JACS 1982: A Survey of Papers with a Focus on Synthetic Organic Chemistry
Baran Lab Group Meeting
15 October 2003
Carlos A. Guerrero Reagents and Methods
R1 R2 N O [H] NH OH Me N O Me R2 Me R2 R1 R1
PhNCO, H2O [H] Et3N
O O OH NH OH Me N O Me R2 Me R2 R1 R1
By 1982, the [3 + 2] cycloaddition of alkenes and nitrile N-oxides was well known. However, this chemistry had never been applied to the synthesis of b-hydroxy ketones.
The major obstacle to implementing this reaction as an aldol equivalent is over-reduction to give the b-amino alcohol.
Curran found that catalytic Rany nickel under an H2 atmosphere and addition of a buffer cleanly give imino alcohols that readily hydrolyze to give the desired compounds. Syn and anti ratios are never a problem because 1) the cycloaddition is syn and 2) the alkene geometry is fixed.
D. P. Curran. 4024. Reagents and Methods
Me2AlCl mediated heteroene reactions of aldehydes and alkenes:
Cl Me AlMe2Cl Al O O Me OH H R Me R R
The reaction of methylenecyclohexane with certain aldehydes demonstrates the utility of this reaction:
aldehyde, R Me2AlCl R = Me (91), R = i-Bu (74), R = Ph (69), R = H (80), R= t-Bu (93) OH
The moderate to high yields obtained highlight the mild nature of this transformation. Other protic or Lewis acids usually isomerize the alkene.
1, 1-disubstituted alkenes are most reactive. Ene reactions with tri- and tetrasubstituted alkenes also occur readily, but due to their slower rates, two competing reactions may take place. The first, methyl addition to the aldehyde, occurs with hindered and aromatic aldehydes. The second, aldol reaction, occurs with some aliphatic aldehydes. Alkenes which would give a secondary carbocation do not react with aldehydes other than formaldehyde.
B. B. Snider, D. J. Rodini, T. C. Kirk, R. Cordova. 555. Reagents and Methods
The Evans asymmetric alkylation reaction was discovered in 1980. The focus of his paper in 1982 was transformations of the imides that resulted after the reaction.
M O O O O O O O O R R R E O N O N O N O N E R i-Pr i-Pr E X i-Pr i-Pr
O O O O O O R R R R O N ROLi RO O N LiAlH4 RO E E E E i-Pr i-Pr
O O R BH; O O O 2 1. O3 O [O] Me 2. NaBH4 O N O O N O Me Me Me Ph Me i-Pr
D. A. Evans, M. D. Ennis, D. J. Mathre. 1737. Reagents and Methods
Davis oxaziridines: reagents that serve as chiral sources of electrophilic oxygen:
O O O2 N Ar S N H R R SO2 H Ar
R, R S, S
The oxaziridines are made in the following way:
O m-CPBA EtO OEt 2 chiral (diastereisomeric) R SO HN + R S N 2 2 oxaziridines Ar Ar
ee's for sulfide oxidations are modest (maximum of 46%). However, the reagents have been applied to asymmetric hydroxylation of enolates. In the case of a chiral enolate (Evans imide), the R group does not need to be chiral.
F. A. Davis, R. H. Jenkins Jr., S. B. Awad, O. D. Stringer, W. H. Watson, J. Galloy. 5412. Reagents and Methods
a-Lithiomethylenetriphenylphosphorane, a Highly Reactive Ylide Equivalent
Ph Ph Ph Ph Ph Ph P P
Li Li
The reagent is generated by treating methyltriphenylphosphonium bromide with 2 eq. of s-BuLi or by treating methylene- triphenylphosphorane with 1 eq. t-BuLi.
Reactivity:
Ph OLi Ph Ph PhNCO, 1st eq. PhNCO, 2nd eq. OH P PPh Ph 3 Ph Ph Li
C5H11 Ph O Ph Ph Ph Ph3P PhCHO C5H11 P C H LiO 5 11 Li HO
E. J. Corey, J. Kang. 4293. Structure Determinations
Vancomyin:
Me OH HO Me Me H2N O OH O O O Cl O O Cl HO OH O H O H O N N N NHMe O H N N H H NH O O Me HO CONH2 Me O OH HO OH
C. M. Harris, T. M. Harris. 4293. Structure Determinations
OH OH OH 1: palytoxin O O HO OH OH O OH OH O Me OH HO OH H N OH OH 2 OH OH OH HO OH O O O Me OH Me OH OH OH OH HO N N O H H H OH OH OH HO Me HO OH OH O Me O HO O Me OH Me OH OH H O OH OH OH OH HO OH "Palytoxin can now be defined as structure 1!" OH
Y. Kishi, D. Uemura, Y. Hirata, et al. 7369. Total Syntheses
CO2Me CO2Me Me 1. NaH; Tf O Me 1. LiAlH O 2 Me 4 five steps 2. LiCuMe2 2. MsCl, Et3N; LiBr geranyl bromide 81%, two steps 95%, two steps H H Me Me Me Me OMe Br MOMO HO CHO OMe Me Me n-BuLi, HMPA, TMEDA, aq. HCl Me OMOM Me OH OMe Me Me Me H MOMO Me OMe H H Me Me Me Me OMOM 75%
OMe OMe HO CHO MOMO MOMO OMe 1. MeOH, TsOH OMe 2. TBA phenoxide I 65% TBA I ; MOMCl CuCN CN Me O 3 Me O Me O Me Me Me 90%
H Me H H Me Me Me Me Me
E. J. Corey, J, Das. 5551. Total Syntheses
OMe OMe OMe MOMO MOMO MOMO OMe OMe OMe
KOH OsO4, py CN CONH2 CONH Me Me 2 O O Me O Me 92% Me 40% HO Me
HO Me H Me H H Me Me Me Me OMe OMe MOMO MOMO O aq. HCl; 0.02% TsOH, NH MeOH; TsOH, Me i-Bu2AlH; O O aq. HCl 2, 2-methoxypropane N2O4, NaOAc O Me Me O O Me O 90% Me Me Me O Me H O Me Me H Me Me MOMO CHO HO CHO
CHO CHO aq. HCl Me O Me O HO O Me Me 87% Me Me HO O H H K-76 Me Me Me Me
E. J. Corey, J, Das. 5551. Total Syntheses
OMe OMe MOMO MOMO O NH Me O O N2O4, NaOAc O Me Mechanism? Me O O Me Me O Me Me O Me H O Me Me H Me Me
O O O O N N N O O H N N N R O O N R HONO 2 2 N R N R R1 R1 2 + HNO3 2 R1 R1 O O O O NaOAc
NaNO3 + HOAc
O N O O R2 N N2 + R1 N R2 N R2 O R1 O R1 O
E. J. Corey, J, Das. 5551. Total Syntheses
O i-Pr i-Pr Me Me O OMe OH O O O O H H O O triptolide key intermediate
1. Li/NH3; isoprene; (EtO)2(O)PCl; Li, EtNH2, O O SMe O Me Me Me O t-BuOH S 2. H2SO4 CS2, LiB; MeI SMe Me Me 81% B = Me then HCl O 84%, two steps Me Me Me
t-Bu t-Bu O CO Me O O 2 Me LDA, HMPA, Me CO Me Me O OTBS 2 TBSCl OH then HCl 89% from Me Me butenolide Me
L. C. Grover, E. E. van Tamelen. 867. Total Syntheses
1. MeI, NaH CO2Me 2. MeLi i-Pr i-Pr Me 3. MsCl, Et3N Me Me 4. Li/NH m-CPBA LDA OH 3 OMe OMe 65-70% 100% 91% O Me Me Me
i-Pr i-Pr i-Pr MeO OMe Me Me 1. KOAc Me SOCl2 OMe 2. NaOMe NMe2 OMe OMe 84% 72% 80% HO Cl HO
i-Pr 1. m-CPBA i-Pr i-Pr 2. LiN(TMS) ; Me 2 Me Me aq. HCl CrO3 OMe OMe OMe 80% 25% Me2NOC O O O H H O O
L. C. Grover, E. E. van Tamelen. 867. Total Syntheses
i-Pr i-Pr Me MeO OMe Me OMe NMe2 OMe
80% Me2NOC HO
i-Pr i-Pr i-Pr Me Me Me OMe OMe OMe
OMe Me2N
Me2N O Me2N O O
L. C. Grover, E. E. van Tamelen. 867. Total Syntheses
CO Me O 2 Me CO Me Me OTBS 2 OH then HCl 89% from Me butenolide Me
HO CO2Me O CO Me O CO Me Me 2 Me 2 Me OTBS OH O
Me Me Me
L. C. Grover, E. E. van Tamelen. 867. Total Syntheses
OH steps HO O Me CO2H Ph t-BuSi 8 2 O O O Me O O TL, 1981, 2059 O O OH pseudomonic acid A key intermediate
HO CH2O, Me2AlCl OH Ac2O, py OAc CH2O, Et2AlCl OAc 72% 100% 35-40%
1. PCC, NaOAc 2. MeMgBr O 1. OsO4, NMO 3. t-BuPh2SiCl, 2. c-hexanone, Et N, DMAP Ph2t-BuSi Sit-BuPh2 3 OH O O O OAc O TsOH, CuSO4 O 4. PCC O O 82% O 52%
B. B. Snider, G. B. Phillips. 1113. Total Syntheses
N
Et N H H
dl-aspidospermidine
O O
EtO O O PhS CHO Me N NH2 N PhS
N Me 100% N Me SPh 140 C Et R R 33% N R
PhS N
R= MeOC6H4SO2 Et N R
T. Gallager, P. Magnus, J. C. Huffman. 1140. Total Syntheses
O O O O PhS PhS N N N m-CPBA TFAA; D PhS
Et 97% Et 81% Et N N N R R R
O
N N Raney Ni LiAlH4
81% Et 54% Et N N R H H
dl-aspidospermidine
R= MeOC6H4SO2
T. Gallager, P. Magnus, J. C. Huffman. 1140. Total Syntheses
Me Me albene
I (i-PrO)3P, CO2Me Pd(OAc)2 LiAlH4 O3; DMS + 63% 93% 82% CO Me CO Me HO OH TMS 2 MeO2C 2
KN(TMS)2, HMPA, O O(O)P(NMe2)2 (Me2N)2(O)PCl Li, EtNH2 54% 82% OH O(O)P(NMe ) Me HO (Me2N)2P(O)O 2 2 Me albene
B. M. Trost, P. Renaut. 6668. Total Syntheses
Me Me
O OH O Me O O Me O O B O O Me O O Me O OH O
Me Me
aplasmomycin
Me 1. LiAlH4 Me 2. actone, TsOH vinyl MgBr, CuI OsO , NMO 3. PCC Me 4 HO Me O Me O 88% Me 76% Me 70% O OH Me Me
Me Me Me3Al, Me Me propane-1,3- Me O Me Me S m-CPBA dithiol Me Me O O O O 83% O O 87% HO S OH OH Me Me Me Me
E. J. Corey, B. C. Pan, D. H. Hua, D. R. Deardorff. 6816. Total Syntheses
Me Me3Al, Me propane-1,3- O Me dithiol Me Me Me S O O O 87% HO S OH OH Me Me
O Me AlO S S Me AlS SAlMe 2 2 2 SAlMe SAlMe O O 2 O 2
Me2AlO
When the following orthoester S S was subjected to the reaction S S S S conditions, no product was formed, proving it is not O HO Me2AlO involved in the mechanism:
E. J. Corey, B. C. Pan, D. H. Hua, D. R. Deardorff. 6816. Total Syntheses
O3; DMS; propane- 1, 3-dithiol, BF3 OEt2; 2, 2- dimethoxypropane, DMSO, AcOH, Me Me Me S Me Me Me TsOH S NaOAc, Ac2O HO S 80% O S 73% OH OH O OH Me Me 1. AcOH Me Me Me 2. BzCN, Et3N Me Me Me S 3. MsCl, Et3N S 4. n-Bu OH O 4 S O S O OMTM OR Me 80% Me
O O Me OHHO Me OHC 1. MeOH, aq. HCl O Me Me Me O Me Me O TsCl, py O 2. NaIO4, NaHCO3
O O 91% O O 96% O O
Me Me Me Me Me Me
from d-mannose diacetonide and MeLi
E. J. Corey, B. C. Pan, D. H. Hua, D. R. Deardorff. 6816. Total Syntheses
Cl OHC 1. MeOH, aq. HCl O O Me Cl Me O Me 2. TIPSCl, DMAP PPh3, CBrCl3 n-BuLi 3. Tf2O, py O O O O 99%, two steps O O
Me Me Me Me Me Me
n-Bu3Sn 1. n-Bu4I 1. n-BuLi 2. NaBH4, 2. 0.5 eq. CuCN; O O Me O Me Me n-Bu3SNH, hu n-Bu3SnH, AIBN epoxide 89% bsr epoxide TfO OTIPS 56%, five steps OTIPS 75% OTIPS
1. TBSOTf, 2, 6-lut Me Me Me Me Me Me 2. AgNO3, 2, 6-lut 3. TBSOTF, 2, 6-lut. TIPSO S S TIPSO S S O OH OMTM 85% O OTBS OTBS Me Me
O OMe Me Me Me n-BuLi, TMEDA, HMPA; dimethyl oxalate O TIPSO S S 96% O OTBS OTBS Me
E. J. Corey, B. C. Pan, D. H. Hua, D. R. Deardorff. 6816. E. J. Corey, D. H. Hua, B. C. Pan, S. P. Seitz. 6818. Total Syntheses
O OMe O OH Me Me Me Me Me Me LiI, 2, 6-lut O O TIPSO S S TIPSO S S O OTBS OTBS 100% O OTBS OTBS Me Me
O OMe Me Me Me TBAF BOPCl, O Et N HO S S 3 97% O OTBS OTBS 98% Me
Me Me Me Me Me Me S S 1. LiI, 2, 6-lut S 2. TBAF S O OTBS OTBS O O OTBS OTBS O O 3. BOPCl, Et3N O O Me TIPSO Me Me Me O O 65% O O OTBS OTBS O O OTBS OTBS O S S S MeO S Me Me Me O Me Me Me
E. J. Corey, D. H. Hua, B. C. Pan, S. P. Seitz. 6818. Total Syntheses
Me Me Me Me Me S
1. NaBH4 S O OH O O OTBS OTBS O 2. 48% HF Me 3. HgCl O Me HO B(OMe) O O 2 O 3 Me OH HO Me O O O 94%, 1:1 Me 75% O OTBS OTBS O OH O S mixture of Me diastereomers O OH O S Me Me Me
Me Me
O OH O Me O O Me O O B O O Me O O Me O OH O
Me Me
aplasmomycin
E. J. Corey, D. H. Hua, B. C. Pan, S. P. Seitz. 6818.