Strained Molecules in Organic Synthesis

Transcription

1 Strained Molecules in rganic Synthesis 0. Introduction ~ featuring on three-membered rings ~ Tatsuya itabaru (M) Lit. Seminar for cyclobutadienes : see Mr. Yamatsugu's Lit. Sem. 069 eat of Formation C + (gas) 6C + 6 (gas) cyclopropane methylenecyclopropane -methylcyclopropene SE = 7.5 kcal/mol SE = 0.9 kcal/mol SE = 5. kcal/mol cyclopropane +.7 kcal/mol cyclohexane kcal/mol The introduction of each trigonal carbon center into a threemembered ring introduces an additional - kcal/mol of ring strain. stable up to 00 C Strain Energy (SE) :.7 - (-9.6/) = 7.5 kcal/mol (cf. cyclobutane : 6.5 kcal/mol) s: 8%, p:8% 0 s: %, p:68% orbital of cycloproane Contents. Cyclopropenes. Asymmetric Synthesis of Cyclopropenes. chanism Study of Catalysis. ing Expansion [ to 5]. thylenecyclopropanes. ing Expansion [ to ]. [ + ] Cycloaddition & Theoretical Study. Intramolecular Cycloaddition Isocalysterol /0

2 . Cyclopropenes -. Asymmetric Synthesis of Cyclopropenes Scheme h catalyzed cyclopropenation Y hν base h L n Y h h carbenoid hν base Various etrosysnthesis of Cyclopropenes Doyle et al. JACS, 99,, 755 heat h (5-MEPY) Y alkyne about h catalyzed C- activation; see Mr. Yamaguchi & Tanaka Lit. Sem & Figure ' + diazoacetate -alkyne h (5-MEPY) ( mol %) C Cl C ' cyclopropene ()-bezyloxazolidinone (S)-isopropyloxazolidinone same condition 5% ee 6% ee It seems that dipolar influences from h (5-MEPY) ligand's carboxylate substituents are primary determinants of enatiocontrol in these reacton. Carbene dimer is major byproduct. Slow addition & higher aklyne ratio suppress it. In reactions with methyldiazoacetate, intramolecular C- insertion compete with cyclopropanation. h Scheme disubstituted alkynes /0 d-menthyl CC Et + TMS t Bu h (5-MEPY) y. 9% 6% ee y. 6% 0% ee

3 Doyle, Muller and Shapiro, JACS, 99, 6, 89 CCZ + (0 eq) catalyst cyclopropene Davies, L, 00, 6, Ar C donor/acceptor type > stability quarternally carbon center forming catalyst C acceptor type The donor/acceptor-type carbenoids are more stabilizedthan the conventional carbenoids derived from diazoacetate. substituent on alkyne substituent on diazoacetate The reactions proceed without regard to EWG or EDG. Too stable to react...? Cyclopropenation is favored over benzylic C- insertion. Cyclopropenation precede cyclopropanation. This substrate reacts with styrene and gives 90% ee. Then the failure may be due to the instability of the product. Table Electron rich alkynes react faster than normal alkyne. Does the reaction mechanism have a close relation to electron density of alkynes? /0

4 -. chanism Study of Catalysis Electron rich alkynes react faster. Stabilized cationic species at transition state concern...? The author proposed that the alkynes and olefins react by side-on mannar. For olefins, the reaction proceeds with retention of stereochemistry. Davies, JACS, 996, 8, 6897 alkyne olefin Side-on model cis trans EWG EWG δ+ δ+ h h sterically hindered ovel Catalyst Corey, JACS, 00, 6, 896 h L (Ac) h L h L ( t BuC ) Tf h h achiral space Figure > the upper right activity quadrant is achiral 0 however... + CC Et cat. cat. (0.5mol%) Ch Cl, rt y. 8% 99%ee + C Et (~:) C Et 9%ee cat. 86% ee cat. 0 9% ee 80% ee 88% ee cat. 0 97%ee The rate determing step is nucleophilic addition of diazoacetate to h L. high face-selectivity for carbenoid low(only :) π-facial selectivity or 9%ee Scheme. available for C- insertion C /0 cat. (mol%) C Cl, rt C y. 5%, ee. 96% Figure

5 Theoretical calculation tribridged carbenoid C h A h C Let A exist....5 kcal/mol higher Figure than tetrabridged one Figure B Davies, JACS, 00, 5, 590 Singleton, JACS, 005, 7, 690 If 6 reacts... Pr h C enyne metathesis C Pr h Pr + h L C End-on model Figure Corey et al. JACS, 005, 7, C( C) + CC Et C Et Pen h (Ac) (DPTI) h (Ac)(DPTI) h (DPTI) They can't synthesize. 5/0

6 -. ing Expansion [ to 5] Ma, JACS, 00, 5, 86 Battiste, TL, 975,, 5. thylenecyclopropanes (MCPs) -. ing Expansion [ to ] Furstner et al, JACS, 006, 8, 606 > 97% D-labeled [,] rearr. hydrogen shift For entry and, high concentration causes dimerization. Alkyl substituted MCPs also undergo ring expansion. 6/0

7 Shi, JACS, 006, 8, 70 are aromatic substituents. Substrates which have EDG at orthoposition give better yield. When are aklyl substituents, reaction doesn't proceed. -. [ + ] Cycloaddition & Theoretical Study Scheme. Thermal [+] cycloaddition C tal catalyzed hetero [+] cycloaddition Scheme a b trimethylenemethane (see Mr. agawa's Lit. Sem.) Lautens, JACS, 996, 8, 9597 from previous studies... t Bu Bn C 80 C, C, reflux Ar C, reflux E. akamura, JACS, 989,, 785 JC, 990, 55, 555 JC, 998, 6, 69 i 0 :. parent MCP undergoes proximal ring opening. monosubstituted MCPs undergo proximal and distal ring opening. MCPs which bear dialkyl substituents at cyclopropyl or vinylic carbon undergo distal ring opening preferentially 0 : all types of MCPs undergo distall ring opening regardless of the substitution pattern 9% t Bu Bn 86% (96:) C 9% oyori, JACS, 970, 9, 5780 & TL, 978,8, 8 Scheme 5 i(c) i(cd) : proximal attack (A) with phosphine or phosphite : distal attack (B) i(c) : distal attack (B) Scheme 6 96a 96b 7/0

8 Theoretical Study of Insertion & [+] Cycloaddition chanisms Scheme Fujimoto et al, Inorg. Chem. 996, 5, Inorg. Chem. 000, 9, Theoretical works on d 0 matal-tmm have revealed that L TMS Ac they have a zwitterionic charge distribution. Experimental results support this mechanism: TMM-L stepwise complexes demand that olefin has electron-deficient groups. n the other hand... MCP- complexes react both with electron-rich olefins and electron-poor olefins. Scheme + L distal bond insertion Path P Path Path Path Path η (with MCP) mechanism Path P proximal bond insertion Path Path 5 P Path Path (TS) (TS) /

9 catalyzed [+] cycloaddition of aldehydes and imines Y. Yamamoto et al. ACIE, 00, 0, 7 Y. Yamamoto et al. TL, 00,, 60 ther, Pt sources didn't catalyze the reaction. additive: P, PBu, P() slow and low yield Table no reaction additive: P, P t Bu, P(o-tolyl) good to high yield bidentate ligands trace solvent: TF, C, Diox, DMF good to moderate yield C Cl no reaction 0 ther eactions Ma, JACS, 00, 6, 965 distal bond insertion γ β α Figure Proposed mechanism Scheme =, Ts Shi, Chem. Eur. J., 006,, 50 9/0

10 Y. Yamamoto, JC, 00, 69, 0 Scheme γ β rigid different reaction position α These heteroaromatics can't make rigid coordination to. Then reactions don't proceed (at all). A B y. 5 ~ 6% ~ 9% 6% 0 no reaction no reaction TMS Ac 0 A or B?? complicated mixture of unidentified products -. Intramolecular Cycloaddition E. akamura, Tetrahedron, 989, 5, 088 Motherwell, TL, 989, 0, 707 Scheme retention Table bicyclo [,,0] anti-bredt rule bicyclo [,,0] Lautens, JACS, 996, 8, 9597 Table Substitution at and have little effect on stereoselectivity. Table Table Scheme E E E 5 Si subsutituted alkynes also didn't cyclize. E E 0/0