Asymmetric Induction in Hydrogen‐Mediated Reductive Aldol Additions to α‐Amino Aldehydes Catalyzed by Rhodium: Selective Formation of syn‐Stereotriads Directed by Intramolecular Hydrogen‐Bonding.

Abstract

Amino alcohols P 0130Asymmetric Induction in Hydrogen-Mediated Reductive Aldol Additions to α-Amino Aldehydes Catalyzed by Rhodium: Selective Formation of syn-Stereotriads Directed by Intramolecular Hydrogen-Bonding. -In the presence of the Rh catalyst, vinyl ketones undergo reductive addition to monoprotected α-amino aldehydes with high levels of syn-aldol selectivity accompanied by high levels of anti--Felkin-Anh control. Intramolecular hydrogen bonding plays a key role in both activating the α-amino aldehyde toward the reaction and directing the facial selectivity.

Formal Total Synthesis of Manzacidin B via Sequential Diastereodivergent Henry Reaction

“…On the other hand, in the transition-state assembly for the reaction of (4S)-5c, the formyl group might interact with the NH group via intramolecular hydrogen bonding (bottom Scheme). 17 The trityloxymethyl group would shield the front side of the formyl group, and the nitronate was considered to approach the Si face of the formyl group (from the back side) to give the desired (4S,5R)-6c as a major product. The reason why the use of tetrabutylammonium and phosphonium salts improved the diastereoselectivity was considered to be the fact that these aprotic and sterically hindered countercations did not disrupt the formation of the intramolecular hydrogen bonding.…”

Intramolecular Hydrogen-Bond Activation: Strategies, Benefits, and Influence in Catalysis

“…Regarding asymmetric processes, Krische found that the use of N-Boc-α-aminoaldehydes was the key for the stereocontrolled reductive aldol reaction of vinyl ketones to α-chiral aldehydes (Scheme 6, bottom). 25 The presence of an intramolecular hydrogen bond between CHO•••HNBoc was a determinant for the transformation in terms of reactivity (excellent yields) and stereoselectivity (>20:1 value) of the final compounds. The importance of this interaction was demonstrated when the NH moiety was methylated and lower values for the aldol adducts (66 versus 17% yield; 20:1 versus 7:1 dr) were achieved.…”