Ricciocarpins A and

A recent application of enantioselective conjugate radical additions was seen in the synthesis of (+)-ricciocarpins A and B [95]. The key step in the synthesis was an asymmetric addition of a functionalized radical precursor 141 to afford intermediate 142 (Scheme 37). A chiral catalyst screening revealed that Mgt and bisoxazoline ligand 19 was optimal for achieving... 

Scheme 37 Application of enantioselective conjugate radical addition total synthesis of Ricciocarpin A and B...

Furanyltitanium reagents were shown to add readily to aliphatic aldehydes in the absence of any promoter, providing more desirable yields and stereoselectivity than furanyllithium, magnesium, and zinc reagents. They were employed as key steps in the total syntheses of (+)-dysidiolide <1998JOC228> and (+)-ricciocarpins A and B <20040L1749>, as depicted in Scheme 24. 

Michrowska A, List B (2009) Concise Synthesis of Ricciocarpin A and Discovery of a More Potent Analogue. Nat Chem 1 225... 

Michrowska, A., List, B. (2009). Concise synthesis of ricciocarpin A and discovery of a more potent analogue. Nature Chemistry, 1, 225-228. 

Sibi and He have described the formation of 8-lactone from an in situ formed 5-hydroxy ester in the synthesis of ricciocarpins A and B [65] (Scheme 25). Enantioselective conjugate addition of the tertiary radical derived from 133 onto... 

The difference in reactivity is perfectly revealed in Metz s total synthesis of the molluscicidal furanosesquiterpene lactones ricciocarpin A (50) and B (51) (Scheme 9) [32]. Attempts to convert acrylate 43 to lactone 44 using Grubbs5 catalyst A or Schrock s molybdenum catalyst B resulted in very low yields of the... 

Scheme 9 Comparison of substrate reactivity and catalyst activity in total synthesis of ricciocarpin A (50) and B (51) [32]...

The oxypalladation method mentioned above was introduced as a crucial step in the synthesis of several natural products. As shown in Scheme 8.51, Metz and coworkers used this strategy in an enantioselective synthesis of ricciocarpin A [122], Other impressive applications including the acetalization-RCM sequence have been employed in the synthesis of the AB ring of ciguatoxin [123] and of the Q-C fragment of laulimalide [124] (Scheme 8.52). 

An asymmetric intramolecular Michael-aldol reaction which leads to nonracemic tricyclic cyclobutanes is performed by using TMSOTf andbis[(/ )-l-phenylethyl]amine as chiral amine, but only moderate enantioselectivities are reached (eq 68). A similar reaction sequence can also be carried out with TMSOTf and HMDS as base, with (—)-8-phenylmenthol as the chiral auxiliary however, the iodotrimethylsilane-HMDS system is more efficient in terms of yield and diastereoselectivity. The combination EtsN/TMSOTf (or some other trialkylsilyl triflates) has been used to accomplish an intramolecular Michael reaction, which was the key step for the synthesis of sesquiterpene (=E)-ricciocarpin A. ... 

Scheme 7.44 Cascade conjugate hydrogen transfer/intramolecular Michael reaction and application to the total synthesis of (+ )-ricciocarpin A.

The previously discussed enamine/iminium activation cascade can also be reversed to give ricciocarpin A, as shown by List and coworkers in 2009 [8]. This interesting natural product shows some remarkable activity against a water snail species that acts as an intermediate host for the Schistosoma mansoni parasite, which is the most widespread trematode (flatworm) to infect humans and causes up to 200,000 deaths each year. 

The synthesis is initiated by the organocatalyzed cascade that activates a,p-unsaturated aldehyde 8 with the formation of an iminium ion (Scheme 14.2). In this way, the imidazolidinone catalyst allows hydride transfer from the Hantzsch dihydropyridine 9 onto the highly activated conjugated alkene 11, which creates the nucleophilic enamine intermediate 12. Because of the chirality of the organocatalyst, stereoselective Michael addition (97% ee) to the adjacent enone occurs, with minor preference for the cis diastereomer (2 1 dr). Fortunately, this undesired diastereomer slowly epimerizes to the required trans isomer, which produces (-l-)-ricciocarpin A when treated with samarium triisopropoxide. Besides the Cannizzaro-like redox disproportionation, which allows the lactone producing Evans-Tihchenko reaction to occur, samarium(III) also enhances the epimerization to the trans isomer and therefore produces the desired isomer in high selectivity. 

Audran and colleagues described two syntheses of furanosesqui-terpene natural products employing similar synthetic pathways, culminating in the use of the Barton-McCombie deoxygenation as a key step. The ester unit in bicyclic lactones 65 and 66 is used to set stereochemistry of the C-2 center. After further elaboration, the ester stereocontrol element is then reductively cleaved and cyanated to yield the diols 67 and 68, from 65 and 66, respectively. Then, in a one-pot, two-step process, activation and double deoxygenation was performed to yield reduced compounds 69 and 70, which are the intermediates in the synthesis of (-i-)-ricciocarpin A (71) and (+)-ancistrofuran (72), respectively. 

Organocatalytic C-C Ring Construction (+)-Ricciocarpin A (List) and (-)-Aromadendranediol (MacMillan)... 

Benjamin List of the Max-Planck Institut, MuUieim employed Nat. Chem. 2009,1, 225) a MacMillan catalyst for the reductive cychzation of 26. Subsequent epimerization and Tishchenko hydride transfer then proceeded with high diastereoselectivity, leading directly to the liverwort-derived (+)-Ricciocarpin A 28. 

In this very active field, Michrowska and List applied the combination of iminium-catalyzed 1,4 hydride addition and subsequent intramolecular 1,4 Michael addition for the one-pot synthesis of ricciocarpin, a molluscicidal natural product isolated from the liverwort Ricciocarpos natans (Scheme 11.29). This cascade reaction could be initiated by the single imidazolidinone (I )-3 that catalyzed both imi-nium hydride addition and Michael addition. Treatment of the Michael adduct with Sm(0/-Pr)3 induced the epimeriza-tion of the aldehyde carbon center to the more thermodynamically stable trans ring junction and subsequent Tishchenko reaction (redox process between the aldehyde... 

---