The Baylis-Hillman Reaction with Chiral α-Amino Aldehydes under Racemization-Free Conditions

Abstract

The Baylis-Hillman reaction with chiral a-amino aldehydes has been revisited. The reaction carried out under the influence of ultrasound avoids the aldehyde racemization almost completely, providing useful chiral substrates which can be used as starting materials for the synthesis of natural products. To demonstrate the synthetic applicability of these adducts, the easy preparation of a bicyclic lactam with an indolizidinic skeleton was accomplished.

Green Asymmetric Organocatalysis

“…A set of chiral α‐amino aldehydes 95 reacted with methyl acrylate ( 96 ) in the presence of 1,4‐diazabicyclo[2.2.2]octane (DABCO) under ultrasound irradiation at room temperature (Scheme ) . Products 97 were obtained in yields of up to 86 % and 7:1 anti / syn ratio.…”

A Stereospecific Synthesis and Unambiguous Assignment of the Absolute Configuration of (−)‐erythro‐Mefloquine Hydrochloride

“…Thus, according to literature methods, ( S )‐(−)‐ 2 was converted to methyl ( S )‐(−)‐1‐Boc‐2‐piperidinecarboxylate ( S )‐(−)‐ 3 , [ 17] [α]${{{20\hfill \atop {\rm D}\hfill}}}$ : −55.6 ( c= 0.7, CHCl 3 ); {lit. for 85% ee : [α]${{{20\hfill \atop {\rm D}\hfill}}}$ : −48.1 ( c= 1.11, CHCl 3 )18a and 76% ee : [α]${{{20\hfill \atop {\rm D}\hfill}}}$ : −31.7 ( c= 1.0, CHCl 3 )18b} followed by reduction with Dibal‐H at −78 °C to give ( S )‐(−)‐1‐Boc‐2‐piperidinecarboxaldehyde ( S )‐(−)‐ 4 19 in 76% yield; [α]${{{20\hfill \atop {\rm D}\hfill}}}$ : −77.6 ( c= 1.5, CHCl 3 ); {lit. [α]${{{25\hfill \atop {\rm D}\hfill}}}$ : −77.8 ( c= 1.21, CHCl 3 );20a [α]${{{20\hfill \atop {\rm D}\hfill}}}$ : −77.9 ( c= 1.49, CHCl 3 );20b [α]${{{20\hfill \atop {\rm D}\hfill}}}$ : −77.4 ( c= 1.49, CHCl 3 ) 20c…”

Total Synthesis of Biologically Active Natural Products Based on Highly Selective Synthetic Methodologies

“…Interestingly, L-and D-prolinals showed the opposite match-mismatch relationship to that observed for the acyclic substrates: D-prolinal rather than L-prolinal matched well with β-ICD, resulting in excellent anti-selectivity and good yield. Since the major problems associated with the MBH reaction of a chiral α-amino aldehyde are the racemization of the substrate and difficulty in securing high diastereoselectivity, 12,13) our β-ICD-HFIPA method exhibits a marked advantage in this reaction.…”