James A. Marshall

SE' Addition of homochiral α-alkoxyallylstannanes to aldehydes

Abstract Addition of the homochiral ( S )-[1-(benzyloxy)methoxy-2-( E )-hexenyl] (tri- n -butyl) stannane (5b) to heptanal (1a), ( E )-2-heptenal (1b), and 2-heptynal (1c) under BF 3 catalysis was examined. In all cases the addition proceeded by anti S E , attack to give mainly the syn E adducts se8a-c with high ee.

Synthesis of homochiral α-alkoxystannanes: stereospecific conversion to cembranolide precursors

Stannyl ketone 3 is reduced rapidly and with high stereoselectivity to the (S)-alcohol 4 by Noyoris (R)-(+)-BINAL-H reagent. The derived MOM ether aldehyde cyclizes upon treatment with BF3•Et2O affording the cis alcohol 8 as a single enantiomer.

The Wittig Rearrangement

In 1942 Wittig and Lohmann described the isomerization of α-lithiated ethers (2; Rxa0=xa0Me or CH2Ph) to skeletally rearranged lithio alkoxides (3; equation 1).1 Subsequent work by Wittig and others established that a variety of ethers undergo the Wittig rearrangement, provided the α-anion is stabilized by an aryl substituent. Of the several mechanisms proposed for this reaction a sequence involving homolysis of the anion intermediate (5), followed by recombination of the radical and radical anion fragments (equation 2) best accommodates the experimental findings.1–4

Stereoselective SN2' additions of organocuprates to homochiral acyclic vinyloxiranes

Abstract Additions of various methylcopper reagents to the homochiral acyclic vinyloxiranes A14, A15, B6–B9, and C5, C6 were performed in order to evaluate E/Z and syn/anti preferences. The unsubstituted oxiranes A14 and A15 gave a mixture of SN2 and SN2 substitution products with the four reagents examined, LiMe2Cu, LiMeCuCN, BrMgMe2Cu, and LiMeCuI · BF3. The more highly substituted systems B6–B9 derived from geraniol and C5, C6 derived from nerol yielded only SN2 products. The (Z)-allylic alcohol derivatives B8 and C6 and LiMeCuCN gave the best anti/syn ratios (99:1 and 97:3, respectively). In both cases the newly formed double bond was exclusively E.

Synthesis of nonracemic y-alkoxy allylstannanes by stereospecific anti[1,3]-stannyl migration

Abstract The y-alkoxy allylstannane 5b , prepared in high yield by BF 3 · OEt 2 promoted [1,3] rearrangement of the ( S )-α-alkoxy allylstannane 4b , affords the syn 1,2-diol derivatives 8 and 9 in high yield and excellent ee upon condensation with various aldehydes.

Cembranolide total synthesis. Anisomelic acid

Abstract The stereoselective total synthesis of (±)-anisomelic acid ( 34 ) has been achieved starting from aldehyde 7 , the ozonolysis product of geranyl acetate. Two key steps ensured the stereoselectivity of the synthesis. The first entailed a highly anti-selective addition of the allyltitanium derived from carbamate 15 to aldehyde 5 affording the enol carbamate allylic alcohol 16 . The second was a highly ( Z )-selective Horner-Emmons cyclization of the derived phosphono ester aldehyde 25 leading to the conjugated ester 27 . Further conversion led to the crystalline lactone 30 whose structure was confirmed through single crystal X-ray analysis. Equilibration of the conjugated double bond of 30 gave rise to a 1:1 mixture of the ( Z ) and ( E ) isomers. This result was foretold by molecular mechanics calculations.

Enantioselective [2,3] Wittig ring contraction induced by chiral bases: the total synthesis and absolute configuration of (+)-aristolactone

Abstract [2,3] Wittig ring contraction of the achiral 13-membered acetylenic ether 1 via treatment with lithio (R,R) or (S,S)-bis-(1-phenylethyl)amide afforded the (R)-(+) or (S)-(-)-propargylic alcohol (+)-2 or (-)-2, respectively, of > 60% ee in 75% yield.

Total synthesis of the germacranolide (±)-aristolactone via [2,3] Wittig ring contraction

The total synthesis of (±)-aristolactone (15) is described wherein the key cyclodecenynol precursor 10 is prepared in over 90% yield via a highly regio and stereoselective [2,3] Wittig rearrangement of the 13-membered propargylic ether 9.

Stereoselective cyclization of α-alkoxyallylstannane alkynals and their Co-complexes. A new route to cyclododecyne-1,2-diol derivatives

Abstract The α-alkoxyallylstannane dicobalt hexacarbonyl alkynal complex 18 afforded the cyclododecadienyne alcohol complex 19 as a single diastereoisomer in 70% yield upon treatment with BF 3 ⊎ Et 2 O at −78°C. The reaction is thought to proceed by prior isomerization to the γ-alkoxyallylstannane.

Diels-alder cyclization of 2,8,10-undecatrienals as a route to 1,2,3,4,4a,5,6,8a-octahydronaphthalenes

Abstract 2,8,10-Undecatrienals have been found to undergo facile Diels-Alder cyclization upon treatment with alkylaluminum chlorides in methylene chloride at low temperature. The reaction is highly endo-selective. Protected alcohol substituents at the C-4 and C-7 positions are fully accommodated and TBDMS protected alcohols show a strong axial preference. The methodology has been applied to a hydronaphthalenecarboxylic add of possible use in a projected total synthesis of the macrocyclic antitumor antibiotic, chlorothricolide.