Via Catalytic Hydrogenolysis

FIGURE 10.2 A new route for the production of 2,3-butanediol (modified from Ge et al., 2011). 

---

Because of its anticipated easy removal via catalytic hydrogenolysis, we decided to see the application of (R)-phenylglycine amide as a chiral auxiliary in asymmetric synthesis. (Adapted from Boesten et ah, 2001)... 

The deprotection of the Cbz protected amino acid proceeds via a two step mechanism (Figure 1). The first step comprises the catalytic hydrogenolysis of the benzyloxy group of the Cbz-protected amino acid (1). Toluene (3) is formed from the O-benzyl group as well as an unstable carbamic acid intermediate (2). This intermediate decomposes to form the unprotected amino acid (4) and carbon dioxide (5). 

Replacement of the iodine substituent by a hydrogen atom was achieved via selective catalytic hydrogenolysis using 3% Pd/C in MeOH containing AcONa and traces of quinoline at room temperature and 1... 

In a similar manner, starting from 2-methylchloride-naphtho[l,8-de][l,2,3]triazine and magnesium, via a novel sonication-promoted Barbier reaction, an a-aminomethyl carbanion equivalent is generated which reacts in situ with a variety of carbonyl compounds. Subsequent catalytic hydrogenolysis of the triazine moiety yields the corresponding amines <00TL4685>. Sterically controlled regiospecific cyclization of aldose-5-ethyl-l,2,4-... 

But GO is also an archetype for more complex polyols. Catalytic hydrogenolysis of polyols leads to C-C and C-0 bond cleavage as well as activation via dehydrogenation of HCOH to C=0 sites (8, 9). With its three vicinal hydroxyl groups, and its two types of carbon atoms (all bearing hydroxyl functionalities) GO can serve as a simple model in which to study the competition between these processes. We aim to gain insight into the individual steps and apply that information to increase selectivity toward desired products. 

The diol (43) obtained from dihydroxylation of acrolein benzene-1,2-dimethanol acetal (entry 11) is a masked glyceraldebyde and has the potential to be a very useful synthon. Although the enantiomeric purity of the crude diol formed in this reaction is 84% ee, one recrystallization from ethyl acetate improves it to 97% ee in 55% recovery yield. The masked glyceraldehyde 43 is converted via the tosylate 44 to the masked glycidaldehyde 45 in an overall yield of 85%. Both these masked aldehydes are superior to the free aldehydes in terms of handling ease, stability, and safety. The aldehydes can be released from the acetal under the mild conditions of catalytic hydrogenolysis [45]. 

Catalytic hydrogenation of 119 afforded 120, which was converted to 57 by sequential reduction with LiAlH4, catalytic hydrogenolysis of the A-benzyl group, and cyclization via a Pictet-Spengler reaction. 

FNA was synthesized by reaction of /(-naltrexamine (48) with the monomethyl ester of fumaroyl chloride [79], Amine (48) was prepared first from naltrexone by reductive amination with sodium cyanoborohydride in the presence of ammonium acetate to give 6a- and 6/i-epimers (ratio ca. 2 1). Separation was achieved by fractional crystallization [83], An improved synthesis of (48) was reported via the dibenzyliminium salt of naltrexone (46 easily accessible from naltrexone and dibenzylamine) which was reduced with sodium cyanoborohydride to give exclusively the 6/i-epi-mer (47). Catalytic hydrogenolysis afforded /i-naltrexamine (Scheme 3.6) [84]. 

The diazomethane ring expansion, when applied to (+)-173, led to the formation of 175, which was converted via ketone (-)-176 into (-)-homobasketane (143) (Ci). A similar sequence of conversions, including a second diazomethane ring expansion, transformed (-)-176 to (-)-3,10-dehydroditwistane (C2) (144). Catalytic hydrogenolysis cleaved the strained central bonds of (-)-143 and (-)-144 furnishing (-)-methanotwistane (136) (Ci) and (-)-ditwistane (137), (C2) respectively (149). 

An early application of the Amadori rearrangement reaction was the synthesis of lactulose 51 (Scheme 15) [68]. Reaction of lactose 48 withp-toluidine in pyridine/acetic acid furnished the corresponding rearrangement product 49, which, after catalytic hydrogenolysis to 1-amino-1-deoxyketose 50 and subsequent deamination, gave ketose 51. This was the first alternative approach to lactulose, which had been synthesized via a Lobry de Bruyn - Alberda van Ekenstein rearrangement [69]. 

---