Synthesis of β-Amino-Functionalized α-exo-Methylene-γ-butyrolactones via a β-Lactam Synthon Strategy

Abstract

A convenient and effective synthetic approach was developed to access a structurally novel class of β-amino-functionalized α-exo-methylene-γ-butyrolactones using chiral β-lactam synthons.

α-methylene carbonyl compounds - Michael acceptor - β-lactam synthon - α-exo-methylene-β-lactam - β-amino-α-exo-­methylene-γ-butyrolactone

References

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The compound 7 was obtained as a 1:1 mixture of inseparable diastereomers. ^¹H NMR data for 7: δ = 3.93 (m, 1 H, CH), 3.70 (m, 1 H, CH), 3.68-3.56 (m, 3 H, CH₂, CH, and CH₂), 3.45 (dt, J = 7.8, 13.8 Hz, 1 H, CH₂), 3.33 (s, 3 H, OCH₃), 2.79 (m, 1 H, CH ₂NH), 1.57-1.28 (m, 18 H, CH₂), 0.90-0.86 (m, 6 H, CH₃), 0.88, 0.87 (s, 9 H, t-C₄H₉), 0.08, 0.06 (s, 3 H, CH₃), 0.04, 0.00 (s, 3 H, CH₃).

<A NAME="RF09010SS-13">13</A>

It should be noted that our initial attempts to generate the target compounds via cyclization of γ-hydroxy esters under basic and/or mild acidic conditions failed due to low stability of the products.

<A NAME="RF09010SS-14">14</A>

The formation of cis-8e and cis-8f may be interpreted in terms of intramolecular nucleophilic attack of alkoxides, generated in situ from removal of the TBS groups, which would act as the primary reactive species.

For other synthetic examples, see:

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