Platinum-Catalyzed Asymmetric Alkylation of Bis(isitylphosphino)ethane: Stereoselectivity Reversal in Successive Formation of Two P−C Bonds

Abstract

Alkylation of the bis(secondary) phosphine IsHP(CH 2 ) 2 PHIs (1; Is = isityl = 2,4,6-(i-Pr) 3 C 6 H 2 ) with 2-(bromomethyl)naphthalene using 10 mol % of the catalyst precursor Pt((R,R)-Me-DuPhos)-(Ph)(Cl) and the base NaOSiMe 3 selectively yielded meso-IsP(CH 2 Ar)(CH 2 ) 2 P(CH 2 Ar)(Is) (2; Ar = 2-naphthyl; dr = meso/rac ratio = 3.4:1). Half-alkylated IsP(CH 2 Ar)(CH 2 ) 2 PH(Is) (3), an intermediate in this reaction, was prepared from 1 by deprotonation (s-BuLi) and alkylation with 2-(chloromethyl)naphthalene. Analysis of the observed diastereo-and enantioselectivity in the Pt-catalyzed alkylations of 1 and 3 yielded quantitative information on the stereoselectivity of both P-C bond-forming steps. The first alkylation (1 f 3) resulted in diastereoselective formation of a tertiary phosphine stereocenter (∼2:1 ratio). In the second alkylation (3 f 2), however, both (R P )-3 and (S P )-3 (the label refers to the configuration of the tertiary phosphine) selectively formed meso-2, instead of (R,R)-2 or (S,S)-2, respectively (the ratios were ca. 3:1 and 7:1). Thus, the tertiary phosphine in 3 favored alternation of stereochemistry in the alkylation of the secondary phosphine (substrate control with negative cooperativity). Platinum-catalyzed alkylation of IsPH(CH 2 ) 2 OSi(iPr) 3 (6) gave IsP(CH 2 Ar)(CH 2 ) 2 OSi(i-Pr) 3 (9) in a 1.5:1 enantiomeric ratio (er). A related reaction of IsPH(CH 2 ) 2 OSiMe 3 (4) gave a mixture of IsP(CH 2 Ar)(CH 2 ) 2 OR (R = SiMe 3 (7); R = H (8)), while alkylation of IsPH(CH 2 ) 2 OH (5) gave 8 in about 2:1 er. Thus, the nature, and even the absolute configuration, of the pendant group X three bonds from the reactive phosphorus center in the substrates IsHP(CH 2 ) 2 X (X = PHIs (1), P(CH 2 Ar)(Is) (3), OSiMe 3 (4), OH (5), OSi(i-Pr) 3 (6)) had a strong influence on the selectivity of Pt-catalyzed phosphorus alkylation. Possible mechanistic explanations for this substrate control are discussed.

Asymmetric Electrophilic Reactions in Phosphorus Chemistry

“…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)).…”

“…Me2S or BH3 THF) (Equation (115)) [165,166]. (115) A number of optically pure α-and β-hydroxyalkylphosphine boranes were prepared using a three-step method from readily available adamantyl H-phosphinates. First, an one-pot reaction gave enantiomerically pure tertiary hydroxyalkylphosphine oxides in good yield and high ee.…”

“…Then, the treating the product with excess BH3 resulted in the formation of phosphine borane, with high stereospecificity (Equation (116)). Adamantyl H-phosphinates as precursors of P-stereogenic ligands (115) A number of optically pure αand β-hydroxyalkylphosphine boranes were prepared using a three-step method from readily available adamantyl H-phosphinates. First, an one-pot reaction gave enantiomerically pure tertiary hydroxyalkylphosphine oxides in good yield and high ee.…”

“…Catalytic asymmetric alkylation of bis(secondary phosphines) with benzyl bromide using NaOSiMe 3 base and Pt((R,R)-Me-Duphos)(Ph)(Cl) led to the formation of bis-tertiary phosphines. Catalytic alkylation of bis-phosphines with 2-(bromomethyl) naphthalene using 10 mol% of the Pt((R,R)-Me-DuPhos)(Ph)(Cl) catalyst and NaOSiMe 3 allowed to obtain diastereomerically pure bis(tertiary)-phosphines as shown in Equations(80) and(81) [110][111][112][113][114][115][116].…”

Asymmetric C-P bond formation via hydrophosphination activated by palladacycles : synthesis of chiral tertiary phosphines

“…However, some efforts have been made towards catalytic synthesis of chiral diphosphines. Toste et al reported a Ru-catalyzed enantioselective synthesis of P-stereogenic phosphines via alkylation which included one example of a PCP diphosphine with chiral center at phosphorus: 33b,c 101 However, the diastereo-and enantioselectivities were quite low. In preceding contributions, our group has reported the asymmetric synthesis of chiral diphosphines promoted by palladacycles.…”