most catalysts.144 However, care must be exercised in preventing hydrogenolysis of the resulting hydroxyl group. 

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