Asymmetric Intramolecular [2 + 2] Photocycloadditions:  α- and β-Hydroxy Acids as Chiral Tether Groups

Abstract

Chiral alpha- and beta-hydroxy acids such as (S)-lactic acid, (S)-phenyllactic acid, (S)-mandelic acid, or (3R)-3-hydroxybutyric acid have been used as tether groups for intramolecular and diastereoselective [2 + 2] photocycloaddition of 3-oxocyclohexene carboxylic acid derivatives. Total regiocontrol toward the straight adduct and high diastereoselectivities (up to 94%) were observed in the case of butenyl lactate 11. After separation of the two diastereoisomers, cleavage of the chiral tether under basic conditions afforded cyclobutane lactones in good yield and enantiomeric pure form. An X-ray structure has been recorded that confirmed the relative and absolute configuration of the three contiguous stereogenic centers assigned according to CD spectra.

Photochemistry of Cyclobutanes: Synthesis and Reactivity

“…The derivatives (331a-c) all undergo the intramolecular addition with the formation of the products shown in Scheme 10. The cycloadditions are diastereoselective, as can be seen from the de values reported 210 . The same authors have reported earlier on these additions 211 -213 .…”

Recent Advances in the Synthesis of Cyclobutanes by Olefin [2 + 2] Photocycloaddition Reactions

“…Piva and co-workers have studied the influence of various tethers on the course of intramolecular [2 + 2] photocycloaddition reactions. 386 − 388 A lactic acid-based tether induced a high facial diastereoselectivity in the reaction of enone ester 199 ( Scheme 62 ). The major product 200 clearly prevailed over the minor diastereoisomer 201 .…”

Analogs of N′-hydroxy-N-(4H,5H-naphtho[1,2-d]thiazol-2-yl)methanimidamide inhibit Mycobacterium tuberculosis methionine aminopeptidases

“…7-Methoxy-4H,5H-naphtho[1,2- d ]thiazol-2-amine (85 mg, 365 µmol) was coupled with ( S )- O -( tert -butyldiphenylsilyl)lactic acid 31 using HBTU (152 mg, 1.1 equiv.) and i -Pr 2 NEt (230 µL, 3.5 equiv.)…”