Synthetic possibilities Chem 315 Beauchamp 1

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1 Synthetic possibilities hem Beauchamp Propose reasonable syntheses f the following target molecules (TM-#). You can use the given starting materials and any typical ganic reagents studied in our course ( even outside our course if you know them). eaction onditions (in our course) Alkane reagents h S/E reagents (react with methyl, primary, secondary, tertiary, allylic, benzylic X patterns via S/E S/E)) a a S S a LiAl a a K a a a hydroxide alkoxides carboxylates enolates hydrogen sulfur anion alkyl sulfur anion phthalimide anion azide Alkene reagents g(ac) ( S / ). g(ac) / ( S / ). g(ac) / ab ab ab. B / z:\files\classes\\ andouts\synthesis target molecules W 0doc

2 Synthetic possibilities hem Beauchamp Alkyne reagents ( S / ) ( eq) ( eq.) g +. B-. a cat. / epoxide ( eq) ( eq.). a methyl primary X. a aldehyde ketone. a excess (zipper) wkup electrophile Alcohol reagents follow all reactions with a wkup step P S Ts-l, py.. Ts-l, py. a a. a Me o X r / pyridine P 9 0 Fischer 6 ester S. g(ac) r / ( S / ) Jones (- ) l alkene Ts- to ketone aldehyde Friedel-rafts ab eqs.of alkylation (- ) neutralize l Ts (- ) rearrangements possible Epoxides follow all reactions with a wkup step 6 7 Li 8 ( S / ) ( S / ) a/ a/ a a Li (Mg) aqueous acid acidic alcohol hydroxide alkoxide cyanide terminal acetylide enolate ganometallic S ab ab LiAl LiAl nucleophilic hydride nucleophilic deuteride nucleophilic hydride nucleophilic deuteride S Li dithiane anion Aldehyde reagents follow all reactions with a wkup step Li eqs S Li Ts (- ) Ts (- ) a a (Mg) Ph P make ketals make ketals slow addition of acid S Li Wittig reaction enolates & acetals & acetals make cyanohydrins terminal acetylides ganometallic dithiane anion makes alkenes aldol reactions 9 0 Li 6 r /. LA, -78 o Jones mpba p Zn / l a p X oxidize to oxidize to (- ) (- ) LA, -78 o carboxylic acids carboxylic acids make imines make enamines lemmenson reaction Wolff-Kishner rxn make enolates react enolates z:\files\classes\\ andouts\synthesis target molecules W 0doc

3 Synthetic possibilities hem Beauchamp Ketone reagents follow all reactions with a wkup step Acid reagents Pb(Ac) /Li P (- ) Kochi reaction makes - Friedel-rafts acylation Acid chlide reagents Amides Anhydrides Amines z:\files\classes\\ andouts\synthesis target molecules W 0doc

4 Synthetic possibilities hem Beauchamp Ethers itriles Alpha-beta unsaturated carbonyl compounds,-dicarbonyl compounds Aromatic chemistry Template z:\files\classes\\ andouts\synthesis target molecules W 0doc

5 Synthetic possibilities hem Beauchamp epresentative X patterns from - 7: (), (), (), (), (8), 6 (7) and (9) examples, not counting stereoisomers such as enantiomers and diastereomers - in our course, many of these can be made from: a. free radical substitution, b. alcohols c. alkenes. You have to know the limitations (our rules) of S / E chemistry (strong vs weak), (me basic vs less basic), substitution patterns, substitution patterns, etc z:\files\classes\\ andouts\synthesis target molecules W 0doc

6 Synthetic possibilities hem Beauchamp 6 epresentative patterns from - 7: (), (), (), (), (8), 6 (7) and (9) examples, not counting stereoisomers such as enantiomers and diastereomers - many of these can be made from: a. X compounds, b. alkenes c. carbonyl compounds d. epoxides z:\files\classes\\ andouts\synthesis target molecules W 0doc

7 Synthetic possibilities hem Beauchamp 7 epresentative alkene patterns from - many of these can be made from: a. X compounds, b. c. Wittig reaction (= compounds) d. alkynes z:\files\classes\\ andouts\synthesis target molecules W 0doc

8 Synthetic possibilities hem Beauchamp 8 epresentative aldehyde and ketone patterns from - many of these can be made from a. alcohols, b. alkynes c. nitriles d. esters e. acid chlides f. carboxylic acids g. alkenes h. other reactions we don't know. The aldehydes can be made into caroboxylic acids, alcohols and alkenes, imines, enamines, enolates, enol ethers, acetals and me. Acids can be made into esters, acid chlides (many possibilities), alcohols, ketones and me. Ketones can be made into alcohols, alkenes, esters, enol ethers, enolates, enamines, imines and me z:\files\classes\\ andouts\synthesis target molecules W 0doc

9 Synthetic possibilities hem Beauchamp 9 z:\files\classes\\ andouts\synthesis target molecules W 0doc epresentative acid patterns from -manyofthesecanbemadefroma. o, b. alkenes ( )c

10 Synthetic possibilities hem Beauchamp 0 z:\files\classes\\ andouts\synthesis target molecules W 0doc epresentative amide patterns ( o, o, o, = from - can be made from a. acid chlide +,ammonia a o o amine b. nitriles can make o amides 8 9 0

11 Synthetic possibilities hem Beauchamp z:\files\classes\\ andouts\synthesis target molecules W 0doc

12 Synthetic possibilities hem Beauchamp epresentative patterns ( = ) from - 7 skeletons: (), (), (), (), (8), 6 (7) and (9) examples, not counting stereoisomers such as enantiomers and diastereomers - many of these can be made from: a. X compounds and. phthalimidate b. a. a LiAl. wkup c. nitrile + LiAl wkup d. aldehydes ketones +, (-) a B. wkup itter rxn problem itter rxn f us problem f us itter rxn itter rxn 9 0 problem f us itter rxn itter rxn itter rxn problem f us itt er rxn problem f us itter rxn z:\files\classes\\ andouts\synthesis target molecules W 0doc

13 Synthetic possibilities hem Beauchamp The following are useful transfmations using the given alkane starting points. eagents are not given over the arrows, but possibilities are suggested below each list by number. h P S a. Tsl/py b. a S Li (Mg) a S.. a Li Mg Al LiAl metal a metal (aromatic chem) a a a a a a r /py r / X (P) (Jones) (S ). a X (S ) l Ts (- ) Fischer ester syn LiAl. ab P(Ph) r /. Li (Mg) p = (Jones) Wittig rxn (- ) imines a a l = unstable. a X (S ) only. LiAl Sl (but no good f acid). eqs. Li Assume all reactions finish with a wkup step. Assume all reactions finish with a wkup step. S Li (Mg) h. a (S ) (S ) a a S.. a Li Mg metal metal LiAl a a a a K Al (aromatic chem) Ts 6 P S a. Tsl/py b. a r /py (P). a r / X (Jones) X (=Me, o (= o, o X, S ) X, S ) a S / (E rxns) 6 Ts-l pyridine z:\files\classes\\ andouts\synthesis target molecules W 0doc

14 Synthetic possibilities hem Beauchamp 6 7. LiAl. ab P(Ph) Wittig rxn mpba p = (- ) imines.. Li (Mg) 6 a a 7 z:\files\classes\\ andouts\synthesis target molecules W 0doc

15 Synthetic possibilities hem Beauchamp eaction Wksheet Possible Approaches. a + equivalents. a +. K + h available. a + equivalents. a +. K + h available a / Pd / quinoline (Lindlar's cat.) Pd / quinoline (Lindlar's cat.) Use any of these. Pd / 6 LiAl Use either of these. 6 S / S 7 Pd / / SS 7 Pd / a h 8 available 9. B / 9 r pyridine 9., -78 o S has to be made 0 + / (g + cat.) Either of these. 0 r / pyridine r / 0., -78 o S has to be made. B / a + + /. g(ac) / ab Any of these..lial ( ab ) Any of these.. a z:\files\classes\\ andouts\synthesis target molecules W 0doc

16 Synthetic possibilities hem Beauchamp 6. B / P. Ts-l, py. a Any of these. h 6. B / ( is prepared in 8) a 8,9,0,. B The other ethers / are prepared in a similar way using S and S reactions. f 8 f a f. B / 8 f. a. a r / 9,6,7,8,9,0 (similar). a. a (from ) a a a h available. a. a 6 is similar 6 6 is similar. B / available h.k + ( ) a mpba mpba mpba. /. / a a. / a z:\files\classes\\ andouts\synthesis target molecules W 0doc

17 Synthetic possibilities hem Beauchamp 7 0. a + / / 7 7. a 7. a 7 (from ) Ts. a 7 7 / / S 8 and S. a / / / / / / / / and SS a 8 S 0 and S a 9 + / / + / 8 / 9 / / 6 /. a 8. a /. a a 9 7 and 8 are similar with mpba. / a z:\files\classes\\ andouts\synthesis target molecules W 0doc

18 Synthetic possibilities hem Beauchamp 8. a 9. a 9 (from ) a 6. a 6. a 0 6. a 6. Li+ = (LA) Li+ = (LA) 9. Li+ = (LA). Li+ = (LA) Li+ = (LA) 70. Li+ = (LA). Li+ = (LA). Li+ = (LA) S (also S).LiAl 7.LiAl.LiAl 7 ( ab ) ( ab ) (also SS) ( ab ) 8 7.LiAl ( ab ) 9.LiAl 76 7 ( ab ) 77.LiAl ( ab ) 9 78.LiAl ( ab ) 0. Li+ = (LA) Li+ = (LA) 8. Li+ = (LA) 8., -78 o S., -78 o ab 8 8., -78 o / 8 z:\files\classes\\ andouts\synthesis target molecules W 0doc

19 Synthetic possibilities hem Beauchamp 9. B / + / (g + cat.) r / pyridine r / r pyridine., -78 o S a + + /. B /. B / of P. Ts-l, py. a. a.lial. a. a. B /. B /. a (from ). a r / a h / + / / Ts. a. a 7., -78 o /., -78 o ab equivalents + / /.LiAl ( ab ) mpba. / a similar to 0. a 9 ( ab ). g(ac) / ab. Li+ = (LA) z:\files\classes\\ andouts\synthesis target molecules W 0doc