Diastereoselective synthesis hydrogenation

An important example of heterogeneous diastereoselective synthesis by catalytic way is the synthesis of prostaglandines (a family of compounds having the 20-carbon skeleton of the prostanoic acid) (Scheme 14.14). Naturally, these molecules are biosynthesized via a cyclooxygenase enzyme system that is widely distributed in mammalian tissues. Many of the synthetic routes [272] involve the diastereoselective hydrogenation of a carbonylic bond having a C=C double bond... 

Urea 32, the bis-(mono-trifluoromethyl)phenyl derivative of urea catalyst 16 [178], was reported to operate as double hydrogen-bonding organocatalyst in the diastereoselective synthesis of y-butenolide products substituted at the y-position... 

The catalyzed hydrogenation of alkenylboronic esters was used for the diastereoselective synthesis of alkylboronic esters 276446 (Equation (75)). The hydrogenation of a pyrrolboronic acid provided a prolineboronic acid, which was then resolved by HPLC to give an optically active boronic ester 277447 (Equation (76)). 

R)-(-)-2,2-Diphenylcyclopentanol (1) is a highly effective chiral auxiliary in asymmetric synthesis. Hydrogenation of chiral 0-acetamidocrotonates derived from this alcohol has afforded the corresponding 0-amido esters with high diastereoselectivity (96% de).6 In addition, (R)-1 has been used as a chiral auxiliary in Mn(lll)-based oxidative free-radical cyclizations to provide diastereomerically enriched cycloalkanones (60% de).7 Our interest in (R)-(-)-2,2-diphenylcyclopentanol is its utility as a chiral auxiliary in Lewis acid-promoted, asymmetric nitroalkene [4+2] cycloadditions. The 2-(acetoxy)vinyl ether derived from alcohol (R)-1 is useful for the asymmetric synthesis of 3-hydroxy-4-substituted pyrrolidines from nitroalkenes (96% ee).8 In a similar fashion, a number of enantiomerically enriched (71-97% ee) N-protected, 3-substituted pyrrolidines have been prepared in two steps from 2-substituted 1-nitroalkenes and (R)-2,2-diphenyl-1-ethenoxycyclopentane (2) (see Table).9... 

For complexes of type 10 (with a hydrogen at the carbene carbon) a synthesis was worked out in which a formamide is first reacted with K2[Cr(CO)j] followed by reaction with TMSCI [7]. This way, the non-racemic formamide 12 leads to the chirally modified amino carbene complex 13, which serves as starting material for the diastereoselective synthesis of various optically active yff-lactams [8]. An example is the (formal) total synthesis of 1-carbacephalothin 16, a carbon analog of the cephalosporins (Scheme 5) [8b]. In this case, the complex 13 is irradiated in the presence of in situ prepared imine 14 to afford the /(-lactam with high dia-stereoselectivity but only in modest yield. The product (15) could (in principle) be converted in to the target compound 16. 

In many cases various proton sources, solvents, auxiliaries, and conditions have been applied in order to obtain different diastereoselectivites from the protonation of nonstereogenic car-banion centers. However, only the tw o extreme diastereomeric product ratios are given in this section. In most experiments kinetically controlled protonation can be assumed. However, since the anionic substrate already carries one (or more) stereogenic center, selective equilibration at the newly formed stereogenic carbon - hydrogen center could increase the diastereoselec-tivity. Indeed, epimerization of this center is a valuable tool for diastereoselective synthesis, provided that the carbon-hydrogen bond is acidic enough (see enolates, Section 2.1.3.1). 

The first diastereoselective synthesis of methyl (3R,7R)-jasmonate is attributed to Gerhard Quinkert. [94] In the initial step, starting from bis-(8-phenyhnen-thyl) malonate, a vinylcydopropane is constructed. After removal of the chiral auxiliary, the cyclopentanone is built up by means of a domino homo-Michael reaction / Dieckmann cydisation. Attack of dimethyl pent-2-ynylmalonate leads to inversion at the stereogenic centre at the vinyl cyclopropane. After decarboxylation, the vinyl residue is transformed into an ester group and the triple bond hydrogenated with a Lindlar catalyst. 

Scheme 57 Diastereoselective transfer hydrogenation in the formal total synthesis of (-)-platensimycin (245)...

The scope of the ruthenium-catalysed asymmetric transfer hydrogenation methodology was very recently extended to a-alkyl-substituted )S-ketoamides by Limanto et Indeed, the first enantio- and diastereoselective synthesis of various syn a-alkyl-substituted jS-hydroxyamides via highly efficient Ru-cata-lysed hydrogenation through DKR of the corresponding ) -ketoamides has been successfully demonstrated. As shown in Scheme 2.31, excellent diastereo-and enantioselectivities of up to 98% de and > 99% ee, respectively, were observed when the process was performed in CH2CI2 or toluene as the solvent. 

The Strecker reaction of a dial with an amine and hydrogen cyanide, to produce a cyclic a,a -dicyanoamine, involves HCN addition to a cycUc imino nitrile intermediate as the final step. A highly diastereoselective synthesis of dihydro-5//-dibenz[c, ]azepines (80) from the biphenyldicarboxaldehyde exploits the chiral twist of the biaryl axis to achieve stereoselection. ... 

MUiovQovic MD, Spreitzer H (2005) Diastereoselective synthesis of ds-2,6-disubstituted per-hydro-4-pyranones using elevated pressure hydrogenation. Monatsh Chem 136 1197-1203... 

SCHEME 5.6. Microwave-assisted diastereoselective synthesis of a 4-spiro-pyrazolidin-3-one via a hydrazone formation/Wolff rearrangement/l,2-hydrogen shift/l,3-dipolar cycloaddition domino sequence. 

The cobalt-catalyzed [2+2+2] cycloaddition of 4-hydroxy-substituted enediynes [152] that has been implemented in the synthesis of 2-hydroxy substituted decahydrophenanthrenes [153] has shown that the hydroxy group in the propargyl position tolerates the chosen reaction conditions. So, this approach could be an appropriate route to hydrogenated trans-phenanthrenes, which are the ABC cores of ergosterin and lumisterin steroids. This was a reason to consider the diastereoselective synthesis of (3S)-hydroxyandrosta-5,7-diene-17-ones 2.307, the precursors of vitamin D, via a D ABCD approach. 

Asymmetric synthesis is a method for direct synthesis of optically active amino acids and finding efficient catalysts is a great target for researchers. Many exceUent reviews have been pubHshed (72). Asymmetric syntheses are classified as either enantioselective or diastereoselective reactions. Asymmetric hydrogenation has been appHed for practical manufacturing of l-DOPA and t-phenylalanine, but conventional methods have not been exceeded because of the short life of catalysts. An example of an enantio selective reaction, asymmetric hydrogenation of a-acetamidoacryHc acid derivatives, eg, Z-2-acetamidocinnamic acid [55065-02-6] (6), is shown below and in Table 4 (73). 

Lewis acids, results in the formation of isopulegol (43) with greater than 98% diastereoselectivity isopulegol (43), wherein all of the ring substituents are equatorially oriented, arises naturally from a chairlike transition state structure in which the C-3 methyl group, the coordinated C-l aldehyde carbonyl, and the A6,7 double bond are all equatorial (see 48). A low-temperature crystallization raises the chemical and enantiomeric purity of isopulegol (43) close to 100%. Finally, hydrogenation of the double bond in 43 completes the synthesis of (-)-menthol (1). 

It is important to emphasize that the hydroxy dithioketal cyclization can be conducted under mild reaction conditions and can be successfully applied to a variety of substrates.15 However, the utility of this method for the synthesis of didehydrooxocane-contain-ing natural products requires the diastereoselective, reductive removal of the ethylthio group. Gratifyingly, treatment of 13 with triphenyltin hydride and a catalytic amount of the radical initiator, azobisisobutyronitrile (AIBN), accomplishes a homolytic cleavage of the C-S bond and furnishes didehydrooxocane 14 in diastereo-merically pure form (95 % yield), after hydrogen atom transfer. 

An efficient stereoselective Strecker synthesis of phenylglycine has been achieved using the tert-butyl ester tm-leucine as the chiral auxiliary. Its benzaldimine reacts with hydrogen cyanide in hexane at — 23 °C to furnish the ( )-diastereomer with the excellent diastereoselectivity of >98 254. 

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