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Esta tesis describe el estudio de la aplicación en síntesis de N-terc-butanosulfinil derivados de alquil, alquenil, homoalil y homopropargil aminas como intermedios para acceder a moléculas orgánicas de mayor complejidad. Por un lado, se ha estudiado la adición de compuestos organomagnesianos y organolíticos a N-terc-butanosulfinil iminas, y los distintos derivados de aminas que se obtienen como resultado se han usado como precursores de alcaloides pirrolodínicos y piperidínicos, así como para acceder a anillos tipo azepano. Por otro lado, también se presentan aplicaciones en síntesis de N-terc-butanosulfinil homoalil y homopropargil aminas, que pueden participar en reacciones de oxidación allílica y cicloadiciones [2+2+2], respectivamente, para dar lugar a compuestos polifuncionalizados, en el caso de los derivados de homoalil aminas, y derivados de 9-amino-9, 10-dihidrofenantrenos y 1,2,3,4-tetrahidroisoquinolinas, en el cado de los derivados de homopropargil aminas.

The synthesis of nitrogen-containing heterocycles, including natural alkaloids and other compounds presenting different types of biological activities have proved to be successful employing chiral sulfinyl imines derived from tert-butanesulfinamide. These imines are versatile chiral auxiliaries and have been extensively used as eletrophiles in a wide range of reactions. The electron-withdrawing sulfinyl group facilitates the nucleophilic addition of organometallic compounds to the iminic carbon with high diastereoisomeric excess and the free amines obtained after an easy removal of the tert-butanesulfinyl group can be transformed into enantioenriched nitrogen-containing heterocycles. The goal of this review is to the highlight enantioselective syntheses of heterocycles involving the use of chiral N-tert-butanesulfinyl imines as reaction intermediates, including the synthesis of several natural products. The synthesis of nitrogen-containing heterocycles in which the nitrogen atom is not provided by the chiral imine will not be considered in this review. The sections are organized according to the size of the heterocycles. The present work will comprehensively cover the most pertinent contributions to this research area from 2012 to 2020. We regret in advance that some contributions are excluded in order to maintain a concise format.

The synthesis of nitrogen-containing heterocycles, including natural alkaloids and other compounds presenting different types of biological activities have proved to be successful employing chiral sulfinyl imines derived from tert-butanesulfinamide. These imines are versatile chiral auxiliaries and have been extensively used as eletrophiles in a wide range of reactions. The electron-withdrawing sulfinyl group facilitates the nucleophilic addition of organometallic compounds to the iminic carbon with high diastereoisomeric excess and the free amines obtained after an easy removal of the tert-butanesulfinyl group can be transformed into enantioenriched nitrogen-containing heterocycles. The goal of this review is to the highlight enantioselective syntheses of heterocycles involving the use of chiral N-tert-butanesulfinyl imines as reaction intermediates, including the synthesis of several natural products. The synthesis of nitrogen-containing heterocycles in which the nitrogen atom is not provided by the chiral imine will not be considered in this review. The sections are organized according to the size of the heterocycles. The present work will comprehensively cover the most pertinent contributions to this research area from 2012 to 2020. We regret in advance that some contributions are excluded in order to maintain a concise format.

The reaction of N-tert-butanesulfinyl imines 1 with 1,3-dibromopropene (2), in the presence of indium metal, in saturated aqueous solution of sodium bromide, produced bromohomoallylamine derivatives 3 with total facial diastereoselectivity for the imine addition, and moderate yields. These compounds were easily transformed into the corresponding vinyl aziridines 5 upon deprotonation with KHMDS in THF, the intramolecular cyclization taking place in a stereospecific manner in moderate to high yields.

The addition of but-3-enylmagnesium bromide and pent-4-enylmagnesium bromide to N-tert-butanesulfinyl aldimines in toluene as solvent proceeds with high diastereoselectivity to yield the corresponding products of homoallylation and bis-homoallylation, respectively. The reactions are diastereoselective, and the configuration of the sulfur atom of the sulfinyl group determined the stereochemical outcome. The reaction products are aminoalkene derivatives of potential synthetic interest as precursors of nitrogen containing heterocycles.

The reaction of N-tert-butanesulfinyl imines 1 with 1,3-dibromopropene (2), in the presence of indium metal, in saturated aqueous solution of sodium bromide, produced bromohomoallylamine derivatives 3 with total facial diastereoselectivity for the imine addition, and moderate yields. These compounds were easily transformed into the corresponding vinyl aziridines 5 upon deprotonation with KHMDS in THF, the intramolecular cyclization taking place in a stereospecific manner in moderate to high yields.

The addition of but-3-enylmagnesium bromide and pent-4-enylmagnesium bromide to N-tert-butanesulfinyl aldimines in toluene as solvent proceeds with high diastereoselectivity to yield the corresponding products of homoallylation and bis-homoallylation, respectively. The reactions are diastereoselective, and the configuration of the sulfur atom of the sulfinyl group determined the stereochemical outcome. The reaction products are aminoalkene derivatives of potential synthetic interest as precursors of nitrogen containing heterocycles.

The palladium(II)-catalyzed oxidation of homoallylic amine derivatives resulting from the allylation of N-tert-butanesulfinyl imines with allyl bromide led to the formation of the corresponding terminal allylic acetates in a regioselective fashion in moderate yields. In the case of the homoallylic amine derivatives obtained using cyclohexenyl bromide as the allylating reagent, the allylic oxidation took place with high regio- and diastereoselectivity and yields ranging from 40 to 85%.

The palladium(II)-catalyzed oxidation of homoallylic amine derivatives resulting from the allylation of N-tert-butanesulfinyl imines with allyl bromide led to the formation of the corresponding terminal allylic acetates in a regioselective fashion in moderate yields. In the case of the homoallylic amine derivatives obtained using cyclohexenyl bromide as the allylating reagent, the allylic oxidation took place with high regio- and diastereoselectivity and yields ranging from 40 to 85%.

The palladium-catalyzed allylation of N-tert-butanesulfinyl imines with allylic alcohols in the presence of InI as reducing reagent takes place with high diastereoselectivity in reasonable yields. The reaction with crotyl alcohol is totally regioselective, leading to the anti-diastereomer as the main reaction product.

The palladium-catalyzed allylation of N-tert-butanesulfinyl imines with allylic alcohols in the presence of InI as reducing reagent takes place with high diastereoselectivity in reasonable yields. The reaction with crotyl alcohol is totally regioselective, leading to the anti-diastereomer as the main reaction product.