Sparteine stereochemistry

The ligand synthesis is straightforward, using amino alcohols as the source of chirality in the oxazoline ring, whereas the stereochemistry in the phospholane ring is controlled by an enantioselective deprotonation using sparteine (Scheme 29.2). 

By careful optimization, Widdowson and coworkers were able to show that methoxy-methyl ethers of phenols are better substrates for alkyllithium-diamine controlled enan-tioselective deprotonation, and (—)-sparteine 362 is then also the best ligand among those surveyed the BuLi-(—)-sparteine complex deprotonates 447 to give, after electrophilic quench, compounds such as 449 in 58% yield and 92% ee (Scheme 180) . Deprotonation of the anisole complex 410 (see Scheme 169) under these conditions gave products of opposite absolute stereochemistry with poor ee. 

A problem with (—)-sparteine 362 is its lack of availability in both enantiomeric forms. Reversed selectivity in the generation of planar chirality has been achieved by second lithiations (see Schemes 163 and 171) and a remarkable modification of this strategy works with arenechromium tricarbonyls. By using excess BuLi (sometimes f-BuLi is required) in the presence of sparteine 362, a doubly lithiated species 450 may be formed from 448. The formation of the doubly lithiated species may be confirmed by double deuteriation with excess D2O. However, other electrophiles react selectively only once and give products of opposite absolute stereochemistry from those formed after monolithiation, if in rather low yield. Presumably, the first lithiation, which is directed by (—)-sparteine, produce an organolithium 448 whose complexation with (—)-sparteine remains favourable. The second lithiation must produce a less stable organolithium—one which cannot form a... 

Wiewiorowski, M., Pieczonka, G. and Skolik, J. 1977. Futher smdies on the stereochemistry of sparteine, its isomers and derivatives. Part 1. Synthesis, structure and properties of 16,17-endo-methylene-lupaninium perchlorate, 17 3-methyllupanine and 17(3-methyl sparteine. Journal of Molecular Structure, 40 233. 

Retention in the reactions of 15 is established both from presumed retention in the Sn-Li exchange step of a stannylation-destannylation sequence and by evidence that the s-BuLi-(-)-sparteine complex used to make the organolithium reliably removes the pro-/ proton adjacent to a carbamate (see below for crystallographic evidence involving a similar compound).11 The stereochemistry of the products 16, almost all formed essentially in enantiomerically pure form, was proved for the C02 adduct and the Mel adduct by comparison with known compounds. The only electrophiles for which incomplete retention of stereochemistry has been observed are the benzylic or allylic halides. These probably react in part by single electron transfer SE1 mechanisms, rather than by partial SE2inv.15 For example, 15 reacts with allyl bromide to give 16 (E = allyl) with only 42% ee. 

The formation of diastereoisomerically pure complexes of 90 with (-)-sparteine is also controlled by crystallisation. Treatment of the indene 89 with BuLi and (-)-sparteine in ether gives, on warming, a yellow precipitate which reacts with carbonyl electrophiles to provide the products 91 typically with good regioselectivity and >95% ee.52 An X-ray crystal structure proved the stereochemistry of the intermediate complex to be that shown as 90b, and hence proved the stereochemical course of the substitution (see section 6.1). The complex is readily decomposed by THF, in the presence of which it rearranges to a racemic V allyllithium. 

It has only recently become possible for synthetic chemists to use the stereochemistry that reactions like this possess, as seen with the reagent 5.10 created using butyllithium and (-)-sparteine. The explanation offered in this case is that reactive electrophiles, those not requiring Lewis acid catalysis, are apt to react with inversion of configuration, while those that need to coordinate to the metal to experience some Lewis acid catalysis, are apt to react with retention of configuration, because the electrophile is necessarily being held on the same side as the metal. 

Thus, the two enantiomers of 92 can be synthesized from (—)sparteine by switching the stereochemistry of the double bond of cinnamyl alcohol from to Z [128]. 

This stereochemical analysis was further confirmed by the close resemblance between the IR Bohlmatm bands of sparteine and 2-dehydro-2-phenylsparteine furthermore the IR spectrum of 14-dehydro-15-phenylsparteine showed distinguishing features in the same region, in accordance with the different orientation of the N-16 lone pair. The proposed stereochemistry is also in agreement with experimental observations that demonstrated that the 2-dehydro-2-substituted sparteine derivatives are reduced by sodiiun borohydiide via the P-plane, while 14-dehydro-15-phenylsparteine is reduced via the a-plane, which means that, in both instances, reduction takes place on the least hindered side of the corresponding iminium cations. 

Polish chemists have continued to study the stereochemistry of sparteine and its derivatives in relation to the all-chair conformation (15) ( cisoidal ) and the chair,chair, boat, chair conformation (16) ( transoidal ). Infrared studies indicated that the hydrate of 10-oxosparteine hydrochloride is in the transoidal conformation, cf. (16), whereas the corresponding acid salts of 15-... 

In 2003, Stoltz at CalTech described a palladium-catalyzed oxidative Wacker cyclization of o-allylphenols such as 55 in nonpolar organic solvents with molecular oxygen to afford dihydrobenzofurans such as 56.44 Interestingly, when (-)-sparteine was used in place of pyridine, dihydrobenzofuran 56 was produced asymmetrically. The ee reached 90% when Ca(OH)2 was added as an additive. Stoltz considered it a stepping stone to asymmetric aerobic cyclizations. In 2004, Mufiiz carried out aerobic, intramolecular Wacker-type cyclization reactions similar to 55—>56 using palladium-carbene catalysts.45 Hiyashi et al. investigated the stereochemistry at the oxypalladation step in the Wacker-type oxidative cyclization of an o-allylphenol. Like o-allylphenol, o-allylbenzoic acid 57 underwent the Wacker-type oxidative cyclization to afford lactone 58.47... 

The ligand 108 has activity as an external controller of stereochemistry in the enantioselective addition of methyllithiiun to imines derived from veratralde-hyde with up to 41% ee [87]. (-)-Sparteine (19)-mediated reaction of organo-hthium reagents afforded isoquinoUne alkaloid 107 directly from 3,4-dihydroi-soquinoline 106 with up to 47% ee (Scheme 32) [88]. 

Taylor and Wei have reported an excellent alternative way to generate the ben-zylhthiums, starting with 2-substituted styrenes. Addition of w-BuIi to 2-substi-tuted styrenes in the presence of (-)-sparteine successfully afforded benzyllith-iums which were trapped with CO2 to give products with high enantioselectivity, the absolute stereochemistry of the products not being determined [Eq. (40)] [95]. 

Widdowson has exploited the asymmetric deprotonation of 183 in a synthesis of a protected version 191 of the biaryl component of vancomycin, actinoidinic acid (Scheme 48) [110, 111]. One of the rings derives from an arenechromiiun tricarbonyl with stereochemistry controlled by asymmetric lithiation. The most readily lithiated position of 183, between the two methoxy groups, first needed blocking. Enantioselective lithiation and chlorination of 184 gave 186 (TMEDA was needed to displace sparteine from 185 and restore reactivity towards a poor electrophile). Suzuki coupling of 187 with the boronic acid 188 transfers planar... 

Stereoselective intramolecular alkene hydrosilylation followed by Si-C cleavage is a valuable route to diols both relative - and absolute stereochemistries may be controlled. The rates of the fundamental steps in the [Rh(diphosphine)] catalysed reactions are controlled to some extent by the nature of the diphosphine. From deuterium-labelling studies a silyl insertion mechanism becomes apparent. Whether such mechanisms are applicable to C=0 hydrosilylation versions of this reaction is not yet known. Other highly enantioselective (83-96% ee) C=0 silylations use 13,162 but attempts to use readily available (-)-sparteine as a rhodium ligand are much less successful (5-8% ee).i Further details of the spectacularly effective MOP ligand 14 have appeared.i Optical purities of 93-96% ee are realised using 0.01 mol% Pd2( x-Cl)2( n-C3H5)2 and 0.02 mol% 14 for terminal alkenes and norbomene. 

Kizirian, J.-C. (2010) Mechanism and Stereochemical Eeatures in Asymmetric Deprotonation Using RLi/ (—)-Sparteine Bases, in Topics in Stereochemistry, Stereochemical Aspects of Organolithium Compounds (eds. Gawley, R. E., Siegel, J. S.), Verlag Helvetica Chimica Acta, Zurich, pp. 189—251. 

With the natural product (—)-sparteine as chelating N-donor ligand, asymmetric Pd catalysis can be achieved in this way via kinetic resolution of PhCH(OH)Me with krei ratios up to 25. BackvalP obtained oxidative 1,4-addition of nucleophiles to dienes with good control of stereochemistry in the product. The hydroquinone/benzoquinone pair is the redox partner that couples the Pd catalyst with air as primary oxidant. 

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