C-O C-O C-N A A. (KHMDS) C-N (scheme 1) C-O C-N (1)

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1 C- C- C- A A t- (Boc)-- (MM)- () (KMDS) C- (scheme ) C- C-

2 () C- C- C- C- C- C- B C- B (scheme 2) C- B (2) C- manzacidin A Manzacidine A (5) - ATP (fig. ) C- 5 Ph MM Boc ethyl lactate X n=,2 n M + B Et K X n Et M B (fig. ) 5: Manzacidin A C 2 n * 4 (Scheme 2) () C- C- A MM C2 tbu E-X Ph E MM Boc 2 (Scheme ) C- (2) C- manzacidin A (scheme ) C- 8 9 L-Ala L-Ser () C- (scheme 4) 0 2TBS 7 4 esterification C 2 (scheme ) TBS a, b, c TBS d e, f 0 2 Scheme 4. a) (C 2 )n, MgCl 2, C, reflux; b) ab 4,, 0 C; c) TBSCl, imidazole, C 2 Cl 2, 0 C~rt; d) DAD, L-ethyl lactate, PPh, TF, rt; e) F pyr., pyridine, TF, rt; f) BS, PPh, C 2 Cl 2 C a b c, d, e Scheme 5. a) Ph PC 2 Cl, t BuK, TF, rt; b) DAD, L-ethyl lactate, PPh, TF, rt; c) CuCl 2 (cat.), 2, C, reflux; d) ab 4, Et, 0 C; e) 2, PPh, imidazole, Ph, rt. 7 P C 2 C 2 mory of Chirality amds TF, 78 C Boc 8 MM C 2 Et 9 Cbz 8 (scheme ) 9: 0% ee L-Ala L-Ser

3 8 C- C- Table. 5-membered cyclization reactions amds C TF 2 Et * 78 C entry starting material product yield (%) ee (%) (S) 2 i Pr (S) TMS (S) 4 Ph C(scheme ) C- C() (table )20 (amds) 78 C 2% 84% ee(entry )2 CD S 22 (entry 2) C()C- TMS C() 25, 29 (entry, 5) 27 (entry 4) C()TMS 2S)-ethyl 2-hydroxybutanoate 0 TMS )amds TF, 78 C 2) TFA TMS 0 ) Li 2 TF// 2 (scheme 7) efaroxan (scheme 7) C() (entry ) 7b C(), 4 (entries 2 and ) 8a, 9a C() 5 Table 2. -membered cyclization reactions base (2 eq.) TF 78 C * 2 2 C2 Et 2 2,, 4, 5, 7a, 8a, 9a, 7b, 8b, 9b, 40a, 4a 40b, 4b entry starting 2 material base products (yield, ee) 2 amds 7a (27%, 0%), 7b (9%) a) 2 KMDS 8a (40%, 0%), 8b (24%) a) i Pr 4 KMDS 9a (7%, 0%), 9b (54%) a) 4 5 LDA 40a (77%, 4%) 5 5 amds 40a (5%, 52%), 40b (%) a) 5 KMDS 40a (7%, 0%), 40b (27%) a) 7 i Pr LDA 4a (88%, 74%) 8 i Pr TMS( t Bu)Li 4a (%, 84%), 4b (trace) a) The ees were not determined. LDATF 78 C 40a7% 4% ee(entry 4) (entries 5, ) C() LDA88% 74% ee LDATMS( t Bu)Li Scheme 8. Butressing Effect Li Et TMS( t Bu)Li i Pr Pr i Pr i C2 Et 4a (%, 84% ee) Electrophilic center is close to the enolate i Pr 4 84% ee 4a (entries 7 vs 8)C() buttressing 4a KMDS i Pr K Et Pr i C2 Et 9a (7%, 0% ee) Electrophilic center is far from the enolate (Fig. 2) esult of PGME method Ph C = (S) ()

4 ()(S)phenylglycine methyl ester (PGME)PGME (S) () (figure 2) Scheme 9. Synthesis of ()-trolox (42) LDA (2.0 eq.) MPA (5.0 eq.) TF, 78 C 4%, 0% ee C2 Et 4 44 ()-trolox (42) (scheme 9) 2,,5-trimethylhydroquinone 4TF 78 CMPALDA C-B C (figure )22 TBS 4 Pr i Et Et 45 M G 2 =.5 kcal/mol Li 2 TF// 2 C2 42 (fig. ) ) amds TF, 78 C 2) TBSTf t /2 = < ~ sec ( 78 C) (scheme 0) 47 48TF 78 C amdstbstf47 (scheme 0)47 ESYZ 47M 47C-.5 kcal/mol4 C-4 78 C C- Et 4 TBS C- (2) C- manzacidin A L-Ala 8 47 L-Ala Boc MM C a, b, c 2 Et L-Ala MM 8: =Boc 47: =Cbz Scheme. a) SCl 2, Et, reflux; b) Boc 2, ac, 2 or CbzCl, ac, 2 ; c) TMSCl, (C 2 )n, C 2 Cl 2 then 8 47 Cbz MM (scheme ) 48 Ms 48 (fig. 4) C 2 Tr L-Ser - (figure 4) Axially Chiral Binaphthyl Surrogates with an nner -- ydrogen Bond. Kawabata, T.; Jiang, C.; ayashi, K.; Tsubaki, K.; Yoshimura, T.; Majumdar, S.; Sasamori, T.; Tokitoh,. J. Am. Chem. Soc. 2009,, Total Synthesis of (+)-Sundiversifolide. Yokoe,.; Sasaki,.; Yoshimura, T.; Shindo, M.; Yoshida, K. Shishido, K. rg. Lett. 2007, 9, C C C- 27

5 C T. Yoshimura, K. Tomohara, T. Kawabata; Asymmetric Synthesis via Planar Chiral Enolates ; Third nternational Conference on Advanced rganic Synthesis Directed toward the Ultimate Efficiency and Practicability (Shiga, 27 th May 2008, Japan) T. Yoshimura, K. Tomohara, T. Kawabata; Asymmetric Synthesis of dihydrobenzofurans and chromans via planar chiral enolates ; First nternational Symposium on Process Chemistry [SPC08] (Kyoto, 0 th July 2008, Japan)

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