Stereoselectivity 4+2 annulations

Table 2. Stereoselective Annulation with 1,3-Asymmetric Induction Using Ethylaluminum Dichloride as Lewis Acid...

O. W. Cydic alkenenitriles synthesis, conju- 490 gate addition, and stereoselective annulation. 

The [3 + 2] stereoselective annulations using allylsilanes were also applied to the syntheses of furans (equation 59)156-162 7V-acylpyrrolidines163,164, a 2-thiabicyclo[2.2.1] hept-5-ene-3-spiro-2/-indan-l/-one165 and A2-isoxazoline derivatives166,167. 

Silyloxybenzothiopyiylium-Salts A New Tool for the Stereoselective Annulation of S-Heterocycles... 

In 2012, Alexakis and co orkers disclosed the first stereoselective annulation reaction between ynals and a-cyano-l,4-diketones which is mediated by a catalytic amount of a triazolium salt precatalyst and a weak carboxylate base. This transformation proceeds smoothly under mild reaction conditions and generates three contiguous stereogenic centers, one of which is a quaternary acetal carbon, and affords privileged bicyclic scaffolds in 61-90% yields with up to 20 1 diastereomeric preference. A mechanistic rationalization for the NHC-catalyzed annulation of a-cyano-l,4-diketones with ynals is proposed as the following. Initially, the free carbene condenses with a molecule of ynal to form the key d,p-unsaturated acylazolium intermediate followed by a direct nucleophilic conjugate addition of 1,4-diketone. Subsequent intramolecular H-migration and an irreversible lactonization furnish the observed bicyclic product and liberate free carbene for the next catalytic cycle (Scheme 7.98). 

From the first attempt to reevaluate the high potential of levoglucosenone as the perfect model molecule for various types of stereoselective annulations came from the Isobe approach to reserpine (50), which is a classic example of assembling the required stereochemistry as well as a specific ring sequence. This is illustrated in Scheme 11. 

Figure 3.17 Synthesis of a stereopure linear HIV-1 protease inhibitor P2-building block via arylation of ethylene glycol vinyl ether and a subsequent stereoselective annulation.

In 2010, Scheldt and coworkers reported cooperative N-heterocyclic car-bene/Lewis acid catalysis for highly stereoselective annulation reactions. This cooperative catalysis process integrating titanium(iv) and triazolium-derived NHCs allowed the synthesis of ds-cyclopentenes 69 with a broad substrate scope and high enantioselectivity (Scheme 20.33). 

Recently, Scheldt and co-workers [86] introduced the Lewis acid/NHC cocatalysis, which opens new opportunities for NHC-catalyzed reactions. For example, these authors reported a cooperative NHC/Lewis acid catalysis for the stereoselective annulations of enals with enones (Scheme 7.68). 

Addition of enals to enones to give cA-cyclopentenes is an example of a stereoselective annulation with homoenolates. Catalysed by NHCs and Lewis acids such as Ti(OPr-t)4, the cooperative nature of these species has been explored in a DFT study Another DFT study into the NHC-catalysed cycloannulation of the homoeno- 0 late derived from butenal with pentenone has examined pathways to cyclopentene and cyclopentanone derivatives and the effect of the presence of DABCO on proton transfer steps. ... 

J. E. Backvall, New J. Chem., 1990, 14, 447-452. Stereoselective Annulations Via Palladium-Catalyzed Reactions. 

TiCU-mediated Prins cyclization of S, - and unsaturated ketones offers a simple stereoselective annulation method for construction of thermodynamically stable, tertiary cyclohexanols with incorporation of a cis-chloro substituent [327] (Scheme 14.144). This reaction showed the potential usefulness in the synthesis of halogenated terpenes or some other types of functionalized cyclohexanols. 

Ring closure of functionalized dienones occurs again in 1,4-fashion to give an annulated six-membered ring. Both Lewis acid (ethylaluminum dichloride) and fluoride ion can be employed, but the chemical yield of this particular cyclization is low and no stereoselection regarding the position of the vinyl side chain was achieved35. 

Stereoselective Ring Annulations by Intramolecular 1,6-Addition of an Allylsilane Function... 

Stereoselective d.v-annulations of cyclopcntenones arc, however, possible using these procedures employing 1,3- or 1,4-bisMichael donors. 

Loh and coworkers used a combination of a carbonyl-ene and an oxenium-ene reaction for the synthesis of annulated tetrahydropyrans 1-61, using methylenecyclo-hexane 1-60 as substrates (Scheme 1.16) [15]. The most appropriate catalyst for this reaction with the aldehydes 1-59 turned out to be In(OTf)3, which furnished the desired products in good to excellent yields and high stereoselectivity [16]. 

The novel [6+2] annulation approach developed by the Takeda group has also been included in a threefold anionic/pericyclic process (Scheme 2.149) [340]. The reaction leads to functionalized eight-membered rings 2-659 in a highly stereoselective manner, starting from acylsilanes 2-656 and 3-(trimethylsilyl)vinyl-lithium (2-657). After 1,2-addition and 1,2-Brook rearrangement, the cyclobutane 2-... 

Substituted (5R,6A,)-6-(dimethyl(phenyl)silyl)-2-phenyldihydropyrazolo[l,2- ][l,2,4]triazole-l,3(2//,5//)-dione 716, synthesized via the [3+2] annulation of a-substituted allylic silanes 715 with PTAD, were oxidized to the corresponding hydroxy substituted urazoles 717. This work shows that allylsilanes with a single substituent at the allylic carbon undergo exclusive stereoselective [3+2] annulation (Scheme 114) <2007TL6671>. 

Watt and Drummond, were considered to be inert for C-C bond forming reactions. However, by the expedient of transmetallation to Cu, Ni, Zn, Li, and Al, methodologies for the stereoselective synthesis of olefins and dienes, as well as unusual heterocycles, aromatics and their ring-annulated products are now available which are beginning to make impact on material science, e. g. synthesis of pentacenes and polyphenylenes. Takahashi and Li provide evidence that, with further developments in transmetallation and handling the zirconacycles outside of the Schlenk tube techniques, synthetic utility will increase and new catalytic reactions will be developed. 

The azatriquinane 36a which may be regarded as an annulated bis-pyrrolizine readily undergoes stereoselective hydrogenation in presence of rhodium on alumina, leading to the fully saturated tricyclic compound with a trans relative orientation between the benzyl group and the two hydrogen atoms located on the two other junctions carbon atoms <2005JA1352>. 

Unlike with sodium borohydride (see Section 11.01.5.2), pyrrolizin-3-one 2 reacts with lithium aluminohydride mainly as an amide. No conjugate addition occurs, and only the reductive lactam cleavage takes place to give stereoselectively the (Z)-allylie alcohol 77. Similarly, benzo-annulated pyrrolizin-3-one 17 gives the corresponding benzylic alcohol 78. The same reactivity was observed with organometallics such as methyllithium which gives exclusively the tertiary (Z)-allylic alcohol 79 (Scheme 7). 

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