Crimmins synthesis

Finally, a radical cyclization/oxidation protocol was utilized as the final step in the Crimmins synthesis of the natural product (-)-talaromycin A.41 Silylation of allylic alcohol 42 produced 43, which cyclized upon treatment with BusSnH and AIBN to provide 44. Oxidation of the crude residue resulting from the cyclization reaction resulted in the formation of (-)-talaromycin A (45). 

M. T. Crimmins, W. G. HoUis, Jr., and R. O Mahony, iu Atta-ur-Rahman, ed.. Studies Directed Toward the Total Synthesis of the Milbemjcins and... 

A year after the total synthesis of (+)-laurencin [85], Crimmins disclosed the total syntheses of (+)-prelaureatin (169) and (+)-laurallene (168) by applying a similar strategy (Scheme 31) [86]. The critical RCM reaction was undertaken... 

Scheme 32 RCM-based synthesis of the A5-oxonene 171 in Crimmins total synthesis of iso-laurallene (172) [87]...

Scheme 33 RCM-based total synthesis of the marine cyclic ethers obtusenyne (177) [88] and rogioloxepane (180) [89] by Crimmins and coworkers...

For the previous preparation of a mixed acrolein acetal and its use in an RCM reaction during callystatin A total synthesis, see Crimmins MT, King BW (1998) J Am Chem Soc 120 9084... 

In several cases of syntheses of highly functionalized molecules, use of CH3Li-LiBr for ylide formation has been found to be advantageous. For example, in the synthesis of milbemycin D, Crimmins and co-workers obtained an 84% yield with 10 1 Z E selectivity.251 In this case, the more stable E-isomer was required and it was obtained by I2-catalyzed isomerization. 

A bromoallene 75 was prepared from 74 following the standard procedure and used in the natural product synthesis [31] of 78 (Scheme 4.19) [32]. Crimmins and Emmitte succeeded in the construction of the chiral bromoallene moiety of isolaur-allene 83 by bromination of propargyl sulfonate 81 with LiCuBr2 as a key step (Scheme 4.20) [33] (cf. Section 18.2.3). 

In their total synthesis of isolaurallene (66), Crimmins and co-workers [85] relied on the anti-selective S -substitution of a propargylic sulfonate with LiCuBr2 (cf. Schemes 18.21 and 18.22) instead of the enyne cyclization sequence, which had turned out to be unsatisfactory in terms of stereocontrol (Scheme 18.26). 

Crimmins MT, Al-awar RS, Vallin IM, Hollis WGJ, O Mahony R, Lever JG, Bankaitis-Davis DM (1996) J Am Chem Soc 118 7513 Mitsunobu 0 (1981) Synthesis 1... 

Crimmins reported the synthesis of enantiomerically pure cyclopentenol derivative 8 from diene 6 using ring-closing olefin metathesis followed by treatment with UBH4 [Eq. (6.7)] ... 

Furstner succeeded in the synthesis of dactylol using ring-closing metathesis of 9d. Crimmins synthesized enantioselectively diene 9e, and RCM of 9e gave eight-membered ring compound lOe, which is an intermediate for the synthesis of laurencin [Eq. (6.12)] ... 

There are times that it is important to run the Grubbs reaction under equilibrating conditions. In the course of a synthesis of ophirin 12, Michael Crimmins of the University of North Carolina observed (J. Am. Chem. Soc. 2004,126, 10264) that metathesis of 8 under the usual conditions gave mainly the undesired cyclic dimer. At elevated temperature, the dimer re-entered the equilibrium, leading to the desired 9 as the major (15 1) product. The oxonene ring system of 10 then directed the intramolecular Diels-Alder cycloaddition, leading to 12. 

Another example is Crimmins and Gould s114 total synthesis of ( )-laurenene 243 via the intramolecular photoaddition of enone 241, affording an epimeric mixture with very high facial selectivity, followed by subsequent transformations (Scheme 52). 

The effect of substituents at the a-carbon of the enone on the stereoselectivity was examined on compounds 270, with the stereogenic center located at the alkenyl side chain. Crimmins and DeLoach122 found that the stereoselectivity encountered upon irradiation of 270 depends on the degree of steric hindrance associated with the ester group linked to the double bond. The ratio of the two epimeric centers at the C-9 position varied from 13 1 (R = Me) to 17 1 (R = Et), then 20 1 (R = i-Pr). These results demonstrate that steric effects play an important role in controlling the stereofacial selectivity in these and related systems. Fragmentation of the photoproduced four-membered ring and simple transformations afforded synthesis of ( )-pentalene 274, (i)-pentalenic acid 275 and (i)-deoxypentalenic acid 276 (Scheme 59). 

Crimmins MT, Emmitte KA (1999) Total Synthesis of (+)-Laurencin An Asymmetric Alkylation-Ring-Closing Metathesis Approach to Medium Ring Ethers. Org Lett I 2029... 

Crimmins MT, DeBaillie AC (2003) Enantioselective Total Synthesis of (+)-Rogioloxe-pane A. Org Lett 5 3009... 

Removal of the tri-wo-propylsilyl (TIPS) and tm-butyldimethylsilyl (TBS) protecting groups could be accomplished concomitantly with TBAF in tetrahydrofuran at 0 °C, but here competing elimination of the secondary bromide was observed. Better overall yields and cleaner conversion was observed when TBS ether was cleaved with 5 % aqueous HF in acetonitrile at 0 °C followed by removal of the acetylenic TIPS with TBAF under milder conditions of -78 °C.10 The diastereomers are not separated before the desilylation process therefore even a 3 1 mixture of E- and Z-enyne is obtained. Prelaureatin 4 and its F-isomer 17 are likewise goals in natural product synthesis. Crimmins and co-workers developed an own synthetic route to 4. The reaction sequence is similar up to aldehyde 55. Afterwards a Z-vinyl-iodide is selectively formed and the alkyne is introduced via a Sonogashira reaction. 

Crimmins, M. T. Tabet, E. A. Formal total synthesis of (+)-trehazolin. Application of an asymmetric aldol-olefin metathesis approach to the synthesis of functionalized cyclopen-tenes./. Org. Chem. 2001, 66, 4012-4018. 

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