Synthesis of P,N-heterocycles from omega-amino-H-phosphinates: conformationally restricted alpha-amino acid analogs.

P,N-heterocycles (3-hydroxy-1,3-azaphospholane and 3-hydroxy-1,3-azaphosphorinane-3-oxide) are synthesized in moderate yield from readily available omega-amino-H-phosphinates and aldehydes or ketones via an intramolecular Kabachnik-Fields reaction. The products are conformationally restricted phosphinic analogs of alpha-amino acids. The multigram-scale syntheses of the H2N(CH2)(n)PO2H2 phosphinic precursors (n = 1, 2, 3) and some derivatives are also described.

MALDI-TOF MS analysis of soluble PEG based multi-step synthetic reaction mixtures with automated detection of reaction failure.

Macromolecules of tunable solubility, used to mimic inert insoluble materials while maintaining solution conditions, allowed the performance of efficient supported organic chemistry and facilitated in situ reaction monitoring. To satisfy the high throughput requirements of automated synthetic processes, organic syntheses carried out on bifunctional polyethylene glycol polymers (PEG(3400)-OH) were monitored step-by-step by matrix assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS). A protocol was designed to control the ionization mechanism of such polymers exhibiting high affinity for alkali metal cations. Automated, rapid, and reliable data interpretation was performed by an in-house developed visual basic application relying on the sodiated ion accurate monoisotopic mass measurement. The methodology was illustrated through the monitoring of a six-step synthetic scheme.

NiCl2-catalyzed hydrophosphinylation.

[reaction: see text] A new nickel-based catalytic system has been developed for phosphorus-carbon bond formation. The addition of alkyl phosphinates to alkynes is catalyzed by nickel chloride in the absence of added ligand. The reaction generally proceeds in high yields, even with internal alkynes, which were poor substrates in our previously reported palladium-catalyzed hydrophosphinylation of alkyl phosphinates. The method is useful for the preparation of H-phosphinate esters and their derivatives. The one-pot synthesis of various important organophosphorus compounds is also demonstrated. The reaction can be conducted with microwave heating.

Sequential aza-Baylis-Hillman/ring closing metathesis/aromatization as a novel route for the synthesis of substituted pyrroles.

A new route to diverse 2-substituted-3-methoxycarbonyl pyrroles has been developed. Diverse SES protected alpha-methylene beta-aminoesters were obtained by a 3-component aza-Baylis-Hillman reaction. Diversity arose from the aryl aldehydes which can be used in this reaction. N-Alkylation with allyl bromide under mild conditions provided the corresponding dienes. These substituted dienes were cyclized by ring closing metathesis at room temperature or under microwave-activation with Grubbs-type II catalyst to yield SES-protected pyrroline intermediates. The final pyrroles were obtained by base-promoted dehydrodesulfinylation/aromatization. The scope of each of these reactions was explored.