Study of the Configuration Stability of the Carbon – Zinc Bond, Direct Measurement of Enantiomeric Ratios, and Tentative Assignment of the Absolute Configuration in Secondary Organozinc Halides

Guijarro, Albert; Rieke, Reuben D.

doi:10.1002/(sici)1521-3773(20000417)39:8<1475::aid-anie1475>3.0.co;2-s

Cited by 21 publications

(5 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The aryl group would be installed using a Pd-catalyzed Negishi coupling of an organozinc reagent such as ( S )- 13 which could be obtained from the enantioenriched organolithium intermediate ( S )- 14 ( via transmetalation with ZnCl 2 ). Access to organolithium reagent ( S )- 14 is possible using s -BuLi/(−)-sparteine-mediated asymmetric deprotonation of N -Boc pyrrolidine 15 , as pioneered by Beak et al , Of note, the antipodal α-arylated pyrrolidines ( S )- 12 could be accessed using the (+)-sparteine surrogate or Alexakis diamine ( S , S )- 16 . , Other aspects of the route outlined in Scheme with encouraging precedent included the documented configurational stability of secondary organozinc reagents, the Pd-catalyzed Negishi couplings of achiral secondary organozinc reagents with aryl halides and Dieter and Li’s development of a CuCN-catalyzed Pd-coupling of lithiated N -Boc pyrrolidine with aryl iodides as a route to racemic α-arylated pyrrolidines …”

Section: Introductionmentioning

confidence: 99%

Enantioselective, Palladium-Catalyzed α-Arylation of N-Boc Pyrrolidine: In Situ React IR Spectroscopic Monitoring, Scope, and Synthetic Applications

et al. 2011

View full text Add to dashboard Cite

A comprehensive study of the enantioselective Pd-catalyzed α-arylation of N-Boc pyrrolidine has been carried out. The protocol involves deprotonation of N-Boc pyrrolidine using s-BuLi/(-)-sparteine in TBME or Et(2)O at -78 °C, transmetalation with ZnCl(2) and Negishi coupling using Pd(OAc)(2), t-Bu(3)P-HBF(4) and the aryl bromide. This paper reports several new features including in situ React IR spectroscopic monitoring of the process; use of (-)-sparteine and the (+)-sparteine surrogate to access products with opposite configuration; development of a catalytic asymmetric lithiation-Negishi coupling reaction; extension to a wide range of heteroaromatic bromides; total synthesis of (R)-crispine A, (S)-nicotine and (S)-SIB-1508Y via short synthetic routes; and examples of α-vinylation of N-Boc pyrrolidine using vinyl bromides exemplified by the total synthesis of naturally occurring (+)-maackiamine (thus establishing its configuration as (R)). In this way, the full scope and limitations of the methodology are delineated.

show abstract

Section: Introductionmentioning

confidence: 99%

Enantioselective, Palladium-Catalyzed α-Arylation of N-Boc Pyrrolidine: In Situ React IR Spectroscopic Monitoring, Scope, and Synthetic Applications

et al. 2011

View full text Add to dashboard Cite

show abstract

“…Nickel-catalyzed cross-coupling reactions of chiral alkylmagnesium and alkylzinc reagents have been studied at low temperatures, where racemization of the alkylmetal reagent is suppressed (Scheme ). , Hoffmann found that cross-coupling of Grignard reagents proceeds with retention of configuration . While, to the best of our knowledge, detailed studies of the stereochemical outcome of transmetalation from alkylzinc reagents and nickel catalysts have not been reported, Knochel has reported diastereoselective cross-coupling of a norbornylzinc reagent that procedes with retention of configuration. , In this report, we examine the nickel-catalyzed cross-coupling of alkylboranes, common reagents in sp 3 –sp 3 cross-coupling reactions that show robust stereochemical integrity at room temperature.…”

mentioning

confidence: 99%

Stereochemistry of Transmetalation of Alkylboranes in Nickel-Catalyzed Alkyl–Alkyl Cross-Coupling Reactions

Taylor

Jarvo

2011

J. Org. Chem.

View full text Add to dashboard Cite

show abstract

“…Despite the documented configurational integrity of secondary alkylzinc reagents, there have been no reports of the direct metalation of 1 with organozinc reagents to produce 3 . Alternatively, 3 should be readily accessed by treatment of 2 with ZnCl 2 .…”

mentioning

confidence: 99%

Enantioselective, Palladium-Catalyzed α-Arylation of N-Boc-pyrrolidine

et al. 2006

View full text Add to dashboard Cite

This communication discloses the first instance of the enantioselective Pd-catalyzed alpha-arylation of N-Boc-pyrrolidine. The methodology relies on Beak's sparteine-mediated, enantioselective deprotonation of N-Boc-pyrrolidine to form the 2-pyrrolidinolithium specices in high enantiomeric ratio (er). Transmetalation of this intermediate with zinc chloride generates the stereochemically rigid, 2-pyrrolidinozinc reagent, which was readily coupled to a variety of functionalized aryl halides at room temperature using a catalyst generated from Pd(OAc)2 and PtBu3-HBF4. A diverse array of 2-aryl-N-Boc-pyrrolidines was synthesized using this methodology, providing adducts consistently in a 96:4 er. A survey of the stoichiometry revealed that as little as 0.3 equiv of zinc could be used in the coupling reaction, and the 2-pyrrolidinozinc reagent was found to exhibit stereochemical stability up to 60 degrees C. The method allows for the most convergent and reliable preparation of a broad range of functionalized 2-aryl-N-Boc-pyrrolidines in high enantioselectivity, which is highlighted in this report by the enantioselective synthesis of (R)-nicotine.

show abstract

Study of the Configuration Stability of the Carbon – Zinc Bond, Direct Measurement of Enantiomeric Ratios, and Tentative Assignment of the Absolute Configuration in Secondary Organozinc Halides

Cited by 21 publications

References 26 publications

Enantioselective, Palladium-Catalyzed α-Arylation of N-Boc Pyrrolidine: In Situ React IR Spectroscopic Monitoring, Scope, and Synthetic Applications

Enantioselective, Palladium-Catalyzed α-Arylation of N-Boc Pyrrolidine: In Situ React IR Spectroscopic Monitoring, Scope, and Synthetic Applications

Stereochemistry of Transmetalation of Alkylboranes in Nickel-Catalyzed Alkyl–Alkyl Cross-Coupling Reactions

Enantioselective, Palladium-Catalyzed α-Arylation of N-Boc-pyrrolidine

Contact Info

Product

Resources

About