Catalytic Allylation of Hypophosphorous Acid and H‐Phosphinic Acids with Primary Allylic Amines

Abstract

Primary allylic amines serve as suitable allylic electrophiles for the allylation reactions of hypophos-A C H T U N G T R E N N U N G phorous acid and H-phosphinic acids. In the presence of tris(dibenzylideneacetone)dipalladium(0) ([Pd 2 A C H T U N G T R E N N U N G (dba) 3 ], 0.1 mol %) and Xantphos (0.2 mol %), aqueous hypophosphorous acid was allylated by a-unbranched primary allylic amines in a highly regioselective fashion to give structurally diverse allylic H-phosphinic acids in good to excellent yields with exclusive E selectivity. Moreover, increasing the catalyst loading to 1 mol % and adding aqueous phosphoric acid (1.2 equiv.) permitted the allylation of H-phosphinic acids with a-unbranched primary allylic amines to proceed to give disubstituted phosphinic acids in good to excellent yields.Allylic halides and alcohol derivatives frequently serve as electrophilic components in the Tsuji-Trost reaction, which is powerful for the synthesis of unsaturated compounds. [1] While allylic amines have rarely been used directly as allylic electrophiles because of the poor leaving ability of amino groups, [2] it would be rewarding to develop the Tsuji-Trost reaction with allylic amines to explore new reactivity and selectivity. It is noteworthy that, in general, the synthetic routes to allylic amines are not longer than those to allylic halides and alcohol derivatives. Allylic amines can be prepared by reduction of a,b-unsaturated amides or nitriles by reductive amination of a,b-unsaturated carbonyl compounds or by modification of allylamines through the Heck reaction.[3] Moreover, the basicity of allylic amines permits their purification in large quantities by simple extractive procedures instead of routine chromatography. Sporadic studies have shown that allylic amines, in most cases secondary and tertiary ones, can undergo the Tsuji-Trost reaction with a few types of carbon, [3b-d, 4] nitrogen, [5] and sulfur nucleophiles. [3a,e, 6, 7] To the best of our knowledge, there is no previous report on the Tsuji-Trost reaction of allylic amines with phosphorus nucleophiles. Herein, we report efficient allylation reactions of hypophosphorous acid and Hphosphinic acids with primary allylic amines, which are more atom-economic relative to those with commonly used allylic electrophiles because ammonia is the sole byproduct.The Tsuji-Trost reaction has been successfully extended to the allylation of a few phosphorus nucleophiles for the synthesis of allylic-(H)-phosphinic acids and their derivatives.[8] Montchamp and co-workers reported that hypophosphorous acid, hypophosphite salts, [9] and H-phosphinic acids [10] could undergo palladium-catalyzed allylation with allylic alcohols, esters, and carbonates.[11] When allylic alcohols were used as the allylic electrophiles, they underwent Fischer-like esterification prior to palladium-catalyzed C À O bond cleavage. Inspired by these reports, together with our interest in exploring new reactions through CA C H T U N G T R E N N U N G (sp 3 ) À N bond cleavage...

Transition-Metal-Catalyzed Cleavage of C–N Single Bonds

“…Primary allylic amines are a class of important alternatives of allylic halides and alcohol derivatives to deliver allyl units in the Tsuji–Trost reaction because of the higher atom economy and easy preparation on a large scale. ,− Tian et al developed the Pd-catalyzed coupling reactions of primary allylic amines with various nucleophiles via the cleavage of the C–N bond to prepare multiple allylic derivatives, 7 – 9 , in good to excellent yields with exclusive selectivity (Scheme ). − These nucleophiles include sulfonate salts, boronic acids, boronates, and ketone-stabilized phosphonium ylides. In these reactions, the NH 2 group is activated by B­(OH) 3 , and serves as a leaving group to generate allylic electrophiles. − Then π-allyl–Pd intermediate 10 is produced via oxidative addition of Pd species to the C–N bond.…”

Catalytic C–N and C–H Bond Activation: ortho-Allylation of Benzoic Acids with Allyl Amines

“…In 2002, Hartwig et al reported a nickel-catalyzed amine exchange reaction through oxidative cleavage of C–N bonds . The groups of Yudin, Zhang, Aggarwal, and Tian et al independently achieved allyl substitutions of allyl amines with the use of various strong nucleophiles, such as amines, carbonyl compounds, sulfinate salts, phosphonium ylides, and phosphinic acids, via η 3 -allyl–metal intermediates (Scheme a).…”

Recent Methodologies That Exploit Oxidative Addition of C–N Bonds to Transition Metals

“…For chiral allylamines 234 , the reaction proceeded with inversion (100% es ) and benefited from the addition of TMEDA as a ligand, whereas the additive B­(OH) 3 had a detrimental effect. Since Trost’s initial observation, there have been numerous reports of Tsuji–Trost-type allylations whereby the electrophilic component is a (Brønsted or Lewis acid activated) allylamine, primarily under Pd(0) catalysis, with a variety of nucleophiles, including those based on carbon, nitrogen (intramolecular), phosphorus, and sulfur …”

“…For chiral allylamines 234, the reaction proceeded with inversion (100% es) and benefited from the addition of TMEDA as a ligand, whereas the additive B(OH) 3 had a detrimental effect. Since Trost's initial observation, there have been numerous reports of Tsuji− Trost-type allylations whereby the electrophilic component is a (Brønsted or Lewis acid activated) allylamine, primarily under Pd(0) catalysis, with a variety of nucleophiles, including those based on carbon, 144 nitrogen (intramolecular), 145 phosphorus, 146 and sulfur. 147 Important advances toward catalytic enantio-and regioselective allylations starting from allylamines have emerged, including a selected example of enantioselective α-allylation of branched aldehydes by List (Scheme 27A) 148 and a recent example of enantioselective α-allylation of β-keto esters reported by Tian (Scheme 27B).…”