Aldehydes hydrogenolysis

Oxidation of orixine with periodic acid gives acetone and an aldehyde hydrogenolysis of the ethylthioketal of the latter, followed by de-methjdation, yields LXXI which is identical with the hydrogenolysis product of kokusagine (138). 

The Pd-catalyzed hydrogenoiysis of acyl chlorides with hydrogen to give aldehydes is called the Rosenmund reduction. Rosenmund reduction catalyzed by supported Pd is explained by the formation of an acylpalladium complex and its hydrogenolysis[744]. Aldehydes can be obtained using other hydrides. For example, the Pd-catalyzed reaction of acyl halides with tin hydride gives aldehydes[745]. This is the tin Form of Rosenmund reduction. Aldehydes are i ormed by the reaction of the thio esters 873 with hydrosilanes[746,747]. 

Diaryl disulfides and diselenides add to alkynes to afford the (Z)-l, 2-bis(ar-ylthio)alkenes 193 and (Z)-l,2-bis(arylseleno)alkenes 194. Under CO pressure, carbonylative addition takes place to give thio esters and the selenoketones 195[I07], The selenoketones are converted into the /J-seleno-a, 3-unsaturated aldehydes 196 by Pd-catalyzed hydrogenolysis with HSnBu3[108,109],... 

Since hydrogenolysis resulted in only a 20% yield of the free aldehyde, a two-step procedure was developed in which the diphenylmethyl group was first cleaved with HF/anisole and then the unsubstituted semicarbazone was cleaved with formalin in 40-60% overall yield. 

Aldehydes and ketones are similar in their response to hydrogenation catalysis, and an ordering of catalyst activities usually applies to both functions. But the difference between aliphatic and aromatic carbonyls is marked, and preferred catalysts differ. In hydrogenation of aliphatic carbonyls, hydrogenolysis seldom occurs, unless special structural features are present, but with aryl carbonyls either reduction to the alcohol or loss of the hydroxy group can be achieved at will. 

Platinum, especially platinum oxide, has been used by many investigators (5), Platinum oxide, when used with aldehydes is apt to be deactivated before reduction is completed. Deactivation is inhibited by small amounts of ferrous or stannous chlorides (59,82). This type of promoter can also sharply curtail hydrogenolysis if it is a troublesome reaction (Rylander and Starrick, 1966). Deactivated systems can often be regenerated by shaking the reaction mixture with air (2,8,21 J3,96). The usefulness of this regenerative technique transcends aldehyde reductions it frequently is worth resorting to. 

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). 

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... 

On the other hand, syn-carboxylic acids are obtained from a deprotonation of the /5-silyl ester, giving the (E)-enolate, followed by reaction with different aldehydes and subsequent hydrogenolysis. No diastereomers of the aldol product are detected720. 

Selective Hydrogenolysis of Esters and Acids to Aldehydes and Alcohols... 

Hydrogenolysis of esters to aldehydes or alcohols needs high temperatures and high pressures. Moreover, it leads to the formation of acids, alcohols, and hydrocarbons. In contrast, bimetallic M-Sn alloys (M = Rh, Ru, Ni) supported on sihca are very selective for the hydrogenolysis of ethyl acetate into ethanol [181]. For example while the selectivity to ethanol is 12% with Ru/Si02, it increases up to 90% for a Ru-Sn/Si02 catalyst with a Sn/Ru ratio of 2.5 [182]. In addition, the reaction proceeds at lower temperatures than with the classical catalysts (550 K instead of temperatures higher than 700 K). The first step is the coordination of the ester to the alloy (Scheme 46), and most probably onto the tin atoms. After insertion into the M - H bond, the acetal intermediate decomposes into acetaldehyde and an ethoxide intermediate, which are both transformed into ethanol under H2. 

The key steps in the reaction are addition of hydridorhodium to the double bond of the alkene and migration of the alkyl group to the complexed carbon monoxide. Hydrogenolysis then leads to the aldehyde. 

Only scare data is available in the literature on the application of rhenium containing mono- or bimetallic catalysts in the hydrogenolysis of esters to alcohols. Decades ago Broadbent and co-workers studied the hydrogenation of organic carbonyl compounds (aldehydes, ketones, esters, anhydrides, acids,... 

Hydrogenolysis of an aldehyde or ketone carbonyl to >CH2 is an important organic transformation, and classical procedures such as the Clemmenson and Wolff-Kishner reactions have limitations (24, 25) heterogeneous catalytic systems and several two-step procedures are also known (1, 24, 26). Our observation of this conversion in what is essentially a 2-phase medium... 

The keto carbonyl group can be hydrogenated fairly readily and many of the characteristics of aldehyde hydrogenations also apply here. Initially, the alcohol is produced, but overhydrogenation may result in hydrogenolysis of the C-O bond to form the alkane (Fig. 2.23). Acidic media facilitate hydrogenolysis whereas basic media or basic substituents inhibit hydrogenolysis. 

Hydrogenolyses of carboxylic acids and esters to the corresponding aldehydes seems very attractive due to their simplicity. Copper chromites are the most widely used catalysts.15 Raney copper and zinc oxide-chromium oxide have also been used for this process.16-18 The hydrogenolysis of methyl benzoate to benzaldehyde was studied on various metal oxides at 300-350°C. ZnO, Zr02 and Ce02 presented high activities and selectivities (Scheme 4.8). 

Azaacetals Oxazolidines are formed from ethanolamines and aldehydes or ketones. The C-O bond in oxazolidines can be cleaved selectively by catalytic hydrogenolysis (Scheme 4.15). 

Hydrogenation of a C=0 double bond followed by catalytic hydrogenolysis of the resulting OH group is an alternative method for the conversion of aromatic aldehydes and ketones to alkanes. Pd/C and Pt02 are the most often used catalysts.49-51 In this way, dimethyltetralone was hydrogenated-hydrogenolyzed under 60 psi H2 for 5 hours in MeOH-HCl with 10% Pd/C (Scheme 4.22).52... 

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