EXAM%2!RANGE!OF!SCORES!=!4-119!(47%!earned!>!60%,!which!is!“B-“!and!above)!MEAN!(AVERAGE)!=!56.0%!(“low!C+”)!and!MEDIAN!(score!#172)!also!=!56%!DISTRIBUTION!FOR!FALL!2019!(344!scores)!%%%EXAM%1!RANGE!OF!SCORES!=!0-120!(72%!earned!>!60%,!which!is!“B-“!and!above)!MEAN!(AVERAGE)!=!67.5%!(“mid!B”)!and!MED IAN !(score!#18 5)!=!74% !(high“B ”) !DISTRIBUTION!FOR!FALL!2019!(369!scores)!!!!!Regrade%request%-%https://www.surveymonkey.com/r/F19215E2R%!!!I (26 points)Name _________________________________________Complete the following reaction sequences as required.26/06c/08b(a) Tetrahedron Lett. 1993, 34, 7509CH3O1)H3COOOCH3ONaH,2) work-up to neutralizeH2NOHethanolNOOCH3O1) LiAlH42) H3O+ protonation1) PBr32) NaN3(b) Tetrahedron Lett. 1995, 36, 5187CPh3NNNNHOHOHCPh3HCPh3NNNNHHHCPh3H1)2)CPh3NNNNHCPh3HH3COOCH3(c) Tetrahedron 1992, 48, 9495/12aOOOOOH3CONLi21)2)HOOCH33) work-updraw the enol form of the product that includes an intramolecular hydrogen bond, and show it with a dashed line644444O OOOCH3NOOHNON3LiAlH4work-up,neutralization,etc.H3CClOoranhydride,or ester(CH3CH2)3N orNOOOOOH3COOHno partial, but either enol form OKC11H10O4no partialno partialC10H9NO2C10H8N4O2 pts, “excess”OK not req.2 pts only ifLiAlH4 correct2 pts, writing 2 equiv or “excess”OK but not req.2 pts only ifOK acylatingagent is used,no credit for only the added baseOH3COOHReither of theseare OK = 4 pts;2/4 if ald/esteris shown;if OK, +2 forthe rest2-stepalternative:1) NaH2) the acylating agent, as aboveOH3COORHII (28 points)Name _________________________________________28/02e/06d“b-Lactams are the crucial structural skeletons of important and widely applied b-lactam antibiotics [e.g., penicillins, cephalosporins] and key intermediates in organic and pharmaceutical synthetic chemistry as well.” (Jiaxi Xu, Tetrahedron 2012, 68, 10696). In one of the standard methods to prepare b-lactams, the enolate adds to an imine and the resulting nitrogen anion undergoes an intramolecular acylation. Provide the complete, step-wise mechanism for the following example of this method./06c/06bO OO1) NaH2)PhNTsHOONTsHPh(a) formation of the enolate (draw the complete reaction: starting materials to products)(b) reaction of the enolate with the imine (draw the complete reaction: starting materials to products)(c) intramolecular acylation reaction (draw the complete reaction leading to the products)(d) What is the IUPAC name for this starting material?O OOCH3a b-lactamCH3(e) How many stereoisomers are possible for the b-lactam, whose connectivity is pictured above?/08a26866O OOCH3HHHNaO OOCH3HNa+ H2• starting materials & mech (2 or 3 arrows) = 3 pts• product: C- or other enolate res contributor = 3 pts• + H2 = 2 ptsO OOCH3HNaPhNTsHOONTsHPhOCH3Na• starting materials & mech (2 or 3 arrows) = 3 pts• product = 3 ptsOONTsHPhOCH3NaOONTsHPhOCH3NaOONTsHPhOCH3Na• starting material & 2 arrow mech = 2 pts • intermediate = 2 pts• 2 arrow mech = 2 ptsmethyl 3-oxobutanoate or methyl 3-oxo-1-butanoate or methyl 3-oxobutan-1-oate-2 per class of error (punctuation, space, methyl, prefix, root, suffix, numbers)4Ts =SOOCH3reminder:III (26 points)Name _________________________________________/08B/06AcThe following reactions are proposed to occur through a sequence of steps. In each case, a description of the steps is provided, an inventory of the functional groups, and the molecular formula of the product. Based on this information, draw the structure of the product. Double check your structures against the molecular formula and the descriptions!26(a) Comprehensive Organic Synthesis, 1991OOOH3COH3COOCH3CH3ONaCH3OHOPhC19H22O7deprotonation of an acidic a-H produces an enolate that undergoes an intermolecular conjugate addition reaction; the resulting enolate intermediate then undergoes an intramolecular conjugate addition reaction; simple protonation then gives the observed product, which contains 3 esters and a ketone6(b) Comprehensive Organic Synthesis, 1991C14H20O4the 2˚ alcohol is acylated by the b-lactone; when the b-lactone opens, it releases a enol that tautomerizes (equilibrates) into its keto form, giving the observed product, which contains a ketone, an ester, and a conjugated (a,b-unsaturated) aldehyde6(c) JACS 2002, 124, 4642C16H22N2O4Sthe thioester acts as an acylating agent, with the thiol nucleophile, to give another thioester; the new thioester undergoes an intramolecular acylation with the 1˚ amine to give an amide, releasing the thiol back to its original form, in the observed product, which contains 2 amides, an ester, and a thiol6OOHOOHb-lactoneHSNH2NOCH3OOCH3PhCH3SO+A.Draw: (2E, 4S)-N,N-diethyl-4-mercaptohex-2-enamideB.8/06Ab/06AaOOH3COH3COPhOOOCH3HOOOOHSNHNOCH3OOCH3PhOCH3NOHSHkey component (bold) = 2/6otherwise no partialkey component (bold) = 2/6otherwise no partialkey component (bold) = 2/6otherwise no partial-2 per error6C amide, E-C=C, S-thiol,position of groups, ethylsacidcatalystmildlybasicconditionsIV. (25 points)Name _________________________________________Complete the following reactions as required. Use structures for reagents (not acronyms).(a) a novel “double-Weinreb” reagent (JOC 1991, 56, 2911)NCH3CH3NOOCH3H3CO1)2) H3O+SH3CLilow temperaturelow temperature3)4) H3O+CH3CH2CH2CH2Li(b) Tetrahedron 2009, 65, 4212H3COOOOCH31)H3CO CF3O2)NaH1 equivalent3) H2O/H2SO4hydrolysis &decarboxylationC10H14OSC5H5F3O3(c) Tetrahedron 2009, 65, 10863O1) 2) 3)OOHOCH2Ph(d) ACS Med Chem Lett 2019, 10, 534BrOCH3BrFONOCH3BrFOH80˚C+ CH3OHcatalytic(CH3CH2)3N/06d/09c25/05b/05a553333 3SH3CCH2CH2CH2CH3OHOOOCF3Cu2LiOOCH2PhHH3O+HNHin excess orplus an added3˚ base (R3N) orpyridineNBrFOno partial2/5 for the enol on the CF3 endno partialno partialno partialcan be lithium orGrignard reag + CuIcan be “H2O” or “work-up” or “protonation”2 pts for cyclohexyl amine1 pts for excess or additionalbase (but only if amine is OK)no partialV. (15 points)Name _________________________________________15/03c/10bProvide the complete, step-wise mechanism for the following intramolecular aldol reaction. Use should use “H-B” for the Brønsted acid catalyst and “B “ for its conjugate base./02aOOCH3Hcatalytic acidOHHO(a) structure of the required nucleophile (mechanism not needed)(b) mechanism for the aldol reactionOHHO(c) structure for the subsequent aldol condensation product2310OHOCH2HOHOCH2HHBOHOCH2HHOHHOHB:protonation = 2 ptsintermediate 1 = 2 ptsaddition mech = 2