Suresh Pindi

Asymmetric catalytic aza-Morita–Baylis–Hillman reaction for the synthesis of 3-substituted-3-aminooxindoles with chiral quaternary carbon centers

The asymmetric catalytic aza-Morita-Baylis-Hillman (aza-MBH) reaction of isatin-derived ketimines with MVK has been established by using chiral amino and phosphino catalysts. The reaction resulted in biomedically important 3-substituted 3-amino-2-oxindoles in good yields (>80% for most cases) and with excellent enantioselectivity (90-99% ee). Twenty-eight cases assembled with chiral quaternary stereogenic centers have been examined under convenient systems.

Asymmetric catalytic Strecker reaction of N-phosphonyl imines with Et2AlCN using amino alcohols and BINOLs as catalysts

The asymmetric catalytic Strecker reaction of achiral N-phosphonyl imines with Et(2)AlCN has been established. Both free amino alcohols and BINOLs have been proven to be effective catalysts to afford excellent enantioselectivities and yields. The N-phosphonyl group can be readily cleaved under mild conditions and enable purification of crude products by simple washing with hexane. The cleaved N,N-dialkyl diamine auxiliary can be recovered quantitatively via n-BuOH extraction. The scope for both N-phosphonyl imines and catalysts was vastly studied for this new catalytic system.

Efficient Domino Approaches to Multifunctionalized Fused Pyrroles and Dibenzo[b,e][1,4]diazepin-1-ones

Efficient domino approaches for the synthesis of multifunctionalized tricyclic fused pyrroles and dibenzo[b,e][1,4]diazepin-1-ones have been established. The reaction pathways were controlled by varying enaminones with different substituted patterns to give a series of new fused pyrroles and dibenzo[b,e][1,4]diazepin-1-ones selectively. The complete anti diastereoselectivity was achieved for the first reaction.

N‐Phosphinyl Imine Chemistry (I): Design and Synthesis of Novel N‐Phosphinyl Imines and their Application to Asymmetric aza‐Henry Reaction

Novel chiral N‐phosphinamide and N‐phosphinyl imines have been designed, synthesized and applied to asymmetric aza‐Henry reaction to give excellent chemical yields (92%– quant.) and diastereoselectivity (91% to >99%de). The reaction showed a great substrate scope in which aromatic/aliphatic aldehyde‐ and ketone‐derived N‐phosphinyl imines can be employed as electrophiles. The chiral N‐phosphinamide can be stored at room temperature for more than 2 months without inert gas protection, and chiral N‐phosphinyl imines were also proven to be highly stable at room temperature for a long period under inert gas protection. The N‐phosphinyl group enabled the product purification to be performed simply by washing crude product with EtOAc and hexane. This reaction joined other eight GAP (Group‐Assistant‐Purification) chemistry processes that were developed in our laboratories. The absolute configuration has been unambiguously determined by converting a β‐nitroamine product into a known N‐Boc sample.

Asymmetric synthesis of α-amino-1,3-dithianes via chiral N-phosphonyl imine-based Umpolung reaction without using chromatography and recrystallization.

A series of α-amino-1,3-dithianes have been synthesized via the asymmetric Umpolung reaction of 2-lithio-1,3-dithianes with chiral N-phosphonyl imines in good chemical yields (up to 82%) and good to excellent diastereoselectivities (>99:1). The manner by which chiral N-phosphonyl imines are slowly added into the solution of 2-lithio-1,3-dithiane was found to be crucial for achieving excellent diastereoselectivity. The current synthesis was proven to follow the GAP chemistry (group-assistant-purification chemistry) process, which avoids traditional purification techniques of chromatography or recrystallization, i.e., the pure chiral α-amino-1,3-dithianes attached with the chiral N-phosphonyl group were readily obtained by washing the solid crude products with hexane or a mixture of hexane-ethyl acetate.

Design, Synthesis, and Applications of Chiral N-2-Phenyl-2-propyl Sulfinyl Imines for Group-Assisted Purification (GAP) Asymmetric Synthesis

A new chiral (Rs)-2-phenyl-2-propyl sulfinamide has been designed and synthesized; its derived aldimines and ketimines have been applied for asymmetric addition reaction with allylmagnesium bromide. The reaction was conveniently performed at room temperature to give a series of homoallylic amines in high yields (up to quant) and diastereoselectivity (up to >99% de). The pure products were obtained by relying on group-assisted purification (GAP) chemistry to avoid traditional purification methods of column chromatography or recrystallization. The conversion of disulfide to (R(s))-thiosulfinate which contains a newly generated polar group was also confirmed to be of the GAP chemistry in which washing crude product can generate pure enantiomer. The absolute stereochemistry has been determined by X-ray analysis.

The GAP chemistry for chiral N-phosphonyl imine-based Strecker reaction

Chiral N-phosphonyl imines were found to be efficient electrophiles for reaction with diethylaluminium cyanide, a non-volatile and inexpensive cyanide source. The reaction produced chiral Strecker adducts, α-aminonitriles, in excellent chemical yields (94–98%) and diastereoselectivities (95 : 5 to >99%). This synthesis was confirmed to follow the GAP chemistry (group-assistant-purification chemistry) process, which can avoid traditional chromatography and recrystallization purifications, i.e., the pure chiral α-aminonitriles bearing a chiral N-phosphonyl group can be simply obtained by washing the solid crude products with hexane. The chiral N-phosphonyl auxiliary can be easily cleaved under mildly acidic conditions and quantitatively recycled by a one-time extraction with n-butanol.

Asymmetric Carbamoyl Anion Additions to Chiral N-Phosphonyl Imines via the GAP Chemistry Process and Stereoselectivity Enrichments.

Carbamoyl anions were found to smoothly react with chiral N-phosphonyl imines in toluene at −78 °C to r.t. using LiHMDS as the base. Group-assisted purification (GAP) has been utilized to give the pure amides without using column chromatography or recrystallization. The asymmetric reaction resulted in chiral N-phosphonyl amino amides with good to excellent yields (71–99%) and good crude diastereoselectivities (dr 84:16–95:5). In this GAP procedure, the crude solids are washed with diethyl ether to afford the pure products, as revealed by 1H NMR analysis; GAP washing consistently increases the diastereopurity of the products, resulting in excellent diastereoselectivities, often with final dr > 99:1. Interestingly, the diastereoenriched products can be obtained either in the ether solution or as the suspended solid, depending on the substrate.