Aminoalkyl-Substituted α-Methylene-γ-butyrolactones from α-Amino Acids Using an Indium-Mediated Barbier Allyl Addition

Abstract

The indium‐mediated reaction of Z‐protected α‐amino aldehydes 1–6 with 2‐(bromomethyl)acrylates 8/9 in aqueous solvents has been investigated. The preference for the formation of syn‐configured homoallyl alcohols 10–16 (diastereoselectivities ranging from 2:1 to 32:1, yields 68–93%) may be explained by a chelate‐controlled reaction. No racemization occurred during the preparation and transformation of the amino aldehydes. Acid‐catalyzed esterification (H2SO4 in Et2O) led to α‐methylene‐γ‐butyrolactones 17–22 with yields ranging from 89 to 97%. The configurations of all diastereoisomers were established by five X‐ray crystallographic analyses and by comparision of the NMR spectra.

Reversible Substrate Anchoring: NC‐SPOS as a Sustainable Approach to Solid‐Supported Organic Synthesis

“…In contrast, in the case of In‐mediated reactions good yields were obtained, but inorganic precipitates hampered filtration and matrix purification for reuse. However, the homogenous reagents generated from SnCl 2 /KI19 with allyl bromide, ethyl 2‐bromomethylacrylate,20 and even propargyl bromide consistently gave high yields of isolated adducts 3 – 5 .…”

Reversible Substrate Anchoring: NC‐SPOS as a Sustainable Approach to Solid‐Supported Organic Synthesis

“…Chemie bromide, ethyl 2-bromomethylacrylate, [20] and even propargyl bromide consistently gave high yields of isolated adducts 3-5.…”

Indium in Organic Synthesis

“…51 Scheme 15 Allyl addition to Reetz-type aldehydes 51 When carbamate-protected amino aldehydes were reacted with indium and allyl bromide or methyl 2-(bromomethyl)acrylate, respectively, a chelate-controlled reaction led to a preferred formation of the syn-product. [63][64][65] Selectivities were somewhat higher for the products obtained from methyl 2-(bromomethyl)acrylate. 63,64 These have further been used in the synthesis of γ-aminoalkyl-substituted αmethylene γ-butyrolactones.…”

“…[63][64][65] Selectivities were somewhat higher for the products obtained from methyl 2-(bromomethyl)acrylate. 63,64 These have further been used in the synthesis of γ-aminoalkyl-substituted αmethylene γ-butyrolactones. 64,65,67 When the carbamate protection was replaced by a phthaloyl protection, the anti-product was formed predominantly, suggesting that no chelation was present in the transition state (…”

“…α-Amino aldehydes are -like carbohydrates -an easily accessible class of compounds which have been fruitfully used in indium-mediated allyl additions. 51,[63][64][65][66] The selectivities with N,N-dibenzyl-substituted α-amino aldehydes (Reetz-type aldehydes) are clearly ruled by steric effects. The preferred formation of anti-products showed that internal chelating was not operative (Scheme 15).…”