Page 1261 - Advanced Organic Chemistry Part B - Reactions & Synthesis

Scheme 13.71. Discodermolide Synthesis: I. Paterson and Co-Workers a 1237

CH 3 SECTION 13.2
CH 3
PMBO
O 2 CPh Illustrative Syntheses
O O
A
D 1) (C 6 H 11 ) 2 BCl, Et 3 N
1 ) (C 6 H 11 ) 2 BCl, Et 3 N G 2)
O CHCH 2 CH 3 OCH 2 Ph 1) (C 6 H 11 ) 2 BCl 2) CH 2 CCH O BTDMSO CH 3
Et 3 N
2) LiBH 4 CH 3 CH O
3) H 2 O 2
3) H 2 O 2
CH 3 CH 3 CH 3
TBDMSO
CH 3 CH 3 CH 3
CH 3 CH 3 O 2 CPh
PMBO
PMBO 1 7 OCH 2 Ph HO O
O OH
OH OH E 1) PMBOCCl 3
B 13 4) PhSeCH 2 CH(OC 2 H 5 ) 2
MeO O 1) SmI 2 , CH 3 CH 2 CH O H NH
1) 3) NaClO 2 2) K 2 CO 3 , CH 3 OH 5) NaIO 4 OTBDMS
MeO O 2) LiAlH 4
4) TMSCHN 2 6) CH 2 C
2) DDQ 3) Me 4 NBH(OAc) 3 OCH 3 3) NaIO 4
CH 3 CH 3 CH 3
CH 3
PMBO TBDMSO
CH O
CH 3 CH 3
O CH 3 PMBO
OCH 2 Ph
CH 3 O 2 C 1) CrCH 2 CH CHSi(C H 3 ) 3
O O O I 2) KH
+
3) H ,CH 3 OH
1) NaOMe
C 4) Dess-Martin
2) TBSOT f, lut
1) Pd, H 2 4) (CH 3 ) 2 C C(Cl)N(C H 3 ) 2 F
2) Dess- 3) KOH
Martin 5) CH 3 P(O)(OC 2 CF 3 ) 2 , 4) ArOH, DCCI,
3) NaClO 2 LiHMDS DMAP
CH 3 CH 3
8 CO 2 Ar
CH 3 O 2 C 2 PMBO 16
P(OCH 2 CF 3 ) 2
9
CH 3
O O O
O Ar 2,6-dimethyl- CH 3 CH 3
CH 3 24
CH 3 CH 3 CH 3 CH 3 phenyl 12
OTBDMS O CH
+
OPMB
O CH CH 3 J
O OPMB K
CH 3 TBDMS 1) Me SO Cl
CH 3 OTBDMS 5 2 1) LiTMP 2) LiAlH 4
2) LiAlH 4 CH 2 OH CH 3 CH 3
L 3) TBDMSOTf 17
NaH CH 3 CH 3 CH 3 4) BCl -S(CH ) PMBO CH 3 16
3 3 2 OH
CH 3 CH 3 CH 3 OPMB
CH 3 5) cat TEMPO CH 3
CH 3 O 2 C O OPMB PhI(OAc) OTBDMS
CH 3 TBDMS 2 14
O O O CH 3
OTBDMS
1) DDQ
2) Cl 3 C(O)NCO
M discodermolide
3) K-Selectride
4) HF-pyridine
a. I. Paterson, G. J. Florence, K. Gerlach, J. P. Scott, and N. Sereinig, J. Am. Chem. Soc., 123, 9535 (2001); I. Paterson,
O. Delgado, G. J. Florence, I. Lyothier, J. P. Scott, and N. Sereinig, Org. Lett., 5, 35 (2003); I. Paterson and I. Lyothier,
J. Org. Chem., 70, 5494 (2005).
The synthesis of the C(1)–C(6) subunit was based on addition of an enol boronate
to 3-benzyloxypropanal through TS-1. Immediate reduction of the chelate is also
stereoselective and provides the intermediate 13. These steps establish the configuration
at C(2)–C(5).