C O MMU N I C A T I O N S
1
7
Cuprate addition using Lipshutz’s procedure and trapping of the
allylic alcohol 21 (76%). Finally, Sharpless asymmetric epoxidation
of the reagent matched allylic alcohol in 21 chemoselectively
afforded (-)-laulimalide (1, 70%).
In summary, a convergent asymmetric synthesis of (-)-lauli-
malide has been achieved in 25 steps (longest linear; 36 overall)
and in 3.5% overall yield, providing a uniquely short and efficient
route to 1 and flexible access to its analogues. Structure-activity
studies on analogues will be reported separately.
18
28
resultant enolate with Comins’ reagent afforded an enol-triflate
74%, 82% de) that upon reduction19 yielded olefin 13 (88%).
MgCl and CeCl
situ Peterson olefination generated allyl silane 2 (85%).
Conjunction of 2 and 3 (Scheme 3) with Yamamoto’s (acyloxy)-
borane 1421 gratifyingly resulted in a uniquely complex intermo-
lecular asymmetric Sakurai reaction affording 15 (86%) as the only
(
20
Treatment of 13 with excess TMSCH
2
3
and in
1
13
detectable diastereomer H and C-NMR. Protection of the C15
-
Acknowledgment. Financial Support was provided by National
Institutes of Health (CA31841). Graduate fellowship support from
Pharmacia & UpJohn, Roche Bioscience, and Eli Lilly & Co. (L.Z.)
is gratefully acknowledged.
hydroxyl as a MOM ether (99%) and chemo- and regioselective
hydroboration22 of the resultant hexaene 16 yielded upon Dess-
Martin oxidation23 aldehyde 17 (78%, 2 steps).
Scheme 3 a
Supporting Information Available: Experimental details and
analytical data for all new compounds and data for synthetic laulimalide
(1), including selected spectra (PDF). This material is available free of
charge via the Internet at http://pubs.acs.org.
References
(
1) (a) Quinoa, E.; Kakou, Y.; Crews, P. J. Org. Chem. 1988, 53, 3642. (b)
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(
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(
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(
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(
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(
8) Derived in 3 steps from the known hetero-Diels-Alder adduct of isoprene
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2
391.
9) Reagents such as Ph
photochemical conditions, failed to promote the desired conversion.
(
2 2 2
S , PhSH, and I , under various thermal and
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(
11) Greene, T. W.; Wuts, P. G. M. ProtectiVe Groups in Organic Synthesis;
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(
14) (a) Mori, K.; Kuwahara, S. Tetrahedron 1982, 38, 521. (b) Mori, K.;
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(
16) Other catalytic systems are inefficient. Use of standard Jacobsen’s hetero-
Diels-Alder conditions (-30 °C, 5.0 M) resulted in low yield (59%)
and poor diastereoselectivity (72% de), which was improved by modified
conditions (-78 to -20 °C, 3.0 M). Interestingly, the other diastereomer
of 12 can be readily accessed with use of (R,R)-Cr-Salen catalyst in
identical yield and diastereoselectivity (87%, 82% de).
a
Conditions: (a) 100 mol % 14, EtCN, -75 °C (86%, >90% de); (b)
MOMCl, DIPEA, CH2Cl2 (99%); (c) (1) BH3‚DMS, cyclohexene, THF.
(
2) H2O2, 3 M NaOH, EtOH (92%); (d) Dess-Martin periodinane, CH2Cl2,
H2O (85%); (e) MeC(dO)C(dN2)P(dO)(OMe)2, K2CO3, MeOH, 4 °C
(
80%); (f) n-BuLi, ClCO2Me, THF (75%, 86% BORSM); (g) HF‚pyridine,
THF (98%); (h) LiOH, H2O, THF (88%); (i) 2,4,6-trichlorobenzoyl chloride,
Et3N, DMAP, benzene (55%); (j) Lindlar’s catalyst, quinoline, H2, EtOAc
91%); (k) Me2BBr, Et3N, CH2Cl2, -78 °C (76%); (l) (+)-DIPT, t-BuOOH,
Ti(OiPr)4, CH2Cl2, -20 °C (70%).
(17) Behling, J. R.; Babiak, K. A.; Ng, J. S.; Campbell, A. L.; Moretti, R.;
Koerner, M.; Lipshutz, B. H. J. Am. Chem. Soc. 1988, 110, 2641.
(
(
(
(
18) Comins, D. L.; Dehghani, A. Tetrahedron Lett. 1992, 33, 6299.
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(
21) Ishihara, K.; Mouri, M.; Gao, Q.; Maruyama, T.; Furuta, K.; Yamamoto,
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Homologation of 17 under carefully controlled thermal condi-
tions, using the Bestmann modification of the Seyferth-Gilbert
reaction, followed by lithiation of the resultant alkyne and trapping
(
(
24
(24) Muller, S.; Liepold, B.; Roth, G. J.; Bestmann, H. J. Synlett 1996, 521.
with ClCO
with HF‚pyridine and subsequent saponification yielded diol acid
9 (86%, 2 steps). Macrolactonization under Yamaguchi condi-
2
Me afforded alkynoate 18 (60%, 2 steps). Desilylation
(25) Inanaga, J.; Hirata, K.; Saeki, H.; Katsuki, T.; Yamaguchi, M. Bull. Chem.
Soc. Jpn. 1979, 53, 1989.
(26) Ho, T.-L.; Liu, S. H. Synth. Commun. 1987, 17, 969, and see ref 4b.
1
(27) Guindon, Y.; Therien, M.; Girard, Y.; Yoakim, C. J. Org. Chem. 1987,
52, 1680.
25
tions proceeded exclusively at the C19-hydroxyl of the diol to give
26
(28) For an analogous epoxidation strategy on 1, see refs 4d and 4e.
macrolide 20 (55%), which upon reduction, with Lindlar’s catalyst,
yielded the Z-enoate (91%). Cleavage of the MOM ether27 afforded
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J. AM. CHEM. SOC.
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