Domino reduction

Scheme 3.6. Samarium(ll)iodide-promoted domino reductive fragmentation/aldol reaction.

Scheme 7.9. Domino reduction/Wittig-Horner olefination process of aspartates.

Scheme 7.14. Domino reduction/nucleophilic cyclization procedure in the synthesis of diazonamide A (7-43).

Scheme 7.20. Zn-mediated domino reduction/biscyclization process in the total synthesis of (-)-strychnine (7-76).

Scheme 7.44. Sml2-promoted domino reductive desulfuration/reductive coupling process of lactams 7-166 with an aldehyde.

A domino reduction-aldol reaction of ketones with methyl acrylate produces tertiary alcohols bearing an ester group (51) in high ee and de.151 Using a diphosphine- modified copper fluoride complex in the presence of phenylsilane, the method avoids having to preactivate the nucleophile prior to the C—C bond-forming step. 

Samarium(II) iodide has been proven to be an efficient reagent to initiate radical processes that can be utilized in domino reactions. In 2001, Schwartz and coworkers [16] reported a domino reductive fragmentation and aldol reaction with 1,4-diketones promoted by Sml2 to afford the ring contracted products. The Reissig... 

Domino reduction/aldol cydization was applied for the synthesis of ( )-fredericamydn A 44, a potent antitumor and antibiotic agent, by Kelly et al. [18] in 1988 (Scheme 9.10). DIBAL-H (diisobutylaluminum hydride) reduction of lactone 45 afforded an intermediate 46 having both enolate and aldehyde. Subsequent cychzation via aldol reaction gave a diastereomeric mixture of spiro hydroxy ketone 47, which was further converted into ( )-fredericamycin A 44 by sequential organic transformations. A similar strategy was employed by Mehta et al. [19] for the synthesis of bicyclo[3.3.1]nonan-9-one core of hyperforin, an antidepressant. 

Scheme 9.13 Copper-catalyzed enantioselective domino reductive aldol reaction.

Scheme 9.14 Domino reductive aldol or Michael cyclization.

Scheme 9.16 Domino reductive conjugate reduction/Ireland-Claisen rearrangement.

Pyrrolizidinones have been found to be potent anti-inflammatory and antidepressant drugs [36]. Recently, Sukhorukov et al. developed a novel domino reductive ring-opening/double cychzation method for the synthesis of pyrrolizidinone 89, which is considered as a highly potent second-generation phospho diesterase IVb inhibitor. 

Scheme 9.17 Domino reductive ring-opening/double cyclization synthesis of phosphodiesterase (PDE) IV inhibitor.

Reduction-triggered pericyclic reaction has been used for the biomimetic total synthesis of endiandric acids A-G [72]. Endiandric acids are polycychc natural products isolated from the Australian plant Endiandra introrsa and exist naturally as a racemic mixture which is found to have very high antibacterial effect [73]. In 1980, Black and coworkers [74] proposed a hypothesis that these polycyclic systems are formed in nature by a series of electrocycUzation reactions. On the basis of this hypothesis, Nicolaou et al. [72c] in 1982 reported an excellent domino reduction/electrocyclization process for the synthesis of endiandric acid A 127 (Scheme 9.25). Selective hydrogenation using a Lindlar catalyst of diacetylenic diol 123 afforded the bicyclic diol 126. The reaction presumably proceeds via polyene 124, which then undergoes a spontaneous 8 [i-electrocyclization to give 125. It follows a second 6n-electrocyclization to afford bicyclic 126, which is further converted to endiandric acid A 127. 

Scheme 9.25 Synthesis of endiandric acid A by domino reduction/double electrocyclization.

Scheme 10.26 Domino reductive Michael/aldol reaction.

Riant developed a versatile methodology for the diastereo- and enantioselective domino reductive aldol cycHzation reaction of functionabzed a.fJ-unsaturated esters 147 into the corresponding bicyhc domino products 148 in high yields and enantios-electivities. The reaction was catalyzed by a Cu(I) complex of chiral bisphosphine 146 in the presence of phenylsilane as reductant The product 148 with three contiguous stereocenters was formed with high diastereoselectivities. The stereoselectivity of the process increased with the steric hindrance of the ester moiety, since the best results were obtained with the tert-butyl esters (Scheme 11.31) [50]. 

Scheme 11.31 Domino reductive aldol cyclization of functionalized a,P-unsaturated ester [50].

Scheme 7.20 Domino reductive amination catalysed by chiral phosphoric acid catalysis and chiral iridium catalysis.

Scheme 42.36 Enantioselective domino reductive amination using the Hantzsch ester as stoichiometric hydride source and catalyzed by a silylated phosphoric acid.

Domino Reductive Fragmentation/Barbier-iype AUylation... 

This Strategy based on the zinc-promoted domino reductive fragmentation/Barbier-type allylation followed by RCM has been used to prepare several carbocyclic natural products. 

The total synthesis of alkaloid (+)-lycoricidine reported by Yadav et al. represents a further application of the sequence domino reductive fragmentation/allylation followed by ring-closing metathesis in the synthesis of bioactive natural products [42], Thus, reaction of co-iodoglycoside 29 with zinc/allyl bromide in THF/HjO afforded diene 30 (87%, dr 85 15). Ring-closing metathesis of diene 30 followed by acetylation furnished cyclohexene 31. Treatment of the acetate 31 with PhINTs in the presence of Cu(acac)2, followed by sodium naphthalenide, afforded the aziridine 32 (67%), from which (-i-)-lycoricidine (33) can be easily obtained (Scheme 3.11). 

Domino Reductive Fragmentation/Barbier-Type Propargylation... 

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