Cascade stereoselectivity

Coquerel Y, Bensa D, Moret V, Rodriguez J (2006) Synthetic studies on the MARDi cascade stereoselective preparation of sulfonyl-substituted seven-membered rings. Synlett 2751-2754... 

Radical cascades that feature a 7-exo acyl radical cyclization followed by a 6-exo or 5-exo alkyl radical cyclization proceed with very good yields and diastereoselectivities. Two examples are shown in Reaction (80), where treatment of 100 with E3B, air, and (TMS)3SiH provided the tricycle 101 in excellent yields as a single diastereomer. Interestingly, the bulky silyl ether moiety is not required to achieve stereoselectivity in this process. 

Figure 10.18 Enzymatic in situ generation of dihydroxyacetone phosphate from fructose 1,6-bisphosphate (b), with extension to an in vitro artificial metabolism for its preparation from inexpensive sugars alongthe glycolysis cascade (a), and utilization for subsequent stereoselective carbon-carbon bond formation using an aldolase with distinct stereoselectivity (c).

Neier and coworkers have shown that piperidine diones (e.g., 105) can be prepared stereoselectively using a cascade Diels-Alder/acylation reaction of ketene acetal 104 <96T(52)11643>. 

In addition, Wu and Li recently have developed an efficient rhodium-catalyzed cascade hydrostannation/conjugate addition of terminal alkynes and unsaturated carbonyl compounds in water stereoselectively (Scheme 4.5).88... 

Recently, Denmark and coworkers have developed a new strategy for the construction of complex molecules using tandem [4+2]/[3+2]cycloaddition of nitroalkenes.149 In the review by Denmark, the definition of tandem reaction is described and tandem cascade cycloadditions, tandem consecutive cycloadditions, and tandem sequential cycloadditions are also defined. The use of nitroalkenes as heterodienes leads to the development of a general, high-yielding, and stereoselective method for the synthesis of cyclic nitronates (see Section 5.2). These dipoles undergo 1,3-dipolar cycloadditions. However, synthetic applications of this process are rare in contrast to the functionally equivalent cycloadditions of nitrile oxides. This is due to the lack of general methods for the preparation of nitronates and their instability. Thus, as illustrated in Scheme 8.29, the potential for a tandem process is formulated in the combination of [4+2] cycloaddition of a donor dienophile with [3+2]cycload-... 

Dihydronaphthalenes are remarkable substrates for the combined C-H activation/Cope rearrangement, but under certain circumstances, further cascade reactions can occur. This was seen in the Rh -DOSP -catalyzed reaction of vinyldiazoacetate 26 with dihydronaphthalene 25 (Equation (35)).96 In this case, the isolated product was the formal C-H insertion product. The reaction proceeded through a combined C-H activation/Cope rearrangement to form 27, followed by the reverse Cope rearrangement. As both steps were highly stereoselective, the formal C-H insertion product 28 was produced with very high stereoselectivity (>98% de, 99.6% ee).96... 

Novel aldol-type reactions under Cinchona-deriwed chiral thiourea catalysis was reported by Wang et al. [78]. In their report, a novel cascade Michael-aldol reaction was presented. The reaction involves a tandem reaction catalyzed via hydrogen-bonding with as little as 1 mol% catalyst loading to generate a product with three stereogenic centers (Scheme 28). hi the reaction of 2-mercaptobenzaldehyde 128 and a,P-unsatnrated oxazolidinone 129, the desired benzothiopyran 130 was formed smoothly in high yield and excellent stereoselectivity. 

Coquerel Y, Eilippini MH, Bensa D, Rodriguez J (2008) The MARDi cascade a Michael-initiated domino-multicomponent approach for the stereoselective synthesis of seven-membered rings. Chem Eur J 14 3078-3092... 

Bicyclic ester 100 forms in analogy to isomeric ester 65 (Section 2.4.1.1) (07JOC5608). /l-Phenylethylamine 101 undergoes palladium-catalyzed direct aromatic carbonylation, thus providing another synthesis of benzo-lactam 78b (06JOC5951). A stereoselective nitro-Mannich/lactamization cascade of y-nitro ester and cyclic imine affords polysubstituted lactam 102 (08OL4267). 

The total synthesis of litseaverticillols D, F and G (172 and 173), which are natural products with anti-HIV activity, was achieved recently via a singlet oxygen initiated cascade proposed to be biomimetic (Scheme 64). Finally, allylic alcohols 174a and 174b (Scheme 64) were isolated in a 4/1 ratio via a stereoselective singlet oxygen ene reaction. Stereoisomer 174a is an intermediate in the synthetic route of staurosporine, which is a bioactive alkaloid with hypotensive, antimicrobial and cell cytotoxic properties. 

Apart from ATRP, the concept of dual initiation was also applied to other (controlled) polymerization techniques. Nitroxide-mediated living free radical polymerization (LFRP) is one example reported by van As et al. and has the advantage that no further metal catalyst is required [43], Employing initiator NMP-1, a PCL macroinitiator was obtained and subsequent polymerization of styrene produced a block copolymer (Scheme 4). With this system, it was for the first time possible to successfully conduct a one-pot chemoenzymatic cascade polymerization from a mixture containing NMP-1, CL, and styrene. Since the activation temperature of NMP is around 100 °C, no radical polymerization will occur at the reaction temperature of the enzymatic ROP. The two reactions could thus be thermally separated by first carrying out the enzymatic polymerization at low temperature and then raising the temperature to around 100 °C to initiate the NMP. Moreover, it was shown that this approach is compatible with the stereoselective polymerization of 4-MeCL for the synthesis of chiral block copolymers. 

Chiral l,3-dioxin-4-ones photochemically react intermolecular with (cyclic) ethers, acetals, and secondary alcohols to give the addition products in reasonable yields. The radical addition was completely stereoselective at C-6 of the heterocycle <1999EJO1057>. The exocyclic diastereoselectivity, where relevant, was about 2 1 (Equation 30). In analogy, an intramolecular cascade reaction of a 1,3-dioxin -one derived from menthone was used to get a terpenoid or a steroid framework in optically active form <1997JA1129, 1999JA4894>. 

Yttrium-catalyzed cascade cyclization/hydrosilylation of 3-(3-butynyl)-l,5-hexadienes was stereospecific, and syn-19 (R =Gy, R = OGPh3) underwent cascade cyclization/hydrosilylation to form 80b (R = Gy, R = OGPh3) in 97% yield as a single diastereomer (Scheme 20). The regio- and stereoselective conversion of syn-19 to 80b was proposed to occur through an initial 5- x -intramolecular carbometallation via a chairlike transition state that resembles alkenyl olefin eomplex syn- m. followed by S-exo intramolecular carbometallation via a boatlike transition state that resembles alkyl olefin complex boat-llm. The second intramolecular carbometallation presumably occurs via a boatlike transition state to avoid the unfavorable 1,3-interaction present in the corresponding chairlike transition state (Scheme 20). 

The sequential treatment of ( , )-l-tosylamido-2, 4-alkadienes with n-butyl-lithium and propynyliodonium triflate 30 results in a cascade addition/bicy-clization sequence leading to bicyclic N-tosyldihydropyrroles 39 (Scheme 60) [165,166]. These transformations are completely stereoselective for the cis-isomers, and appear to proceed by intramolecular addition of alkylidenecarbene intermediates to the C2-C3 double bond of the pentadienyl chain to give azabi-cyclo[3.1.0]hexenes, which rearrange to 39 through diyl radical species. 

Oxidatively generated oxocarbenium ions have been used for intramolecular epoxide activation. Cascade reactions to form oligotetrahydrofuran products that demonstrated a strong preference for the exo-cyclization pathway were achieved in good yields when disubstituted epoxides were used as substrates. High stereoselectivity was observed in these reactions, with complementary diastereomers being formed from diastereomeric (g) epoxides.257... 

Lewis acid-mediated endo -cyclization of trimethylsilylmethylenecyclopropylimines provides a stereoselective route to indolizidines via a novel cascade sequence including (g) a [l,2]-hydride shift (Scheme 56).91... 

Radical cyclization of 405 led to the dimethylene tricyclic /3-lactam 406 in a cascade sequence of steps. Radical procedures have been used extensively and have the advantages of stereoselectivity in the cyclization step from relatively simple starting materials. A disadvantage is the sometimes relatively low yield <1999TL5391, 2000TL10347>. Other examples of the use of radical cyclization processes are given in Sections 2.04.11.1.1 (ii), 2.04.11.2.2, 2.04.11.3, and 2.04.11.4. 

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