Pattenden’s synthesis

Scheme 11. Intramolecular free radical conjugate addition in Pattenden s synthesis of alliacolide (61).

Pattenden s synthesis of (/ )- and (S )-2-methyl-cysteine [12] is based on Seebach s self regeneration of chirality [13]. Scheme 5 shows the synthesis of the (/ )-isomer 5b. 

Scheme 5. Pattenden s synthesis of the (/ )- and (S)-2-methylcysteine building blocks.

There are many synthetic examples that use radical cyclization as a key step, and the radical precursor is not limited to iodides or bromides. In Pattenden s synthesis of pentalenene, conjugated selenyl ester 156 was treated with Bu3SnH and AIBN to give a 45% yield of tricyclic ketone 159. Loss of PhSe generated the acyl radical 157, which exists in equilibrium with the ketene radical 156. Radical cyclization via the latter intermediate leads to 159. Cyclization via aryl radicals is also possible. In Schultz s synthesis of hexahydro-phenanthren-2-one derivatives, " aryl bromide 160 was cyclized to 161 in 78% yield under standard conditions. Radical cascade reactions have become quite popular for the synthesis of polycyclic ring systems. In these reaction, polyenes are subjected to radical cyclization, generating tricyclic or even tetracyclic ring systems. 5 Chiral auxiliaries have been used effectively in radical cyclization reactions. ... 

In nearly two decades, challenging structured of phomactins coupled with the interesting biological activity has elicited an impressive amount of synthetic efforts [16-18]. (+)-Phomactin D was first synthesized by Yamada in 1996 [19], and Wulff [20] reported the synthesis of ( )-phomactin B2 in 2007. However, (+)-phomactin A has been the most popular target because of its unique topology. To date, two monumental total syntheses have been accomplished Pattenden s [21] racemic synthesis and Halcomb s [22] asymmetric synthesis in 2002 and 2003, respectively. Both syntheses are beautifully done but also mimicked Yamada s synthesis of D, thereby underscoring the remarkable influence of Yamada s earlier work on the phomactin chemistry. Upon completing their synthesis of ( )-phomactin A, Pattenden [23] completed ( )-phomactin G via a modified route used for A. 

Stille couplings also have been exploited in the synthesis of the aromatic macrocyclic core of diazonamide A (2) [5, 20]. Pattenden s group utilized the Pd-catalyzed coupling between the 3-stannyl substituted indole 23 and the 3-bromooxazole 24 to provide a particularly expeditious route to the ring system 25 [20]. In addition, Harran s group secured the connection between bromooxazole 12 and vinylstannane 26 also using a Stille coupling [5]. 

The first total synthesis of a racemic dolastane (rac-llO) was apparently published by Pattenden as a short communication 1986 followed in 1988 by a full paper [77, 78]. Pattenden s strategy is based on an intramolecular [2+2]-photocycloaddition/cyclobutane fragmentation to transform the diene 133 into the hydroazulene 136 (Scheme 20). In between the cycloaddition... 

The enantioselective ex-chiral-pool synthesis of the enantiomer of the natural (-i-)-dolasta-l(15),7,9-trien-14-ol (ent-122) was achieved by Mehta and coworkers in 1987 (Scheme 24) [85, 86]. From the hydroazulene 136, the synthesis proceeded analogous to the synthesis of Pattenden (Scheme 20) and provided the dolastane ent-122 as a mixture with the non-natural dolas-tanes 153 and 154. However, in contrast to Pattenden s work, Mehta and... 

A similar coupling of 4 and 5 was applied for the synthesis of the macrolide anti-tumor agent rhi-zoxin D (7) by White and coworkers (Scheme 5.4.2).2S Pattenden s group also accomplished the total... 

Pattenden s group " " completed and described the total synthesis of 1195. In their early work, the phosphonium salt 1543 was elaborated sequentially to the ( , )-diene 1566 (Scheme 1.398). 

In 1975, Pattenden etal. reported the first regiospecific synthesis of permethylated pulvinic acids 46 [48] and pulvinones 45 [49] by condensation of 44 with aroyl formates and aryl aldehydes, respectively, followed by dehydration (Scheme 1.5). Interestingly, Pattenden s pioneering work allowed the first total synthesis of naturally occurring pulvinones, first isolated from natural sources in 1973 [3b] but... 

In 2006, be Gall et al. [67] presented a conceptually different approach for the synthesis of pulvinic acids, starting from commercial tetronic acid 87 (Scheme 1.12). The protocol involves application of Pattenden s arylidenylation by aroyl formates, iodination, and aryl coupling by Suzuki reaction. The utility of be Gall s method was exemplified by the synthesis of vulpinic (24) and pinastric (26) acid. 

G. Pattenden, Royal Society of Chemistry, London, 1978, vol. 1, pp. 197-287. Synthesis of Multidentate Compounds , J. S. Bradshaw, in Synthetic Multidentate Macrocyclic Compounds , ed. R. M. Izatt and J. J. Christensen, Academic Press, New York, 1978, pp. 53-109. 

S. Handa, G. Pattenden, Free Radical-Mediated Macrocyclizations and Transannular Cyclizations in Synthesis, Contemp. Org. Synth. 1997, 4, 196-215. 

Fukuyama [5] obtains the building blocks by an enzymatic ester hydrolysis (6 7). As both enantiomers are needed in the synthesis, Ehrler [6] uses the separation of a racemate by chromatography of 8. A stereoselective alkylation is the key step in the work of Pattenden [7] (9 10), Heathcock [8] (11 12) and Kiso [10] (13 14). Wipf [9] starts from (S)-methylserine... 

For the synthesis of Thiangazole, Pattenden and co-workers prepared the oxa-zole derivative 25.3 [Scheme 5.25] from the a-methyl cysteine derivative 25.1 in four steps.55 The final step in the sequence involved acidolytic cleavage of both the N-Boc and S-Boc protecting groups with anhydrous HC1 in ether. However, in certain circumstances, an N-Boc group can be cleaved in the presence of an S-Boc group and a /erf-butyl ester [Scheme 5.26).56... 

Transannulation of the mesylate (33), derived from 4,8-dimethylcycloocta-4-en-l-ol, using sodium carbonate in aqueous dioxane has provided the bicyclo[3.3.0]octanol (34), a central precursor to the monoterpene iridomyrmecin (35 equation 13). In studies of the biomimetic synthesis of the natural tri-quinanes capnellene (37 equation 14) and pentalenene (40 equation IS) Pattenden et al. have shown that both molecules can be produced from appropriate cycloocta-l,S-diene precursors, i.e. (36) and (39) [or indeed their corresponding positional isomers (38) and (41), respectively] by treatment with boron trifluoride. Mehta et al. have described an alternative transannulation approach to the triquinane unit found in pentalenene, i.e. (42) - (43 equation 16), and also to the ring system (44 equation 17) found... 

Chattopadhyay, S.K., and Pattenden, G., Towards a total synthesis of ulapualide A. A concise synthesis of the fm-oxazole macrolide core and entire carbon skeleton, Synlett, 1345, 1997. 

Poss, M.A., and Reid, J.A., Synthesis of the hydroxyethylene dipeptide isostere, (2S,4S,5S)-5-amino-6-cyclohexy]-4-hydroxy-2-isopropyl hexanoic acid n-butyl amide. Tetrahedron Lett., 33, 1411, 1992. Handa, S., Pattenden, G., and Li, W.-S., A new approach to steroid ring construction based on a novel radical cascade sequence, J. Chem. Soc., Chem. Commun., 311, 1998. 

Zhang, J., and Xu, X., Total synthesis of 6-ep/-sarsolilide A, Tetrahedron Lett., 41, 941, 2000. Boehm, H.M.. I landa, S., Pattenden, G., Roberts. L.. Blake, A.J., and Li, W.-S., Cascade radical cyclizations leading lo steroid ring constructions. Regio- and stereo-chemical studies using ester- and fluoroalkene substituted polyene acyl radical intermediates.,/. Chem. Soc., Perkin Trans. 1, 3522, 2000. Hampton, A.. Sasaki, T, and Paul, B., Synthesis of 6 -cyano-6 -deoxyhomoadenosine-6 -phosphonic acid and its phosphoryl and pyrophosphoryl anhydrides and studies of their interactions with adenine nucleotide utilizing enzymes, J. Am. Chem. Soc.. 95. 4404, 1973. 

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