Effect of Linker Length on Selectivity and Cooperative Reactivity in Platinum-Catalyzed Asymmetric Alkylation of Bis(phenylphosphino)alkanes

Abstract

The selectivity of catalytic asymmetric transformations of bifunctional symmetrical substrates often depends on the linker between the two reactive sites. If the catalyst controls the selectivity of reactions at both sites, the rac product will be formed in high enantiomeric ratio (er) via asymmetric amplification. Substrate control may augment this selectivity (positive cooperativity) or detract from it (negative cooperativity). Here, we investigated the effect of linker length on the selectivity of catalytic asymmetric alkylation of the bis­(secondary phosphines) PhHP­(CH2) n PHPh (n = 2–6; 1a–e) with benzyl bromide using the base NaOSiMe3 and the catalyst precursor Pt­((R,R)-Me-DuPhos)­(Ph)­(Cl). These reactions yielded the diastereomerically and enantiomerically enriched bis­(tertiary phosphines) Ph­(PhCH2)­P­(CH2) n P­(CH2Ph)­Ph (n = 2–6, 2a–e). Pt-catalyzed benzylation of the model phosphines PH­(Ph)­((CH2) n H) (n = 2–6; 4a–e) gave enantiomerically enriched P­(CH2Ph)­(Ph)­((CH2) n H) (n = 2–6; 5a–e). The partially alkylated bis­(phosphines) PhHP­(CH2) n P­(CH2Ph)­Ph (n = 2, 3, 5; 3a,b,d) were prepared with different degrees of enantiomeric enrichment at the tertiary phosphine centers and then catalytically alkylated to give 2a,b,d. From the diastereoselectivity and enantioselectivity of the transformations 1 → 2 and 3 → 2, the selectivity of each individual alkylation step (1 → 3R or 3S; 3R → 2RR or 2RS; 3S → 2SS or 2SR) could be determined as a function of linker length and compared to the selectivity of alkylation of the model monophosphines 4. The two alkylations of bis­(secondary phosphines) 1b–e with longer linker lengths (n = 3–6) showed identical selectivity, within experimental error. This catalyst control resulted in asymmetric amplification of rac-2. In contrast, the selectivity of the first alkylation of ethano-bridged 1a was lower than that in 1b–e (negative cooperativity), but the selectivity of the second alkylation (of intermediate 3a) increased due to positive cooperativity. Possible mechanistic explanations for the observed dependence of selectivity on linker length are discussed.

Asymmetric Electrophilic Reactions in Phosphorus Chemistry

“…Asymmetric alkylation or arylation of racemic secondary phosphines, catalyzed by chiral Lewis acids, in many cases led to the formation of enantiomerically enriched tertiary phosphines [105][106][107][108][109][110][111][112]. For example, the chiral platinum complex Pt(Me-Duphos)(Ph)(Br) catalyzed the asymmetric alkylation of secondary phosphines with benzyl halides to form tertiary phosphines (or their boranes) in good yields and with 50-93% ee (Equation (77)) [107].…”

“…For example, the chiral platinum complex Pt(Me-Duphos)(Ph)(Br) catalyzed the asymmetric alkylation of secondary phosphines with benzyl halides to form tertiary phosphines (or their boranes) in good yields and with 50-93% ee (Equation (77)) [107]. Secondary phosphines with bulky substituents (Ar') reacted with para-substituted aryl iodides to form tertiary phosphines with an enantiomeric excess up to 88% [105,106]. Glueck [106,107] reported that racemic secondary phosphines in the presence of Pt(Me-Duphos)(Ph)(Br) and NaOSiMe 3 in toluene afforded adducts 4 which interconvert rapidly by P-inversion (S P )-4…”

“…Examples of arylation of secondary phosphines with low enantioselectivity, catalyzed by this complex, are described. Arylation of secondary phosphines with anisyl iodide, catalyzed by the chiral palladium complex (82) Arylation of secondary phosphines by aryl halides, catalyzed by chiral copper complexes [97], platinum [106,110,115,117], ruthenium [108,109], palladium [73,105,112,[118][119][120] in many cases proceeded with good enantioselectivity and is a convenient method for the synthesis of tertiary phosphines. For example, the reaction of aryl iodides with secondary arylphosphines, catalyzed by chiral complex Pd((R,R)-Me-Duphos)(trans-stilbene), gives tertiary phosphines with enantioselectivity up to 88% ee [110,119] (Equation (83)).…”

Double asymmetric hydrogenation of conjugated dienes: a self-breeding chirality route for C2 symmetric 1,4-diols

“…In the latter case, two stereogenic centers are formed simultaneously in the first step and no influence on the diastereomeric product ratio should be expected when the enantiomeric excess of the catalyst is changed. 18 Significant changes in dr were otherwise observed in the hydrogenation of 1c upon variation of the ee of the catalyst precursor 5b (Figure 3), from dr = 1.0 with rac-5b to dr = 3.6 with 5b. These observations are in accord with a substrate decoordination between the generation of the first and second stereogenic centers, suggesting that path a is operating in the present hydrogenation reactions.…”

Accelerated and Enantioselective Synthesis of a Library of P‐Stereogenic Urea Phosphines

“…Asymmetric metal catalyzed hydrophosphination and phosphination is well known with palladium, platinum, and ruthenium metals in the presence of different types of bidentate chiral phosphine ligands. Glueck and co‐workers demonstrated that palladium can be used for enantioselective phosphination reaction in combination with ( S , S ) Me‐DUPHOS ligand (Figure ) . In their attempts to synthesize enantiopure P‐stereogenic phosphines (not urea containing), Glueck and co‐workers achieved 88 % enantiomeric excess ( ee ).…”