Refernces
10.1021/jo00347a060
The research focuses on the novel p' metalations of α,β-unsaturated tertiary amides and their subsequent reactions with various electrophiles, which is a new approach to p' substitution of α,β-unsaturated carboxylic acid derivatives. The purpose of this study was to explore the potential of diisopropyl tertiary amides to undergo p' metalation at low temperatures, leading to stable lithio-α,β-unsaturated amides that can react with a variety of electrophiles, including cases where five-membered rings are formed. The conclusions drawn from the research indicate that this method is effective for achieving substitution at the p' position and has significant synthetic potential, as demonstrated by the successful preparation of the p'-lithiomethacrylate synthon and the control of syntheses with α,β-unsaturated carboxylic acid derivatives. The chemicals used in the process include sec-butyllithium, N,N-diisopropyl-1-cyclohexenecarboxamide, and a range of electrophiles such as deuterium oxide, alkyl halides, ketones, and N,N-dimethylbenzamide, among others.
10.1002/anie.201700195
The study reports a Pd-catalyzed asymmetric reductive Heck reaction using diboron–water as a hydride source. The researchers used N-aryl acrylamides as substrates and Pd(OAc)2 as the catalyst, along with tBuPhOX as the ligand and tetrahydroxydiboron as the diboron reagent. The reaction proceeds via intramolecular asymmetric carbopalladation of the substrates, followed by reduction of the C(sp3)-Pd intermediate using water as the hydride source, yielding enantioenriched 3,3-disubstituted oxindoles with high yields and enantioselectivities. The ligand plays a crucial role in determining both the enantioselectivity and the reaction pathways, allowing for either hydroarylation (reductive Heck) or carboborylation products. The study also demonstrates the synthesis of deuterated compounds by using heavy water (D2O) as a deuterium donor in combination with bis(catecholato)diboron.
10.1016/S0040-4039(00)81514-2
The research focuses on the synthesis of specifically deuterated 1,3-diethoxy-carbonylallylidene-triphenylphosphonium ylides. The purpose was to develop methods for introducing deuterium labels in the ?- and ?-positions of the allylidene-phosphonium ylide without deuterium scrambling. In the research, ethyl propynoate serves as a key starting material for the synthesis of deuterated compounds. It is used in the Michael addition reaction to produce the ?-deuterated phosphonium ylide and also as a reactant in the synthesis of ethyl 3-deuteriopropynoate, which is crucial for the ?-deuteration process. Deuterium oxide (D2O) plays a vital role in the deuterium exchange reactions. It is used to introduce deuterium atoms into the molecules, specifically in the synthesis of ethyl 3-deuteriopropynoate and in the acid-catalyzed deuterium exchange to produce the ?-deuterated phosphonium ylide. Sodium deuteroxide (NaOD) acts as a base in the deuterium exchange process. It is used to facilitate the deuterium exchange reactions and to neutralize any acid present, ensuring that the deuterium atoms are retained in the final products. Tetrabutylammonium iodide (TBAI) functions as a phase-transfer catalyst. It helps to transfer reactants between the organic and aqueous phases, enhancing the efficiency of the deuterium exchange reactions in the synthesis of ethyl 3-deuteriopropynoate. For ?-deuteration, ethyl propynoate was treated with deuterium oxide under phase transfer conditions to synthesize ethyl 3-deuteriopropynoate, which was then reacted with the ylide to produce the ?-deuterated phosphonium ylide. For ?-deuteration, the ylide was subjected to acid-catalyzed, regiospecific deuterium exchange with deuterium oxide and deuterium chloride, followed by base treatment to avoid deuterium loss. The methods resulted in high deuterium incorporation (>90%) and good yields (66-80%), providing a reliable way to introduce deuterium labels for further studies.
