TBS deprotection

Glycosylation between glucosaminyl donor 147 and inositol acceptor 148 followed by Ir-catalyzed deallylation provided the pseudodisaccharide core 149 (Scheme 13.22). It was coupled to the phosphoglycerolipid derivative 150 with the use of 17/-tetrazolc as mild acidic promoter and then oxidized with iBuOOH at low temperature to avoid epoxidation of the unsaturated lipid. The phosphoglycerolipidated pseudodisaccharide then underwent TBS deprotection to afford the desired 4 -alcohol 151. 

The alkyne is transformed into the corresponding organotin reagent by radical hydrostannylation. First under kinetic control the Z-organo-stannane is formed. But in the presence of excess tributyltinhydride, reversible addition of the tributyltinradical to either carbon atom of the double bond equilibrates the Z-isomer to the more stable -organo-stannane, which is obtained in 53 % (2 steps). TBS- deprotection furnishes 23 (building block II) in 63 % yield. When hydrostannylation and deprotection are carried out the other way round, the yield of this sequence from 20 to 23 drops from 33 % to 29 %. 

In six more steps alkyne 22 is transformed into sulfone 24 (building block III) for the final coupling reaction. These steps include TBS deprotection (75 %, over 2 steps from 20), palladium-catalyzed addition to methoxy tetrolate (61 %), DIBAL reduction (91 %), Mukaiyama redox condensation (86 %), acetylation (97 %) and (NH4)6Mo7024-catalyzed oxidation with H2O2 (99 %). 

Starting from (+)-diethyl tartrate (2), bromobutenolide 18 was obtained in nine steps. Three of the four C=C double bonds were built up using a Wittig reaction (11—>12), an Ando- y Q Horner-Wadsworth-Emmons reaction (13— 15) and (3-elimination (16 18). From (-)-actinol (3) stannane 23 and sulfone 24 were synthesized in 9 and 13 steps, respectively. Their common intermediate, alkyne 22, was synthesized using methoxycarbonylation. Sharpless asymmetric epoxidation and Ci-elongation with lithio trimethylsilyldiazomethane. Stannane 23 was obtained upon hydrostannylation and TBS deprotection. Sulfone 24 was obtained after addition to methyl tetrolate, reduction, Mukaiyama redox condensation, acetylation and catalytic oxidation. 

As outlined in Scheme 9, the 1,6-wawwo-trisaccharide 9.8 was prepared from enone 9.2 with a C-6 OTBS group. The synthesis was accomplished by a simple glycosylation/TBS-deprotection strategy to prepare first a disaccharide 9.4 and then trisaccharide 9.5 by repeating the two steps. The manno stereochemistry of 9.8 was installed by a one pot NaBH4 reduction and one-pot dihydroxylation of 9.5. Thus, in only these two steps, nine stereocenters were... 

Using an oxidation/reduction sequence the g/wco-papulacandin 5.11 was also produced from 5.8. The dihydroxylation product of 5.8 was selectively protected at C-3 and the C-2 axial alcohol was oxidized (Dess-Martin) and reduced (DibalH) to intall the g/wco-stereochemistry, which upon TBS-deprotection give the gluco-isomer 5.11. 

Straightforward reactions. The next crucial step was an unprecedented introduction of the chlorodiene. Coupling of the allylindium reagent with aldehyde 515 afforded two homoallylic alcohols, which were dehydrated with Martin s sul-furane to afford exclusively the traws-chlorodiene. TBS deprotection followed by Swem oxidation gave aldehyde 516. 

An alternative route by the Danishefsky group was developed [142e-g] (Scheme 84). The aldol reaction of ethyl ketone 580, prepared from P-keto ester 579, with aldehyde 581 stereoselectively afforded 582 (dr = 5.4 1). After Troc protection followed by hydrolysis of the enol ether, Suzuki coupling with 583 followed by TBS deprotection gave the desired (12Z)-olefin 584. The Noyori reduction of the P-keto ester 584 gave 3a-alcohol with high stereoselectivity, which was converted into hydroxy carboxylic acid 585. Macrolactonization of 585 was accomplished by the Yamaguchi method, and subsequent deprotection and DMDO oxidation efficiently afforded epothilone B (5b). 

Following this historical precedent, a sulfone was readily appended onto the diene system of 37, affording 38 in 91 % yield (Scheme 7). One should note that in this transformation both isomers obtained from the prior Wittig olefination were employed, resulting in the mixture of stereoisomers at C-9 in 38. Based on the assumption that eventual thermal extrusion of SO2 from either diastereomer would provide the requisite trans-substituted olefin in the diene desired for Diels—Alder reaction, this lack of selectivity was not deemed problematic. However, the pressing issue at this juncture remained the generation of the quinone. Fortunately, with the diene now protected, oxidative demethylation smoothly furnished 39 in 79 % yield with concomitant TBS deprotection. 

Under enyne cross-metathesis conditions, the intermolecular reaction of the a,(D-dienes 153, derived from the MBH reaction, with different terminal alkynes 154 afforded triene intermediates that cyclized spontaneously under the reaction conditions to give substituted cis-hexahydro-l/f-indenes 155 (Scheme 4.45), which can be further transformed into steroid analogues via TBS deprotection and oxidation. However, metathesis reactions starting with 156 only furnished trienes 157 [as EfZ) mixtures] and no spontaneous intramolecular cycloaddition occurred. Even at elevated reaction temperatures, trienes 157 cyclized only slowly to give octahydronaphthalene diastereomers. With deprotection of the TBS and subsequent Dess-Martin oxidation, trienes 157 could be converted exclusively into cw-fused 7-substituted 6,7-dehy-drodealone-l-one-lO-carboxylic esters 158 in 50-60% yields. Moreover, c ross-metathesis of TBS-unprotected MBH adduct 159 with alkynes 154 along with treatment with Dess-Martin periodinane (DMP) in one pot could conveniently produce the corresponding bicyclic ketones 160 in moderate yields. ... 

The synthesis of unique seven-membered ring sultams has been reported, by an intramolecular oxa-Michael addition reaction from vinyl sulfonamides 248 via a one-step or two-step method, both of which give similar yields of sultams, 249 (13T2369).The intramolecular oxa-Michael reaction was initiated by either TBS-deprotection (with TBAF) to form alkoxide intermediates (Method A), or by removal of the protecting group by HCl to give vinyl sulfonamide alcohols which, upon reaction with NaH, the oxa-Michael reaction is initiated (Method B). 

To avoid decomposition of the sensitive 2-hydroxy azide side chain with Lewis acid, the azide functional group was reduced to amine. These conditions also deprotected the carboxy terminus. After TBS deprotection in acidic conditions, the 2-amino alcohol was treated with excess BBtj for deprotection of Cbz (benzyloxycarbonyl) and OMe groups. Synthesis of biphenomycin B 53 was completed in 14 steps affording 15% overall isolated yield. 

Compound 69 upon Boc deprotection, Af-allyaltion followed by ring-closing metathesis provides the compound 70, which upon asymmetric dihydroxylation and TBS deprotection provides (—)-swainsonine... 

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