Photodecarboxylative additions of α-keto carboxylates to phthalimides alkylation, acylation and ring expansion

The influence of the substitution pattern on reactivity and selectivity of the photodecarboxylative addition of α-keto carboxylates to N-methyl phthalimide was investigated. Secondary and tertiary α-keto carboxylates as well as glyoxylate gave alkylation and reduction products 2a-d, respectively. Pyruvate and the α-keto leucine anion both gave the ring expansion products 3e and 3f. In the latter case the acylation product 4e was additionally isolated

Photochemistry of MTM- and MTE-esters of ω-phthalimido carboxylic acids: macrocyclization versus deprotection

The photochemistry of five linear methylthiomethyl (MTM)-esters of ω-phthalimido carboxylic acids Pht=N−(CH₂)nCOOCH₂SCH₃ 1a−e (n = 1, 2 , 3, 5, and 10), of the two methylthioethyl (MTE)-esters Pht=N−(CH₂)nCOOCH₂CH₂SCH₃ 2a,b (n = 1, 2), and of the two methyl-substituted MTM/MTE esters 3a and 3b was investigated. Two reaction channels were observed:  (i) photocyclization to give medium-sized and macrocyclic rings, (ii) photochemical deprotection to give the free carboxylic acids. Photocyclization of 1b and 1c (n = 2, 3) resulted in 4b,c in excellent yields whereas the substrates 1a and 1d,e with shorter as well as longer spacer groups (n = 1, 5, 10) gave preferentially the deprotected products 5a,d,e. Subsequent photolysis afforded N-methylphthalimide (6) from 5a. The MTE-esters 2a and 2b gave the macrocyclic lactones 7 and E-8. Thus, the competition between cyclization and deprotection strongly depended on the chain length of the hydrocarbon linker between phthalimido chromophore and ester group. To examine the influence of the position of the ester group in the linker chain the model substrates 3a and 3b with identical number of atoms separating electron donor and acceptor group were investigated. The more flexible MTE-derivative 3b cyclized to give a 4:1 diastereoisomeric mixture of cis/trans-9b, whereas photolysis of the more reluctant MTM-ester 3a resulted in cis-9a only after prolonged irradiation. These results show that MTM can function as a photolabile protecting group whereas MTE cannot be removed photochemically. The distance dependence of the secondary reaction steps indicates that the primary electron transfer is not necessarily induced starting from close contact geometries

The photodecarboxylative addition of carboxylates to phthalimides: scope and limitations

Intermolecular photoinduced decarboxylative additions of a series of alkylcarboxylates to N-substituted phthalimides gave the corresponding hydroxy-phthalimidines in moderate to high yields of 39-89%. The potassium salt of 1- adamantanecarboxylic acid predominately underwent simple decarboxylation when irradiated in the presence of N-methylphthalimide. In case of phthalimides carrying suitable leaving groups within the N-side chain, decarboxylation, retro-Aldol cleavage or decarbonylation preceded the intermolecular addition step

Photodecarboxylative benzylations of phthalimides

Photoadditions of phenylacetates to phthalimides give the corresponding benzylated hydroxyphthalimidines in moderate to high yields of 29–90%. With 2-phenylpropanoate, photoaddition affords a diastereoisomeric mixture in a de of 24% in favour of the like-diastereoisomer. L-3-Phenyl lactate and\ud 2-oxo-3-phenylpropanoate both furnish the benzylated product through subsequent loss of formaldehyde and decarbonylation, respectively

Oxygenated germacranes from Santolina chamaecyparissus

The polar fraction of an extract of Santolina chamaecyparissus ssp. squarrosa yielded six new germacrane derivatives and a novel seco-germacrane lactone. The structures have been derived from spectral data, X-ray diffraction and chemical correlations

A photochemical route for efficient cyclopeptide formation with a minimum of protection and activation chemistry

This protocol represents a new route for cyclopeptide formation with a minimum of protection and activation chemistry and is applied for more complex structures in ongoing work. These preliminary results suffer from medium chemical yields due to substantial hydrolysis at high pH, a competing process which can be suppressed using buffered aqueous conditions