beta-Isosparteine

Highly enantioselective (-)-sparteine-mediated lateral metalation-functionalization of remote silyl protected ortho-ethyl N,N-dialkyl aryl O-carbamates.[Pubmed: 25521308 ]

J Org Chem. 2015 Apr 3;80(7):3368-86.

METHODS AND RESULTS:
We report the enantioselective, lateral deprotonation of ortho-protected or functionalized tertiary N,N-dialkyl aryl O-carbamates 5-7 (Scheme 2 ) and meta-protected carbamates 14, 15, and 20 (Schemes 5 and 7 ) by s-BuLi/(-)-Sparteine and subsequent quench with a variety of electrophiles to give products 11-13 and 16, 17, and 21 in yields up to 96% and enantiomeric ratios up to 99:1. The influence of organolithium reagents, ratio of organolithium/(-)-Sparteine pair versus N,N-dialkyl aryl O-carbamate starting materials, temperature, solvents, electrophiles, substituents located ortho or meta to the O-carbamate moiety, and O-carbamate N-substituents was investigated. The identical absolute configuration of the stereogenic center of the major enantiomers of the products, as established by single-crystal X-ray analysis for substrates (S)-11c, (S)-19, and (S)-21a, provides evidence for a consistent stereochemical course in the enantioselective deprotonation. Mechanistic investigations, including an estimate of the configurational stability of the benzyllithium species 9 (starting from 12e; Scheme 8 ) and 23 (starting from 17e; Scheme 9 ), both derived by tin-lithium exchange, and 24 (starting from 20; Scheme 9 ) are reported.
CONCLUSIONS:
The experimental results, together with semiempirical molecular orbital calculations (PM3/SMD), are consistent with a process in which enantioinduction occurs in the deprotonation step (Scheme 11 ).

J Am Chem Soc. 2010 Oct 6;132(39):13922-7.

Synthesis of P-stereogenic compounds via kinetic deprotonation and dynamic thermodynamic resolution of phosphine sulfides: opposite sense of induction using (-)-sparteine.[Pubmed: 20843035]

A systematic study of the asymmetric deprotonation of a dimethyl-substituted phosphine sulfide using organolithium bases in the presence of (-)-Sparteine has been carried out.
METHODS AND RESULTS:
Use of nBuLi and (-)-Sparteine in Et(2)O at -78 °C gave trapped adducts in ∼88:12 er via a kinetically controlled process that was successfully predicted using a computational approach at the B3LYP/6-31+G(d) level. This initial kinetic enantioselectivity could be enhanced up to 97:3 er by trapping the lithiated intermediate with a prochiral electrophile (e.g., pivaldehyde or tBuPCl(2)). In addition, it was found that the R(P) and S(P) stereoisomers of the lithiated methylphosphine sulfide could interconvert at temperatures above 0 °C. Such interconversion is unprecedented and differs from the configurational instability of organolithiums that are stereogenic at a lithiated carbon atom. The major, thermodynamically preferred diastereomeric (-)-Sparteine-complexed lithated phosphine sulfide was investigated by X-ray crystallography and computational methods at the B3LYP/6-31+G(d) level. Through the interconversion of the R(P) and S(P) stereoisomers of the lithiated methylphosphine sulfide, a novel dynamic thermodynamic resolution of a racemic lithiated phosphine sulfide has been developed. Thus, the phosphine sulfide was lithiated with nBuLi, and then (-)-Sparteine was added. After equilibration at 0 °C for 3 h, electrophilic trapping generated an adduct in 81:19 er with the configuration opposite to that obtained under kinetic control.
CONCLUSIONS:
Thus, the methodology provides access to P-stereogenic compounds with the opposite sense of induction using (-)-Sparteine as the ligand simply by changing the reaction conditions (kinetic or thermodynamic control).

Org Biomol Chem. 2014 Dec 14;12(46):9357-65.

Revisiting the sparteine surrogate: development of a resolution route to the (-)-sparteine surrogate.[Pubmed: 25297971]

The improved performance of the sparteine surrogate compared to sparteine in a range of applications has highlighted the need to develop an approach to the (-)-Sparteine surrogate, previously inaccessible in gram-quantities.
METHODS AND RESULTS:
A multi-gram scale, chromatography-free synthesis of the racemic sparteine surrogate and its resolution via diastereomeric salt formation with (-)-O,O'-di-p-toluoyl-l-tartaric acid is reported. Resolution on a 10.0 mmol scale gave the diastereomeric salts in 33% yield from which (-)-Sparteine surrogate of 93 : 7 er was generated.
CONCLUSIONS:
This work solves a key limitation: either enantiomer of the sparteine surrogate can now be readily accessed.