Diastereoselective hydrogenation stereochemistry

Diastereoselective Hydrogenation since -OH directs the H2, there is a possibility for control of stereochemistry - sensitive to H2 pressure catalyst cone, substrate cone, solvent. 

Another formal synthesis of (5 ,9. -(—)-indolizidine 223AB (1780), by Charette and colleagues, employed a valine-derived auxiliary as an amide-containing appendage in the pyridine (—)-1788 in order to control absolute stereochemistry (Scheme 225). An unusual cyclization mediated by trifluor-omethanesulfonic anhydride followed by addition ofpropylmagnesium chloride afforded the (fo)-bicyclic amidine (—)-1789. Diastereoselective hydrogenation over palladium on carbon produced the saturated indolizidine (—)-1790, which was alkylated with iodomethane to give the amidinium salt... 

Modest diastereoselectivity was observed for the Michael addition reaction of rac-14 to 13 and these diasteromers 28-a/28-b could be separated and individually identified. The minor isomer 28-b was found to readily undergo conversion to benzoxathiin 30 when treated with BF3 etherate, presumably through the transient intermediate 29-b. The major isomer 28-a was converted by BF3 etherate to intermediate 29-a. Conversion to 30 required the use of the stronger Lewis acid TMSOTf, presumably due to the cis-stereochemistry between the methoxy and the neighboring hydrogen, making it more difficult to eliminate/aromatize. 

Iridium-catalyzed transfer hydrogenation of aldehyde 73 in the presence of 1,1-dimethylallene promotes tert-prenylation [64] to form the secondary neopentyl alcohol 74. In this process, isopropanol serves as the hydrogen donor, and the isolated iridium complex prepared from [Ir(cod)Cl]2, allyl acetate, m-nitrobenzoic acid, and (S)-SEGPHOS is used as catalyst. Complete levels of catalyst-directed diastereoselectivity are observed. Exposure of neopentyl alcohol 74 to acetic anhydride followed by ozonolysis provides p-acetoxy aldehyde 75. Reductive coupling of aldehyde 75 with allyl acetate under transfer hydrogenation conditions results in the formation of homoallylic alcohol 76. As the stereochemistry of this addition is irrelevant, an achiral iridium complex derived from [Ir(cod)Cl]2, allyl acetate, m-nitrobenzoic acid, and BIPHEP was employed as catalyst (Scheme 5.9). 

In the case of tri-substituted alkenes, the 1,3-syn products are formed in moderate to high diastereoselectivities (Table 21.10, entries 6—12). The stereochemistry of hydrogenation of homoallylic alcohols with a trisubstituted olefin unit is governed by the stereochemistry of the homoallylic hydroxy group, the stereogenic center at the allyl position, and the geometry of the double bond (Scheme 21.4). In entries 8 to 10 of Table 21.10, the product of 1,3-syn structure is formed in more than 90% d.e. with a cationic rhodium catalyst. The stereochemistry of the products in entries 10 to 12 shows that it is the stereogenic center at the allylic position which dictates the sense of asymmetric induction... 

A diastereoselective Mukaiyama aldol lactonization between thiopyridylsilylketene acetals and aldehydes was used to form the /3-lactone ring in the total synthesis of (-)-panclicin D <1997T16471>. Noyori asymmetric hydrogenation was a key step in a total synthesis of panclicins A-E and was used to establish the stereocenter in aldehyde 140, which in turn directed the stereochemistry of subsequent reactions <1998J(P1)1373>. The /3-lactone ring was then formed by a [2+2] cycloaddition reaction of 140 with alkyl(trimethylsilyl)ketenes and a Lewis acid catalyst. 

Additions of hydride donors to oc-chiral carbonyl compounds that bear only hydrocarbon groups or hydrogen at C-oc typically take place with the diastereoselectivities of Figure 10.14. One of the resulting diastereomers and the relative configuration of its stereocenters are referred to as the Cram product. The other diastereomer that results and its stereochemistry are referred to with the term anti-Cram product. 

It is remarkable and impressive to find that stereochemistry in the conjugate addition of a radical species to an activated olefin is controlled by the chiral bisox-azoline ligand 98 to give a conjugate addition product 100 from 99 in quite high ee and diastereoselectivity (Scheme 12) [58]. Radical trapping by hydrogen abstraction was also shown to be possible in the reaction of 99 to 103, which was controlled by the combination of a chiral alcohol 101 and achiral oxazolidinone 102 [59]. 

An inspection of the stereochemistry at C-2 for the iminosugars revealed that the reductive amination with Pd/C was highly diastereoselective. Interestingly, as already stated [15, 18, 20, 34], we found that the hydrogen was added to the face opposite to the C-4 hydroxyl group, regardless of the relative stereochemistry of the other substituents. Hence, the stereochemistry observed at C-2 was controlled exclusively by the configuration at C-4. An exception was found for the reductive amination of compound 7. In this case, there was no face selectivity and a circa 1 1 diastereomeric mixture was obtained. 

Improved reactivity is offered by 3-hydroxy-A -(4-methylphenylsulfonyl)-4-pentenamine under different conditions (/V-bromosuccinimide in 1,2-dimethoxyethane/water or iodine and sodium hydrogen carbonate in diethyl ether/water). The reactions proceeded at 0-20 °C to give the corresponding 2-haloalkyl-iV-(4-methylphenylsulfonyl)-3-pyrrolidinols in good yield, high diastereoselectivity was observed in favor of the 2,3-m-isomer (Table 5). In this cyclization even the presence of a phenyl substituent at C-5 does not affect the relative stereochemistry of the C-2 and C-3 substituents92-94. 

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